Internal Medicine: Open Access

Internal Medicine: Open Access
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Research Article - (2021)Volume 11, Issue 4

Availability and Use of Long-Acting Insulin Analogues Including Their Biosimilars across Africa: Findings and Implications

Brian Godman1,2,3*, Trudy Leong4, Abdullahi Rabiu Abubakar5, Amanj Kurdi1,6, Francis Kalemeera7, Godfrey Mutashambara Rwegerera8,9, Okwen Patrick10,11, Loveline Lum Niba10,12, Kamilou Ibrahim13, Adefolarin A Amu14, Patrick Matowa14, Joseph Acolatse15, Robert Incoom15, Israel Abebrese Sefah16,17, Sylvia Opanga18, Lisper Wangeci Njeri19, David Kimonge18, Margaret Oluka20, Ibrahim Chikowe21, Felix Khuluza21, Henry Phiri22, Dan Kibuule7, Ester Hango7, Ibrahim Haruna Sani23, Oliver Ombeva Malande24,25, Thereza Piloya-Were26, Luke Alutuli27, Aubrey Chichonyi Kalungia28, Blessmore Vimbai Chaibva29, Trust Zaranyika30, Mainul Haque31, Eleonora Allocati32, Stephen Campbell33,34, Eunice Twumwaa Adwubi35 and Olayinka O. Ogunleye36,37
 
*Correspondence: Brian Godman, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, United Kingdom, Tel: 0141 548 3825, Fax: 0141 552 2562, Email:

Author info »

Abstract

Background: Prevalence rates of diabetes mellitus are growing across Africa with an appreciable number likely to be on insulin to manage their condition. This has significant implications on future morbidity and mortality exacerbated by high complication rates. Complication rates in patients requiring insulins are enhanced by hypoglycaemia. Long acting insulin analogues were developed to reduce hypoglycaemia and improve patient compliance. However, they are typically appreciably more expensive than human and other insulins in Africa, and continuing controversies surrounding their benefits limits their listing on national Essential Medicine Lists (EMLs). Biosimilars can reduce the prices long-acting insulin analogues. This needs assessing.

Methods: Mixed methods approach including documentation of insulin utilisation patterns and prices among a range of African countries. In addition, input from senior level government, academic, and healthcare professionals from across Africa on the current situation with long-acting insulin analogues as well as potential changes needed to enhance future funding of long-acting analogue biosimilars.

Results: There is variable listing of long-acting insulin analogues on national EMLs across Africa due to their high prices and issues of affordability. Even when listed, utilisation of long-acting insulin analogues is limited by similar issues including affordability. Appreciably lowering the prices of long-acting insulin analogues via biosimilars should enhance future listing on EMLs and use accompanied by educational and other initiatives. However, this will require increased competition to lower prices.

Conclusion: There are concerns with value and funding of long-acting insulin analogues across Africa including biosimilars. A number of activities have been identified to improve future funding and listing on EMLs.

Keywords

Africa; Long-acting insulin analogue biosimilars; Cross-national study; Diabetes; Drug Utilization; Essential Medicines List; Health Policy; Insulin glargine; Prices

Introduction

We have seen incident and prevalence rates of diabetes mellitus grow across countries, with this trend continuing [1,2]. Global incident cases rose to 22.94 million in 2017, rising by more than 100% since 1990 [1]. Overall in 2019, there were 463 million people with diabetes mellitus worldwide, with an appreciable number from Low- and Middle-Income Countries (LMICs) [3]. Across Africa, there is an estimated 15.9 to 19 million with diabetes mellitus, with prevalence rates likely to reach 34.2 million in sub- Saharan Africa by 2040, and potentially up to 42 to 47 million across Africa by 2045 [4-6]. We have also seen high prevalence rates for patients with diabetes among individual African countries [4,7]. For instance in Ghana, an estimated 6.46% of the adult population have diabetes mellitus. However, this is likely to be an appreciable under-estimation with a significant number of people with diabetes undiagnosed due to a lack of awareness of their condition [8,9]. In Malawi, the prevalence of NCDs, including diabetes, hypertension, and obesity, is rising similar to other African countries [7,10]. Recent estimates suggest prevalence rates for patients with diabetes in Malawi range from 2.4% to 5.6% of the population, with prevalence rates expected to rise further unless addressed, with similar rates in Zambia at 4.2% of the population and rising [11,12]. Prevalence rates are higher in Uganda with 10.1% of the population estimated to have diabetes and growing [13]. Whilst diabetes is predominantly Type 2 Diabetes (T2DM) across Africa, up to 35% or more of patients with diabetes in LMICs, including those in Africa, require insulin, either alone or in combination with oral therapies, to manage their condition [14-17].

Growing prevalence rates will increase the worldwide economic burden of diabetes mellitus to between US$2.1 to US$2.5 trillion by 2030, which includes both direct and indirect costs, equating to 2.2% of Gross Domestic Product (GDP) [18]. There is also a considerable economic burden due to diabetes mellitus across Africa, which reflects a general increase in Non-Communicable Diseases (NCDs) across the continent [19]. NCDs include Coronary Vascular Diseases (CVD) and diabetes, with morbidity and mortality associated with NCDs likely to exceed those associated with infectious diseases in Africa by 2030 [6,20-24].

In 2015, the cost of diabetes mellitus in sub-Saharan Africa, including both direct and indirect costs, was estimated at US$19·45 billion, equating to 1.2% of GDP, with the majority being direct costs including the costs of medicines [23]. These costs are estimated to increase to between US$35·33 billion and US$59·32 billion (1.1% to 1.8% GDP) by 2030 unless addressed, with the costs associated with diabetes mellitus enhanced by the complications of poor glycaemic control and associated co-morbidities [23]. Complications include renal disease, potentially leading to dialysis and transplantations, diabetic feet ulcerations resulting in lower extremity amputations, complications with the eyes leading to blindness, as well as a greater risk of heart attacks and strokes [3]. These complications appreciably increase hospitalisation costs among patients with diabetes in Africa, which is a growing concern [25].

As a consequence of the growing prevalence rates coupled with increasing complication rates, diabetes mellitus is known to be among one of the top three causes of outpatient morbidity in primary healthcare facilities in Ghana [26]. There are also concerns generally with the management of patients with diabetes mellitus across Africa, including South Africa. These include addressing high rates of hypoglycaemia as well as adherence to treatments to decrease associated morbidity and mortality, with community-based projects potentially helping to address key issues of identification and management [27-29]. Overall, diabetes mellitus is seen as a leading cause for CVD, disability, and death across sub-Saharan Africa, alongside reducing the quality of life of patients; consequently, needs to be carefully managed [7,23,30-32]. Rising rates of NCDs, including diabetes mellitus, among Southern African countries have also been linked with increased aged standardised mortality rates [33].

We have previously documented potential ways to improve the management of patients with both Type 1 Diabetes Mellitus (T1DM) and T2DM across Africa given the increasing burden and the resultant implications [4,7]. Ways forward included enhancing the availability of medicines including insulins as well as equipment and facilities to improve early diagnosis and monitoring of blood glucose levels at home [2,7,17,34-36]. We are aware that the availability and affordability of medicines to treat patients with diabetes mellitus, especially insulin, can be a key issue among African countries, similar to other LMICs, exacerbated in the case of insulin by three principal manufacturers globally accounting for up to 96% of the global market by volume and up to 99% by value [37-44]. This is highlighted in the studies by the ACCISS (Addressing the Challenge and Constraints of Insulin Sources and Supply) group and others documenting the key challenges globally with limited competition generally surrounding the availability and affordability of insulins especially in LMICs [42,43,45]. There are though ongoing initiatives to enhance competition among manufacturers to help lower insulin prices. These include the WHO prequalification initiative, which is expected to increase the flow of quality-assured insulins thereby potentially providing countries, especially LMICs, with a greater choice of insulins and patients with lower prices [41,46]. This builds on a number of initiatives among African countries to enhance access and availability of insulins.

In Cameroon, the Changing Diabetes in Children’s (CDiC) initiative was launched in 2010 in conjunction with the International Diabetes Federation and local governments to offer free diabetes care to children and adolescents with T1DM as access and availability of medicines including insulins, as well as monitoring equipment, was a major issue [47-49]. This included a range of free insulins, namely regular insulins (Actrapid®), intermediate-acting insulins (Insulatard®) and pre-mixed insulins (Mixtard 30®) [48].

In Kenya, concerns with high rates of undiagnosed diabetes, which can be as high as 60% of those patients with diabetes, as well as issues of affordability of medicines especially among diabetes patients with co-morbidities, has resulted in a number of initiatives to try and address these issues [7,50-52]. This includes the Base of Pyramid (BoP) project, which aimed to enhance diagnosis as well as establish a ceiling price of KSh 500–600 (US$5) for insulin Mixtard® 1000IU (10mls 100IU/ml) in participating healthcare facilities, surrounding markets and private pharmacies. As a result, enhance the affordability of medicines for patients with diabetes including insulin given current high co-payment levels [51]. This equates up to a two-thirds price reduction [51].

Patient illnesses can have catastrophic consequences for families in Nigeria and other African countries where there are high patient copayments; consequently, treatments should be carefully considered before being prescribed [53,54]. This is particularly important in Nigeria where published studies have shown that the costs of medicines to treat patients with diabetes can range from 72.3% to 90% of total costs, much of which will be out-of-pocket [55,56]. The situation may ease among children with diabetes in Nigeria with Novo Nordisk seeking to offer insulin free to children during 2021 similar to the CDiC initiative in Cameroon [57].

In Tanzania, studies have found that the different types of insulin were only available in public health facilities on a limited number of occasions, e.g., 8% to 17% of occasions, with other studies showing that stock-out of insulins and other key medicines for patients with diabetes is a frequent occurrence in the country, which is a concern with affordability a key issue in Tanzania [30,58,37]. There are ongoing initiatives to address this including the Christian Social Services Commission (CSSC) and Biocon recently signing a memorandum of understanding to take part in a pan-African project entitled ‘Mission 10 cents’. Within this project, insulins, including recombinant human insulin (rh-insulin), will be sold at a cost of less than 10 US cents per day, with Tanzania potentially a pilot for other African countries. This is beneficial given the potential impact of the cost of insulin on African families without universal healthcare [59,46].

There are also concerns with the lack of consumables to monitor blood glucose levels across a number of African countries including Zimbabwe, with the cost of tests a deterrent to their use among patients with diabetes attending public healthcare institutions potentially compromising their care [7]. This needs to be addressed going forward to reduce future morbidity and mortality associated with diabetes across Africa.

As mentioned, there are issues with adherence to prescribed medicines among patients with diabetes across Africa [27,60-63]. These concerns increase the need to improve the management of patients with diabetes mellitus and associated CVD across Africa to further reduce future morbidity and mortality [64]. This includes improving glycaemic control and reducing rates of hypoglycaemia, which is a concern as hypoglycaemia is one of the most feared issues associated with diabetes, enhanced by the lack of consumables to monitor blood glucose levels across Africa [28,36,65,66,7].

Long-acting insulin analogues were developed to reduce the risk of hypoglycaemia, especially nocturnal hypoglycaemia. Alongside this, provide greater convenience to patients given the reduced number of injections, with improved convenience enhancing compliance, resulting in improved outcomes including reduced hypoglycaemia and its consequences [3,67-74]. As a result, we are now seeing the utilisation of long-acting insulin analogues exceeding that of human insulins among upper-middle and high-income countries, reflected in worldwide sales of long-acting insulin glargine at US$3.88 billion in 2018, potentially rising to US$9.26 billion by 2025 [39,75]. Concurrent with this, worldwide sales of long-acting insulin detemir were US$2.7 billion in 2015 and growing at 7.5% per year [76].

However, Hemmingsen et al. (2021) in a recent systematic review of long-acting insulin analogues in T1DM found that long-acting insulin analogues did not show any patient benefits, or harms, for severe nocturnal hypoglycaemia versus Neutral Protamine Hagedorn (NPH) insulin [77]. These authors also found no true beneficial or harmful effect for long-acting insulin analogues in other measures [77]. More recently though in a systematic review combined with a network analysis, Tricco et al. (2021) found that long-acting insulin analogues led to fewer major or serious hypoglycaemic (OR 0.63) or nocturnal hypoglycaemic episodes (OR 0.74) as well as a reduced HbA1c levels (mean difference -0.14 percentage points) [78]. This is a key issue given ongoing concerns with the value of long-acting insulin analogues versus NPH and other insulins among LMICs in view of their appreciably higher costs, which has resulted in calls for disinvestment in some LMICs [79-82]. We are also aware that most studies involving long-acting insulin analogues have been conducted in higher- versus lowerincome countries where the dynamics of the populations can be very different especially surrounding access and availability of medicines [39,83].

Alongside this, Ewen et al. (2019) showed there was a considerable price difference between human insulins (US$5 per 1000 IU) and long-acting insulin analogues (US$33/1000IU) affecting their funding and use among a range of LMICs [39]. However, a number of studies have now shown that the higher acquisition costs of long-acting insulin analogues can potentially be offset by savings from averted costs of hypoglycaemia and other diabetes-associated complications, although this is not always the case [72,73,84-88]. Consequently, further research is needed among patients with diabetes mellitus across Africa to determine the extent to which long-acting insulin analogues reduce the risk of long-term diabetic complications in practice to enhance their potential for funding alongside possible price reductions with the advent of biosimilars given current considerable differences in prices [39]. We are aware following the availability of biosimilars such as biosimilar infliximab and biosimilar adalimumab that they can appreciably lower the cost of biologic medicines and enhance their use as seen with adalimumab in Denmark where expenditure was reduced by 82.8% following the availability of biosimilars, with the cost of insulin glargine also appreciably reduced in Bangladesh following biosimilars [89-92].

In view of the ongoing controversies and issues surrounding longacting insulin analogues, including higher costs, these are currently not included in the World Health Organization Essential Medicines List (WHO EML) [93]. This is despite their growing use in a number of upper-middle and higher-income countries including European countries [39,94,]. Although, there is variable use among lower-income countries [39]. In Bangladesh, only NPH and other similar insulins are funded in public hospitals whilst there is 100% co-payment for long-acting insulin analogues, similar to parts of India [39,92]. However, there is growing use of long-acting insulin analogues in ambulatory care in Bangladesh in view of their perceived benefits, which is increasingly biosimilar insulin glargine under the guidance of physicians [92]. Long-acting insulin analogues are also currently not funded within the public healthcare systems in South Africa and Zambia due again to concerns with higher costs than NPH insulins and other similar insulins with no perceived clinical advantage [96,97]. Long-acting insulin analogues are though listed in the EMLs of Kenya, Namibia and Zimbabwe along with other African countries [7,98-100]. However, there can be issues of affordability limiting their prescribing [100].

We are aware, as mentioned, that the availability of biosimilars can appreciably lower the cost of biologic medicines and enhance their use [89,90]. There have though been concerns regarding limited price reductions to date for biosimilars of long-acting insulin glargine including among some LMICs, along with price reductions by the originator company, impacting on their funding and use in practice [39,95,101,102].

As a result, we believe there is a need to re-assess current utilisation and expenditure patterns for insulins, including long-acting insulin analogues and their rationale across Africa. This includes potential ways to reimburse and fund long-acting insulin analogues such as insulin glargine and insulin detemir within public healthcare systems across Africa including their incorporation into national EMLs and Standard Treatment Guidelines (STGs) given increasing recognition of their value and use among higher-income countries [3,39,94]. However, this needs to be balanced against the recent findings of Hemmingsen et al. (2021) [77]. In addition, investigate potential prices for the different insulins among the different African public healthcare systems where available. Alongside this, investigate possible price reductions for long-acting insulin analogues via biosimilars to enhance their funding within public healthcare systems. These are the objectives of this paper, which build on our recently published studies regarding the management of diabetes mellitus across Africa as well as those conducted by Ewen et al. (2019) [4,7,39].

Methodology

We adopted a mixed methods approach. This included information from the co-authors, who are a mixture of senior-level personnel from governments and their advisers, clinicians, academia, and rational medicine use advisers, from across Africa to provide information on the current situation regarding long-acting insulin analogues within the public healthcare system in their country, i.e., whether listed in the EML or STGs in their country. In addition, potential solutions to encourage funding and use of long-acting insulin analogues if currently not listed or funded within their country. This includes the extent of potential prices and price reductions for long-acting insulin analogues to enhance their listing with national EMLs through biosimilars for insulin glargine as the first biosimilar for long-acting insulin analogues available across countries [95]. This builds on our two recent papers regarding the management of patients with diabetes across Africa as well as the use of long-acting insulin analogues within a limited number of African countries [4,7,100,103].

With respect to biosimilars, we will only be interested in biosimilars of long-acting insulin analogues given the current controversies surrounding their use including appreciably higher prices than NPH and other insulins [39]. Patterns of current insulin use within the country will though be documented where such data sets are available to provide a background for the current situation across Africa. This will typically be data from hospitals as currently there is generally no national comprehensive data available for the public healthcare system among a number of African countries, which is unlike the situation across Europe [104-106]. This is similar to the approach among a number of Asian countries [92,107]. We will though be using national data sets in South Africa. Utilisation data will be converted into Defined Daily Doses (DDDs) for comparative purposes where pertinent similar to other studies alternatively, kept as pack data. The DDDs have been based on a DDD of 40 for insulin, e.g. the DDD for soluble human insulin 100IU/3ml cartridge is 7.5 DDDs (300/40) [104,105,108,109].

We will also collect data on the utilisation and prices of long-acting insulin analogues from community pharmacies and drug stores in Nigeria since patients typically purchase their medicines from such stores [103]. This is similar to the methodology employed when assessing the impact of COVID-19 on utilisation and prices of pertinent medicines and equipment in Nigeria and other African countries in the months following the pandemic and similar to the recent studies across Asia including Bangladesh [110,111,92,107]. Prices where pertinent will be converted to US$ using current conversion rates for comparative purposes.

We did not collect data on mark-ups in pharmacies as our main objective in Nigeria and other pertinent African countries was to collect actual pricing and expenditure data. We are aware though that Ball et al. (2019) had collected data on pricing components of insulins in a number of LMICs including African countries, where cumulative mark-ups can range from 8.7% to 565.8% [112]. This is an important area, which we will comment on when discussing possible future activities across Africa to enhance usage and funding of long-acting insulin analogues.

We also did not collect experiences regarding the registration of insulins across Africa. We are aware though of the circulation of falsified and substandard antidiabetic medicines including insulin, with these manufacturers taking advantage of rising prevalence rates of diabetes across Africa, further compounded by the proliferation of internet run pharmacies that are not well regulated In LMICs [113]. However, steps are being taken to address such activities including the Lomé initiative placing falsified and substandard medicines on the highest political agenda in Africa with ongoing measures to strengthen the legal response to these medicines [114,115]. Alongside this, initiatives to accelerate mutual recognition for new medicines among African regions such as the West Africa Region [116]. These progammes are in addition to the current WHO prequalification initiative to enhance the availability of quality-assured and lower priced insulins to address issues of affordability among patients and governments [41,46].

Similar to our previous studies regarding the management of patients with diabetes across Africa, we will not split the African countries down into low- or middle-income African countries as a number of the issues surrounding the management of patients with diabetes mellitus appear similar across Africa [4,7]. This includes issues of affordability along with issues of diagnosis and regular monitoring of blood glucose levels [4,7]. However, we will break the participating African countries down into those that currently list and/or fund long-acting insulin analogues within their public healthcare systems and those that do not. This is because we believe the different African countries can learn from each other when it comes to suggesting potential ways forward to enhance listing and/ or funding of long-acting insulin analogues within their public healthcare systems. This will principally be originator long-acting insulin analogues unless stated as we and others have previously shown limited funding and utilisation of long-acting insulin analogues across Africa and with it likely limited availability and use of biosimilars of long-acting insulin analogues [7,39,103].

We will also investigate whether those African countries that do not list or fund long-acting insulin analogues routinely have lower GDP levels per head of population versus those African countries that list these insulins since issues of affordability and access could play a greater role in countries with low GDP/capita. We will use the latest data from the World Bank to document current rates [117].

We did not seek ethical approval as we were not dealing with patients, in line with national legislation and institutional guidelines [107,110,118]. Besides, the pharmacists taking part in the study freely provided the requested information having been allowed to refuse to participate if wished. This is in line with previous studies undertaken by the co-authors in related areas including analysis of policies to enhance the rational use of medicines and biosimilars, pricing policies and issues surrounding generics, which all involved direct contact with health authority personnel, healthcare professionals and other key stakeholders [4,7,90,104,105,119,].

Results

Typically among African countries, there is currently limited utilisation of long-acting insulin analogues in the public healthcare system, similar to our previous findings [7]. This is exacerbated by currently considerable cost differences between long-acting insulin analogues and the different human insulins, with a number of African countries currently struggling with resources and capacity, including personnel, to fund early diagnosis of diabetes as well as standard insulins such as NPH insulins and self-monitoring of blood glucose levels [7,37,121]. Furthermore, there is currently variable listing of long-acting insulin analogues within the EMLs of African countries [96,121].

Table 1, summarises typical insulins available across countries and those contained within the current WHO EML with Table 2, summarising the current situation regarding African countries that currently list long-acting insulin analogues within their EMLs and/or STGs and those that do not alongside current GDP/capita levels. The rationale for these findings is expanded within the synopsis for each country.

Classification Examples and associated brand names (where pertinent)
Sort-acting/ rapid-acting insulins Insulin Aspart
Insulin Lispro
Neutral insulin (Actrapid®)
Intermediate (NPH) insulin/ longer-acting insulins Human insulin isophane
Premixed human insulins Insulin isophane and insulin regular (Humulin® 70/30®)
30% insulin soluble and 70% isophane insulin (Mixtard 30®)
Long-acting insulin analogues Degludec
Detemir
Glargine
WHO EML (21st) Insulin injection (soluble)

Table 1: Different insulin preparations and their classification excluding ultra short acting [122,123].

Whilst the surveyed African countries with lower GDPs/capita tended not to list long-acting insulin analogues in their EMLs, this was by no means universal with the analogues not listed among three out of the four included African countries with the highest GDP/capita (Table 2).

Country GDP/ capita (US$)* Current listing of long-acting insulin analogues in EMLs
Listed in EML Not listed in EML
Malawi 625.3
Uganda 817
Zambia 1,050.90
Tanzania 1,076.50
Zimbabwe 1,128.20
Cameroon 1,499.40
Kenya 1,838.20
Nigeria 2,097.10
Ghana 2,328.50
Eswatini 3,415.50
Namibia 4,211.10
South Africa 5,090.70
Botswana 6,711.00

Table 2: Current GDP/capita and listing of long-acting insulin analogues in country EMLs across Africa.

African countries where long-acting analogues are funded/listed in the public healthcare system

Cameroon: Long-acting insulin analogues are available within the healthcare system of Cameroon, with patients with diabetes principally managed in ambulatory care [7]. However, access and availability of insulins, as well as monitoring equipment, is a major issue with high co-payment levels outside of sponsored programmers’ such as the ‘Changing Diabetes in Children’ (CDiC) initiative in conjunction with the International Diabetes Federation and local governments [17,47]. This is reflected by only Mixtard® and Actrapid®. Table 1, being dispensed within a leading ambulatory care facility in Cameroon, with overall expenditure within this facility rising over 2-fold between 2015 and 2019, with this trend likely to continue. Prices of long-acting insulin analogues will need to appreciably reduce with for instance biosimilar long-acting insulin analogues to address issues of affordability in Cameroon given current high co-payment levels, similar to other African countries [39].

Ghana: Two long-acting insulin analogues, insulin glargine and detemir, were approved by the Ghanaian Food and Drugs Authority in 2018, with long-acting insulin analogues currently listed in the Ghanaian EML [39,124]. However, long-acting insulin analogues are currently not included in the Ghanaian STGs for treating patients with diabetes nor currently reimbursed within the National Health Insurance Scheme (NHIS) due to their higher costs, severely limiting their prescribing within the public healthcare system [125,126]. Payment of service delivery among patients with diabetes in Ghana is both by insurance (national or private) and out-of-pocket; however over 90% of patients with diabetes are reported to be NHIS subscribers. The NHIS reimbursement list typically contains all medicines reimbursed by the government, and is based on the Ghanaian EML and the STGs. However, inclusion in the EML may not necessarily lead to inclusion in the NHIS as seen with the long-acting insulin analogues, similar to the current situation with the STGs.

As a result, there has been a sustained increased use of standard insulins including NPH or premixed insulins by physicians in the public hospitals in recent years in Ghana with very limited use of long-acting insulin analogues (Table 3). This is exacerbated by concerns with the catastrophic impact of illnesses such as diabetes outside of the NHIS and other schemes [127]. Such concerns may be reduced among children with diabetes in Ghana with Novo Nordisk seeking to offer insulin free to children during 2021 under is CDiC initiative, similar to the historic initiative in Cameroon [57].

Insulin type 2018 2019 2020 (Mid-Year)
Premixed insulins (30% insulin soluble/ 70% isophane) – 1000IU 197075 211700 163700
Other insulins, e.g. isophane – 10000IU 25000 35100 23000
Insulin glargine 3mls/ 100IU/ml (originator) 0 0 30
Total 222075 246800 186730
% insulin glargine 0% 0% 0.02%

Table 3: Insulin dispensing patterns in recent years in the cape coast teaching hospital, Ghana, in DDDs.

There has been a similar increase in the use of premixed 30/70 insulin within Keta Hospital in Ghana rising from 580 packs in 2015 to 802 in 2019 (38.3% increase), with this increase expected to continue (Table 4). Currently, there is no prescribing of long-acting insulin analogues within Keta Hospital due to price differences and affordability between the various insulins. This is likely to remain until there are appreciable price reductions for long-acting insulin analogues through for instance biosimilars.

    2015 2016 2017 2018 2019
Insulin Dosage Util Exp Util Exp Util Exp Util Exp Util Exp
Soluble (human) insulin 1000IU 100 100 110 100 120 150 135 255 145 50
Insulin premixed 30/70 1000IU 580 500 540 660 610 560 793 635 802 800

Table 4: Changes in utilisation and expenditure on different insulins in keta hospital, Ghana, in recent years.

Ghana’s National Medicines Policy document outlines data requirements for selecting essential medicines for national reimbursement. Medicines must be shown to be efficacious and cost-effective versus current standards reflecting the current demographic and economic situation within the country (Table 2). This enhances the need for more local research to be conducted to strengthen the case for potential funding of long-acting insulin analogues including their biosimilars and stronger communication of their benefits to policymakers [128]. This confirms the identified gap in knowledge regarding the overall cost-effectiveness of longacting insulin analogue biosimilars within Africa, which needs to be addressed going forward.

The availability of long-acting insulin analogues could potentially address issues of adherence to prescribed medicines, which remains a major challenge for patients with diabetes in Ghana [129]. However, similar to other African countries, there needs to be an appreciable lowering of the price of long-acting insulin glargine via lower-cost biosimilars to enhance their availability and usage within the public health system in Ghana [130]. Local production

Table 3: Insulin dispensing patterns in recent years in the cape coast teaching hospital, Ghana, in DDDs.

of biosimilars of long-acting insulin analogues, including pens and cartridges, may be one way forward to lower prices and enhance their future use [131].

Kenya: Ongoing concerns with affordability of medicines for diabetic patients, including co-morbidities, has resulted in very variable availability and use of long-acting insulin analogues in Kenya in recent years [7,50,52]. This includes the leading tertiary hospital in Kenya-Kenyatta National Hospital (KNH), a level six hospital, where there has been increasing use of long-acting insulin analogues in recent years despite falling availability of insulins within the hospital [52] (Table 5). Overall, total insulin use within KNH decreased from a total of 591747.5 DDDs in 2015 to 306717.5 in 2019 and 244137.5 between January and October 2020, with this falling use compensated by greater purchasing in local community pharmacies. However, whilst there has been growing use of longacting insulin analogues in recent years in KNH, this only rose to between 3.2% to 3.6% of total insulin use from 0.51% in 2015 (Table 5).

Insulin type 2015 2016 2017 2018 2019
Rapid acting 950 725 1200 2775 1257.5
Intermediate acting 16250 19025 19425 28062.5 33875
Premixed 571532.5 321050 221210 231690 260510
Glargine 3015 1260 3202.5 8680 11075
Total (DDDs) 591747.5 342060 245037.5 271207,5 306718
% long-acting insulin analogues 0.51% 0.37% 1.31% 3.20% 3.61%

Table 5: Total utilisation of insulins in KNH 2015 to 2019 (DDDs) [100].

This usage patterns for insulins in KNH Table 5, reflects current insulins listed within the 2019 Kenyan EML coupled with issues of affordability [99].

However, it is likely there will be limited or no use of long-acting insulin analogues, including potential biosimilars, outside of KNH with patients in Kenya struggling to fund even insulin Mixtard® Table 1, without access schemes [51]. This was seen in Embu County Referral hospital, which is a level 5 hospital located in Central Kenya, a region with high prevalence of diabetes mellitus in Kenya. Mixtard® was the principal insulin dispensed with usage rising from 2061 packs in 2015 (511,360 Ksh; US$4660) to 5627 packs in 2018 (1,800,640 Ksh; US$16410) before falling to 4742 packs in 2019 with similar utilisation patterns in 2020. There was no dispensing of any long-acting insulin analogue in this referral hospital in recent years.

Consequently, similar to Cameroon and Ghana, prices of longacting insulin analogues such as insulin glargine or detemir, including their biosimilars, will need to appreciably fall before there is any considerable use. This especially since when any prescribed medicine is not available or stocked in hospitals; patients necessarily need to purchase them directly from community pharmacies. This is a growing occurrence, with patients often needing to pay for these medicines out of pocket thereby making affordability a key consideration [100].

Namibia: There is universal access to care for patients in the public sector within Namibia, including free medicines, which can be accessed from primary health care to tertiary institutions [132]. Whilst a wide range of insulins, including soluble and long-acting insulin analogues, are currently available to the public via PHCs financed by the Government of the Republic of Namibia, there is currently limited use of long-acting insulin analogues in public sector hospitals in Namibia due to issues of affordability [7].

Long-acting insulin analogues (originator insulin glargine) is currently available in the two main State public hospitals in Windhoek (Capital city of Namibia). These include Katutura Intermediate Hospital (KIH) and Windhoek Central Hospital (WCH). However in KIH, typically only 1-2 pens of insulin glargine (originator) are dispensed per month compared to NPH and other similar insulins being dispensed to over 30 patients a day. In WCH, isophane is the most dispensed insulin (in approximately 70% of patients to improve control of HbA1c levels), with 50% of patients also being dispensed short-acting insulins. Biphasic insulins are also dispensed in WCH – greater when there are shortages of isophane, with little or no dispensing of insulin glargine. However, longacting insulin analogues are available and used in private hospitals in Namibia as the principal long-acting insulin. This is typically originator insulin glargine with currently no use of biosimilar insulin glargine.

Overall, prices of long-acting insulin analogues such as insulin glargine or detemir will need to fall considerably through biosimilars to enhance their use in the public sector in Namibia, similar to other African countries.

Nigeria: Short-acting or mealtime insulins as well as insulins including premixed and NPH insulin and long-acting insulin analogues, insulin glargine, are currently contained in the Nigerian EML. However, there are concerns with the affordability and availability of insulins including insulin glargine in Nigeria [7].

Among three hospitals in the Northern part of Nigeria, the total annual utilisation of insulin glargine originator was limited versus short and intermediate-acting insulins (Table 1). In 2019, utilisation of insulin glargine (originator) among these three hospitals ranged from 50 to 100 packs of 5x3ml 100IU/ml, with prices per pack ranging from N3600 (US$9.47) to N4300 ($11.42). There were similar utilisation patterns in the first half of 2020; however, prices rose from N4000 (US$10.53) to N4500 (US$11.84).

Among 11 community pharmacies surveyed in 2019 and 2020, the average number of packs of insulin glargine 100IU/ml dispensed ranged from 35 to 110 per year, with an average of 75 packs. Similar patterns were seen in the first half of 2020. Biosimilar Glaritus® accounted for only a small proportion of this at under 10%, with similar low rates of biosimilar dispensing in 2020. This may reflect concerns generally with the quality of non-originator medicines in Nigeria [133]. As well as limited price differences in reality between the originator and biosimilars, e.g., currently only a 4% difference between the biosimilar and the cheapest originator insulin glargine among the surveyed pharmacies.

Prices of long-acting insulin analogues through biosimilars will need to appreciably fall to enhance their use within public facilities in Nigeria given current high patient co-payment levels and concerns generally with the impact of diabetes on patients’ families. This is similar to other African countries.

Zimbabwe: Long-acting insulin analogues have been listed within the EML/STGs of Zimbabwe since 2015 (EDLIZ 7th and 8th editions) [98]. This includes both insulin glargine and insulin detemir. However, in view of their additional costs versus NPH and other insulins, and available resources, their availability within central provincial and district public hospitals in Zimbabwe is currently erratic and inconsistent. Long-acting insulin analogues including degludec were last purchased in 2018 and distributed up to the end of 2019/beginning of 2020.

Usage of long-acting insulin analogues is further limited in Zimbabwe by the economic burden of NCDs generally including diabetes on households [134,135]. Consequently, the most accessible insulins currently in Zimbabwe include short and intermediate acting insulins including premixed insulins Table 1, Prices of long-acting insulin analogues through biosimilars will have to appreciably fall in Zimbabwe to enhance their use, again similar to other African countries.

African countries where long-acting analogues are currently not funded or listed in the public healthcare system

Botswana: Short and intermediate-acting insulins as well as premixed insulins are currently available in the public healthcare system in Botswana [7]. These insulins are typically available in specialized diabetes clinics, with only a few insulins available in non-specialised clinics using special prescription forms (e.g., NovoMix® and NovoRapid®, i.e. insulin as part). Long-acting insulin detemir is registered in Botswana but currently unavailable in the public healthcare system. This is likely to be different in the private system. Insulin glargine (originator or biosimilar) is also currently unavailable in the public healthcare system in Botswana

However, it is envisaged that appreciably lowering the price of long-acting insulin glargine via lower-cost biosimilars towards the corresponding prices of NPH and other insulins will increase the availability and use of long-acting insulin analogues within the public health system in Botswana, again similar to other African countries.

Eswatini (formerly Swaziland): Currently, long-acting insulin analogues are not listed in the EML of the Kingdom of Eswatini. The only available insulins within the public healthcare system include insulins such as isophane and premixed insulins (30/70) all at 100units/ml [136]. In addition, whilst insulin protaphane is currently not listed in the Eswatini EML, it is stocked in some government hospitals and Army clinics to help improve patient care in view of its perceived longer action.

Long-acting insulin analogues such as insulin glargine are currently unavailable in the public hospitals in Eswatini; however, they are available in private hospitals. This illustrates issues of affordability with more expensive insulin formulations, including long-acting insulins analogues, as the Kingdom of Eswatini strives towards Universal Healthcare (UHC) in accordance with agreed sustainable development goals for NCDs [137-139].

As a result, there is currently limited prescribing of long-acting insulin analogues in the Kingdom with the current EML/STG being used to guide prescribing practices [140]. This is exacerbated by frequent stock-out of medicines within public facilities especially those for NCDs, with patients guided towards private pharmacies to purchase their medicines subject to high co-payments [140].

The current wholesale prices of insulin protaphane presenting as 5 × 3 ml cartridges is Rand 633.00 (US$42.80), with insulin glargine 100IU/ml 17% higher at Rand 727 (US$49.16) for a 5 × 3 ml cartridge (similar DDDs). This is encouraging with potential reductions in the price of insulin glargine through biosimilars towards isophane insulin, coupled with additional education of key Government personnel in Eswatini. As a result, potentially improving the chances of biosimilar insulin glargine being listed in the EML and funded within the public healthcare system in Eswatini in the future.

Malawi: There are concerns with the identification and management of patients with diabetes in Malawi, especially in rural settings where there is limited availability of standard insulins within health centres [141]. Similarly, standard insulins such as 10ml soluble insulin (100 IU/ml)) was only available among 25.0% of surveyed public hospitals and 36.4% of surveyed Christian Health Association of Malawi (CHAM) facilities in a recent paper [142]. As expected, there was higher availability of these insulins among private pharmacies [142].

Table 6, shows variable dispensing of different insulins in Queen Elizabeth Central Hospital in Malawi between 2015 and 2020, with Box 1 describing variations in the availability of different insulins in Malawi via the Central Stores.

Variable availability of different insulins among hospitals in Malawi

• Insulin soluble - no data available for 9-7-15 to 30-6-16 and 1-7-18 to 9-7-19.

• Insulin lente (intermediate acting insulin) - no data available for 1-7-16 to 1-11-16 and 1-7-18 to 1-7-19 and concerns generally with availability.

• Insulin biphasic - no data available for 1-1-18 to 1-7-19.

• Usage of premixed insulins properly starting from 2018 onwards with recordings from 2019 onwards (Table 6).

Insulin name 2015 2016 2017 2018 2019 2020 (Jan to June)
Soluble insulin injection (INSUGEN-R®, regular) 340 625 1140 830 852 570
Isophane insulin (INSUGEN-R®, NPH)) 5719 5090 7640 4360 4560 4850
Premixed (30% insulin soluble and 70% isophane insulin)         110 80

Table 6: Packs of insulin dispensed in the queen elizabeth central hospital, Malawi, 2015 to 2020.

However, electronic medical records are being introduced in hospitals in Malawi to improve the care of patients with diabetes, and we will be monitoring this progress [143].

There are currently no long-acting insulin analogues available in the public healthcare system in Malawi reflecting the lack of listing in the EML [144]. In addition, concerns with appreciably higher costs those other insulins including NPH and other similar insulins. It may again be that appreciably lower costs of long-acting insulin analogues via biosimilars can help enhance their listing and use in Malawi in the future.

South Africa: Increasing prevalence of diabetes in South Africa has resulted in the utilisation of insulin within the public healthcare system in South Africa rising to 3.19billion DDDs in 2019, an increase of 11.1% compared with 2018. Encouragingly, expenditure on insulins went down by 3.6%, suggestive of the additional savings that can be made through economies of scale.

Currently, long-acting insulin analogues are unavailable within the public healthcare system in South Africa due to concerns with their appreciably higher costs versus basal/NPH insulins and no perceived clinical advantage [96]. Having said this, the costs of long-acting insulin analogues are likely to come down in price with greater competition from greater availability of different biosimilars of long-acting insulin analogues (Table 7 for Public Hospitals and Table 1 for Private Hospitals). This will build on the current 28% price difference between 5 by 3ml cartridges of biosimilar insulin glargine versus insulin detemir and a 22.6% price difference between the originator (10 ml 100IU/ml) and biosimilar insulin glargine (5 by 3ml pen sets) on a DDD basis (Table 7). Having said this, the price of the disposable pens for biosimilar insulin glargine are still 2.8 times higher than those of intermediate acting insulins.

The ministerially appointed South African National Essential Medicines List Committee recently reviewed long-acting insulin analogues for use at the tertiary and quaternary level of care [96]. Consideration of therapeutic grouping of intermediate-acting and long-acting insulin analogues, coupled with respective pooled procurement/tendering, may potentially assist with access to longacting insulin analogues from primary to quaternary levels of care in the future in South Africa with more affordable prices. This builds on current procurement prices for biosimilar insulin glargine within the public healthcare system in South Africa (Table 7).

INSULIN TYPE TRADE NAME EML status * PRICE**
Short-acting (Fast-acting) (human) Actrapid® HM, 100IU/ml, disposable cartridge (5x3ml) EML R164.10 (US$11.11)
Intermediate-acting (human) Protaphane HM, 100IU/ml, disposable cartridge (5x3ml) EML R164.10 (US$11.11)
Premixed Actraphane® HM 30/70, 100 IU/ml, disposable cartridge (5x3ml) EML R164.10 (US$11.11)
Insulin glargine (Originator) Lantus® 100IU/ml, vial (1x10ml) NON-EML R534.57 (US$36.25)
Insulin glargine (biosimilar) Optisulin® 100IU/ml (manufactured by Sanofi), cartridges (5x3ml) NON-EML R460.40 (US$31.41)
Insulin detemir Levemir® 100IU/ml, disposable pen (5x3ml) NON-EML R639.20 (US$43.61)

Table 7: Current prices among public hospitals in South Africa.

However, since cost considerations are likely to remain a key issue in South Africa when appraising procurement of medicines within the public system given the desire to maintain universal healthcare whilst faced with growing pressure on resources, prices of longacting insulin analogue biosimilars will need to fall considerably if they are to be funded within the public healthcare system in South Africa [145].

Tanzania: Currently long-acting insulin analogues are not available with the Tanzanian EML/STGs due to issues of affordability and concerns [146]. The routine availability of appreciably lower costs human insulins such as NPH insulin will make it more challenging for long-acting insulin analogues, including their biosimilars, to become routinely available in the EML. This needs to be addressed before long-acting insulin analogues become routinely available in Tanzania.

Uganda: There are ongoing concerns with the management of patients with diabetes in Uganda, and similar to other African countries an appreciable number of patients are unable to afford prescription medicines especially insulins along with equipment to monitor their blood glucose levels [147,148]. Consequently, there is a continuing need for national strategies to promote improved access to affordable medicines and diagnostic tests for patients with diabetes mellitus and CVD to reduce associated morbidity and mortality in Uganda [148]. There are also ongoing concerns regarding routine screening for complications such as microvascular complications and CVD in Uganda [149].

In Uganda, long-acting insulin analogues, including insulin glargine, are currently not listed in the Ugandan EML, which is a concern given the high rates of hypoglycaemia currently seen.

This reflects issues of affordability in Uganda, which is a major issue [147]. Currently, prices for insulin glargine for patients within the healthcare system in Uganda vary between US$15 - $35/ pen depending on whether this is a biosimilar or originator, and whether at a hospital or community pharmacy. We have seen similar prices in other LMICs [44,92]. Typically, adolescents with diabetes require 2 pens/month, with overall costs considerably higher than US$8-10 for soluble insulin, NPH insulin at $9-10, with premixed insulin at $10-15 all at 1000 IU (i.e., 10 ml of 100 IU/ml) with each 10 ml vial lasting approximately 25–30 days.

Overall, it is believed that prices of biosimilar insulin glargine would need to fall appreciably for listing of long-acting insulin analogues in the National EML and more widely used. Addressing these challenges should though improve the care of patients with diabetes mellitus in Uganda and reduce the complications in patients with diabetes requiring insulin [150]. Improving caretaker involvement and other factors including a variety of insulin preparations available should help address key issues such as adherence to insulin therapy, further improving the care of patients with diabetes in Uganda and reducing associated morbidity and mortality [151].

Zambia: Similar to other African countries, there are concerns with the management of patients with diabetes mellitus in Zambia to reduce complications as well as address stock-outs of short, intermediate and longer-acting insulins common among public facilities [97,152]. Stock-outs among public facilities are a major challenge to patients in Zambia as this necessitates them having to either purchase their insulin from private pharmacies subject to 100% co-payment or through insurance schemes [97]. Having said this, there are concerns with the routine availability of short and intermediate-acting insulins within private pharmacies in Zambia, with prices typically higher than international reference prices, which also needs to be addressed [121].

To help with the availability of insulins within public healthcare facilities, the government of the Republic of Zambia has been routinely purchasing insulins listed in the Zambian EML. This includes protaphane as its longer acting insulin alongside both short and more intermediate-acting insulins. There has been no purchasing of long-acting insulin analogues including biosimilar insulin glargine as these are currently not listed in the Zambia EML due to issues of affordability and value [97,121]. We are also aware that in Zambia, there are initiatives in place for patients to receive free or subsidized insulins through the national health insurance scheme operationalised in 2020 to address issues of access, affordability and availability and we will be following this up in future research projects [7,153].

Usage of insulin protaphane within the University Teaching Hospitals in Lusaka has increased in recent years from 4130 vials in 2018, 9631 vials in 2019 and 3888 vials up to June 2020, with this growth rate likely to continue. Overall, it is believed that prices of long-acting insulin analogues, including biosimilar insulin glargine, would need to be close to those of insulin protaphane for insulin glargine to be prescribed and funded within the public healthcare system in Zambia. This is similar to a number of other African countries.

Discussion

We believe this is the first study to document current utilisation patterns of long-acting insulin analogues across Africa and the rationale for either no or limited use within the different public healthcare systems. The first step within African countries is to ensure that patients with T1DM and T2DM are treated well, which includes enhancing access to pertinent treatments [4,7]. In the case of patients with T2DM, which represent the vast majority of patients with diabetes in Africa, activities should include improving diagnosis as well as aggressive early management with appropriate oral medicines to prevent progression to diabetes requiring insulin for management [4]. It is likely that mobile technologies will be increasingly used across Africa to help improve the management of patients with diabetes mellitus and associated complications especially given some of the concerns with monitoring patients with NCDs arising from the recent COVID-19 pandemic [115,154]. Mobile technologies can be used to provide education to patients with diabetes to improve their self-care as well as monitor their status including their HbA1c levels, adherence levels to prescribed medicines, weight and lifestyle changes [154,155]. In addition, appointment reminders as lockdown pressures ease [156].

However, if patients require insulin for their management, we are seeing global sales of long-acting insulin analogues increasing with worldwide sales of long-acting insulin glargine potentially rising to US$9.26 billion by 2025, with, as mentioned, worldwide sales of long-acting insulin detemir at US$2.7 billion in 2015 and growing at 7.5% per year [157,76]. Utilisation of long-acting insulin analogues now exceeds that of human insulins among uppermiddle and high-income countries and we are also seeing the growing use of long-acting insulin analogues in countries such as Bangladesh as well as lower income Central and Eastern European countries [39,75,92,95,102]. This reflects their perceived role with reducing rates of hypoglycaemia versus standard insulins such as NPH insulins as well as improving patient convenience. There are though ongoing controversies surrounding the benefits of longacting insulin analogues as seen in the recent Cochrane Review by Hemmingsen et al. (2021) [77]. However, countered to some extent by the recent systematic review combined with a network analysis by Tricco et al. (2021) [78]. This is accentuated in Africa by the fact that compartive studies between NPH insulins and longacting insulin analogues have typically been undertaken in highincome countries with very different circumstances to patients with diabetes in LMICs including those in Africa.

There are also concerns across Africa with the appreciably higher price of long-acting insulin analogues versus NPH and other insulins, and issues of affordability even with NPH and other insulins [39]. This is reflected in the variable listing of long-acting insulin analogues on national EMLs across Africa (Table 2), building on the lack of listing in the current WHO EML [123]. Even if listed on national EMLs, there can be concerns with their funding due to current high prices as seen in Ghana where longacting insulin analogues are not currently listed in the NHIS or in their STGs despite listing in their EML. In addition, limited use in Cameroon, Kenya, Namibia, Nigeria and Zimbabwe despite longacting insulin analogues being listed in their EMLs. The high prices for long-acting insulin analogues are exacerbated by the fact that, as mentioned, the insulin market is dominated by 3 manufacturers who between them account for up to 96% of the global market by volume and up to 99% by value [41-44].

Based on our findings, coupled with ongoing activities in other countries especially other LMICs, we believe that a number of concurrent activities are needed to enhance the listing and funding of long-acting insulin analogues across Africa, including their biosimilars, to expand available choices. These include multiple activities to help obtain low cost biosimilar insulin glargine through for instance increasing competition as well as studies demonstrating the benefits of long-acting insulin analogues among African patients. Following this, educational activities to enhance their use especially if there are differences in pens and devices between different long-acting insulin analogue presentations [158]. Summarises a number of concurrent activities that are needed to enhance the availability of low cost biosimilar insulin glargine given the perceived low cost-of-goods versus for instance insulin detemir and affordability being a key issue across Africa [7,39,44,131]. As seen in South Africa and other African countries appreciably lowering procured prices for biosimilar insulin glargine will improve their chances for listing in national EMLs [96].

Potential activities to enhance the availability of low cost biosimilar insulin glargine within public healthcare systems across Africa

• Increased competition can potentially lower the prices of long-acting insulin analogue biosimilars such as biosimilar insulin glargine as seen with biosimilars in other situations [89,159]. This can potentially be achieved by:

By Governments/procurement agencies building on the WHO prequalification initiative to enhance imports of long-acting insulin analogue biosimilars from other LMICs including Bangladesh, China, India and Malaysia [44,46,92,107].

Governments/procurement agencies working with traditional insulin manufacturers and others to make long-acting insulin analogues available at lower prices, building on initiatives in Cameroon, Kenya and Nigeria, as well as Biocon’s ‘Mission 10 cents’ initiative for recombinant human insulin (rh-insulin) [47- 49,51,57,160,59]. This is potentially challenging given the current monopoly among the three principal insulin manufacturers currently accounting for up to 99% of the value of the global insulin market however, potentially facilitated by purchasing consortia building on initiatives across Europe [44,161,162].

Governments (especially across regions) seeking to produce biosimilar insulin glargine within Africa. Biocon already supplies insulin analogues, including biosimilar insulin glargine, to a number of African countries, and was instrumental in developing appreciable manufacturing capabilities in Malaysia in addition to providing low cost recombinant human insulins in Tanzania [107,163,59]. The progression of consortia such as the East African Community consortia, which advocated increased local production of essential equipment and medicines to address future shortages arising from the COVID-19 pandemic as well as the South African Development Community (SADC), provide a forum for such discussions [115,164,165]. Such discussions can build on ongoing existing country initiatives regarding a ‘GMP road Map’ for Africa, which is now being progressed in a number of African countries including Ghana [116,166,167].

• Similar to this, key government personnel within groups such as West African Groups, East African Community consortia and the South African Development Community (SADC) can unite to push for low prices for biosimilar insulin glargine [116,164,165], building on current successes in South Africa with their procurement practices for insulin (Section 3.2.3). This also builds on current initiatives with purchasing consortia across Europe [161,162].

• Governments/Ministries of Health should seek to only list biosimilars (of proven quality) on EMLs, e.g. biosimilar insulin glargine 100 IU/ml on national EMLs/health insurance lists, and not originators to further enhance competition among biosimilar manufacturers. Ideally, biosimilar long-acting insulin analogues should be no more than 30% to 50% more expensive than NPH and other insulins on a daily basis, especially with patients in a number of African countries struggling to fund standard insulins

• Concurrent with this:

WHO African and others could seek to expand the remit of the Medicines Patent Pool as well as use of the flexibilities enshrined in the WHO TRIPS agreement to increase access and availability of insulin glargine including biosimilars at affordable prices to enhance their listing and affordability.

Pan-African consortia, with the help of WHO Africa, should also seek to ensure where possible consistency in prices for biosimilar insulin glargine across Africa to reduce issues of parallel exportation and other concerns.

Ministries of Health and/or physicians’ groups should seek to enhance local knowledge of the potential patient benefits with long-acting insulin analogues through clinical trials and real-world evidence studies.

Ministries of Health/Physician Groups should ensure consistency between country EMLs and STGs given current concerns in Ghana.

Ministries of Health and other key stakeholder groups should work together to ensure the routine availability of biosimilar long-acting insulin analogues among all public health facilities especially hospitals/clinics to enhance competition (and also avoid unnecessary co-pays if patients have to pay for the insulin themselves in community pharmacies).

Governments should re-look at key issues such as cumulative markups for medicines within a country, especially for high priority diseases such as diabetes, where there are high patient co-payments as mark-ups have ranged up to 565.8% for insulins among LMICs [112].

Once low cost biosimilar long-acting insulin analogues are available and funded within countries, including listing on country EMLs, there are a number of educational and other initiatives that can be undertaken within African countries to enhance their use. These are summarised in below.

Potential activities to enhance the utilisation of biosimilar insulin glargine within public healthcare systems across Africa once routinely available

• Key personnel within Ministries of Health and Physician/ Pharmacy Groups should work together to collate ongoing clinical evidence among LMICs to support the continued listing of long-acting insulin analogues within EMLs/ funding within public healthcare systems

• Key physician/pharmacy groups should seek to educate all key stakeholder groups regarding similar effectiveness and safety between originator and biosimilar long-acting insulin analogues as more data becomes available across LMICs including Africa to avoid/reduce any negative nocebo effects [168].

• Physicians and pharmacists (as well as nurse practitioners in primary healthcare clinics) should work with patients to ensure they are familiar with the different pens/devices if this is the case between different long-acting insulin analogues including originators and biosimilars; however, reduced with national procurement practices

• In addition, key Ministry of Health personnel along with physicians and pharmacists should work with patient organisations where pertinent to reduce any misinformation about biosimilars for long-acting insulin analogues to facilitate greater use especially where resources/co-payments are an issue. This includes where pertinent warning patients that devices may be different between originators and biosimilars

• Where pertinent, Ministry of Health personnel could potentially introduce target prescribing goals (quality indicators) for starting suitable patients on 100 IU/ml biosimilar insulin glargine where possible when prescribing a long-acting insulin analogue similar to initiatives among a number of European countries for biosimilars [90,169].

• Physician and Pharmacy Groups should seek to monitor HbA1c and hypoglycaemia rates in patients prescribed long-acting insulin analogues to see if reduced rates of hypoglycaemia/improved control are seen in practice, and subsequently broadcast their findings to enhance future use building on published studies. Concurrent with this, these groups work with Governments and others to seek ways to enhance the routine availability of strips to improve home monitoring of blood glucose levels given current concerns

We are aware of a number of limitations with this study. These include the fact that we were not able to collect national data on pricing and utilisation of the different insulins outside of South Africa. In addition, we only collected pharmacy data from Nigeria. However, we were able to collect pricing and expenditure data from a number of sources in different countries. In addition, we did not formally test potential prices for long-acting insulin analogue biosimilars (insulin glargine) to be considered for inclusion in national EMLs where this is currently an issue as well as for increased funding and usage. Despite these limitations, we believe our findings are robust providing direction for the future.

Conclusion

There are continuing concerns with the growing prevalence rates of diabetes mellitus across Africa including patients requiring insulin and the implications for future morbidity and mortality. Hypoglycaemia is an increasing concern enhancing complication rates, and long-acting insulin analogues can potentially address this. However, the considerably higher costs of these analogues versus NPH and other insulins has appreciably limited their utilisation and funding in practice across Africa including listing on national EMLs. Biosimlar long-acting insulin analogues can potentially enhance future listing on EMLs and funding of these analogues; however, prices will need to appreciably fall to achieve this alongside increasing evidence of their benefits among patients in Africa.

References

  1. Liu J, Ren ZH, Qiang H, Wu J, Shen M, Zhang L, et al. Trends in the incidence of diabetes mellitus: results from the global burden of disease study 2017 and implications for diabetes mellitus prevention. BMC public health. 2020;20(1):1-2.
  2. Kibirige D, Lumu W, Jones AG, Smeeth L, Hattersley AT, Nyirenda MJ. Understanding the manifestation of diabetes in sub Saharan Africa to inform therapeutic approaches and preventive strategies: A narrative review. Clin diabetes endocrinol. 2019;5(1):1-8
  3. Chan JC, Lim LL, Wareham NJ, Shaw JE, Orchard TJ, Zhang P, et al. The lancet commission on diabetes: Using data to transform diabetes care and patient lives. The Lancet. 2020;396(10267):2019-2082
  4. Godman B, Basu D, Pillay Y, Mwita JC, Rwegerera GM, Anand Paramadhas BD, et al. Review of ongoing activities and challenges to improve the care of patients with type 2 diabetes across Africa and the implications for the future. Frontiers pharmacol. 2020;11:108
  5. Hamid S, Groot W, Pavlova M. Trends in cardiovascular diseases and associated risks in sub-saharan Africa: A review of the evidence for Ghana, Nigeria, South Africa, Sudan and Tanzania. The aging male. 2019;22(3):169-176.
  6. Godman B, Basu D, Pillay Y, Almeida P, Mwita JC, Rwegerera GM, et al. Ongoing and planned activities to improve the management of patients with type 1 diabetes across Africa; implications for the future. Hospital practice. 2020;48(2):51-67
  7. Dessie G, Mulugeta H, Amare D, Negesse A, Wagnew F, Getaneh T, et al. A systematic analysis on prevalence and sub-regional distribution of undiagnosed diabetes mellitus among adults in African countries. J diabetes metabolic disord. 2020;19(2):1931-1941
  8. Asamoah-Boaheng M, Sarfo-Kantanka O, Tuffour AB, Eghan B, Mbanya JC. Prevalence and risk factors for diabetes mellitus among adults in Ghana: A systematic review and meta-analysis. Int health. 2019;11(2):83-92
  9. Prevalence-of-obesity%2C-hypertension%2C-and-diabetes%2C-Price-Crampin/42793f531c8c2b12b94e102900fbb236fd15e6d1' target='_blank'>Price AJ, Crampin AC, Amberbir A, Kayuni-Chihana N, Musicha C, Tafatatha T, et al. Prevalence of obesity, hypertension, and diabetes, and cascade of care in sub-saharan Africa: A cross-sectional, population-based study in rural and urban Malawi. Lancet Diabetes endocrinol. 2018;6(3):208-222.
  10. Amberbir A, Lin SH, Berman J, Muula A, Jacoby D, Wroe E, et al. Systematic review of hypertension and diabetes burden, risk factors, and interventions for prevention and control in Malawi: The NCD BRITE consortium. Global heart. 2019;14(2):109-118.
  11. Tino S, Wekesa C, Kamacooko O, Makhoba A, Mwebaze R, Bengo S, et al. Predictors of loss to follow up among patients with type 2 diabetes mellitus attending a private not for profit urban diabetes clinic in Uganda: A descriptive retrospective study. BMC Health Serv Res. 2019;19(1):1-9
  12. Mohan V, Shah SN, Joshi SR, Seshiah V, Sahay BK, Banerjee S, et al. Current status of management, control, complications and psychosocial aspects of patients with diabetes in India: Results from the DiabCare India 2011 Study. Indian J Endocrinol Metab. 2014;18(3):370
  13. Venkataraman AP, Kamath L, Shankar S. Knowledge, attitude and practice of insulin use of diabetic patients in India. Med care. 2020;5:6
  14. Elliot J, Besançon S, Sachs J. Almost 100 years after it was discovered; let’s make access to insulin a reality in Africa! 2016
  15. Mbanya JC, Aschner P, Chan JC, Gagliardino JJ, Saji J. Self-monitoring of blood glucose (SMBG) and glycaemic control in Cameroon: Results of the international diabetes management practices study (IDMPS). Diabetes research clin pract. 2017;126:198-201.
  16. Bommer C, Sagalova V, Heesemann E, Manne-Goehler J, Atun R, Bärnighausen T, et al. Global economic burden of diabetes in adults: Projections from 2015 to 2030. Diabetes care. 2018;41(5):963-970.
  17. Bahendeka SK. Diabetes in sub-saharan Africa: Let us not forget type 1. Lancet Diabetes Endocrinol. 2017;5(8):575-577
  18. Mapa-Tassou C, Katte JC, Maadjhou CM, Mbanya JC. Economic impact of diabetes in Africa. Curr Diab Rep. 2019;19(2):5
  19. Bigna JJ, Noubiap JJ. The rising burden of non-communicable diseases in sub-saharan Africa. Lancet Glob Health. 2019;7(10):e1295-e1296.
  20. Gouda HN, Charlson F, Sorsdahl K, Ahmadzada S, Ferrari AJ, Erskine H, et al. Burden of non-communicable diseases in sub-saharan Africa, 1990-2017: Results from the global burden of disease study 2017. The Lancet Glob Health. 2019; 7(10):e1375-1387.
  21. Atun R, Davies JI, Gale EA, Bärnighausen T, Beran D, Kengne AP, et al. Diabetes in sub-saharan Africa: From clinical care to health policy. Lancet Diabetes Endocrinol. 2017; 5(8):622-667.
  22. Mudie K, Jin MM, Tan LK, Addo J, Dos-Santos-Silva I, Quint J, et al. Non-communicable diseases in sub-saharan Africa: A scoping review of large cohort studies. J Glob Health. 2019; 9(2): 020409.
  23. Mutowo MP, Lorgelly PK, Laxy M, Renzaho A, Mangwiro JC, Owen AJ. The hospitalization costs of diabetes and hypertension complications in Zimbabwe: Estimations and correlations. J Diabetes Res. 2016;2016:9754230.
  24. Amon SK, Aikins MK. Economic burden of type 2 diabetes mellitus complications among patients in the eastern region of Ghana: A descriptive cross-sectional cost-of-illness study. Diabetes Manag. 2017; 7(5):367-376.
  25. Mutyambizi C, Pavlova M, Hongoro C, Groot W. Inequalities and factors associated with adherence to diabetes self-care practices amongst patients at two public hospitals in Gauteng, South Africa. BMC Endocr Disord. 2020;20(1):15.
  26. Pirie FJ, Jairam V, Paruk IM, Connolly C, Motala AA. High frequency of hypoglycaemia in patients with type 1 diabetes mellitus attending a tertiary diabetes clinic in Durban, South Africa. Diabetes Res Clin Pract. 2019;155:107783.
  27. James S, Sewpaul R, Reddy P, Madela S, Madela S. Early detection, care and control of hypertension and diabetes in South Africa: A community-based approach. Afr J Prim Health Care FAM Med. 2020; 12(1):1-9.
  28. Pastakia SD, Pekny CR, Manyara SM, Fischer L. Diabetes in sub-saharan Africa–from policy to practice to progress: Targeting the existing gaps for future care for diabetes. Diabetes Metab Syndr Obes. 2017;10:247.
  29. Tusa BS, Weldesenbet AB, Gemada AT, Merga BT, Regassa LD. Heath related quality of life and associated factors among diabetes patients in sub-saharan countries: A systemic review and meta-analysis. Health Qual Life Outcomes. 2021; 19(1):1-3.
  30. Rwegerera GM, Moshomo T, Gaenamong M, Oyewo TA, Gollakota S, Rivera YP, et al. Health-related quality of life and associated factors among patients with diabetes mellitus in Botswana. Alexandria J Med. 2018; 54(2):111-118.
  31. Ellapen TJ, Barnard M, Strydom GL, Masime KM, Paul Y. A comparison between selected non communicable disease mortality rates between 2010 and 2016 among selected southern African countries. Int Q Community Health Educ. 2021; 41(2):119-123.
  32. Asmelash D, Asmelash Y. The burden of undiagnosed diabetes mellitus in adult African population: A systematic review and meta-analysis. J Diabetes Res. 2019; 2019.
  33. Manne-Goehler J, Geldsetzer P, Agoudavi K, Andall-Brereton G, Aryal KK, Bicaba BW, et al. Health    system performance for people with diabetes in 28 low- and middle-income countries: A cross-sectional study of nationally representative surveys. PLoS Med. 2019; 16(3):e1002751.
  34. Djonou C, Tankeu AT, Dehayem MY, Tcheutchoua DN, Mbanya JC, Sobngwi E. Glycemic control and correlates in a group of sub saharan type 1 diabetes adolescents. BMC Res Notes. 2019;12(1):1-5.
  35. Babar ZU, Ramzan S, El-Dahiyat F, Tachmazidis I, Adebisi A, Hasan SS. The availability, pricing, and affordability of essential diabetes medicines in 17 low-, middle-, and high-income countries. Front Pharmacol. 2019;10:1375.
  36. Chang H, Hawley NL, Kalyesubula R, Siddharthan T, Checkley W, Knauf F, et al. Challenges to hypertension and diabetes management in rural Uganda: A qualitative study with patients, village health team members, and health care professionals. Int J Equity Health. 2019; 18(1):38.
  37. Ewen M, Joosse HJ, Beran D, Laing R. Insulin prices, availability and affordability in 13 low-income and middle-income countries. BMJ global health. 2019; 4(3):e001410.
  38. Wirtz VJ, Turpin K, Laing RO, Mukiira CK, Rockers PC. Access to medicines for asthma, diabetes and hypertension in eight counties of Kenya. Trop Med Int Health. 2018;23(8):879-885.
  39. WHO. Changing the game to improve availability and affordability of quality-assured insulin and associated devices. 2020.
  40.  Beran D, Laing RO, Kaplan W, Knox R, Sharma A, Wirtz VJ, et al. A perspective on global access to insulin: A descriptive study of the market, trade flows and prices. Diabet. Med. 2019;36(6):726-733.
  41. Beran D, Ewen M, Laing R. Access to insulin: Current challenges and constraints. Amsterdam: Health Action International. 2015.
  42. Beran D, Lazo-Porras M, Mba CM, Mbanya JC. A global perspective on the issue of access to insulin. Diabetologia. 2021; 64(5):954-962.
  43. Beran D, Hirsch IB, Yudkin JS. Why are we failing to address the issue of access to insulin? A national and global perspective. Diabetes Care. 2018; 41(6):1125-1131.
  44. WHO launches first-ever insulin prequalification programme to expand access to life-saving treatment for diabetes. WHO.2019.
  45. Lontchi-Yimagou E, Mapa-Tassou C, Dehayem MY, Essi MJ, Saji J, Takogue R, et al. The effect of free diabetes care on metabolic control and on health-related quality of life among youths with type 1 diabetes in cameroon. BMJ Open Diabetes Res Care. 2017; 5(1):e000397.
  46. Dehayem MY, Takogue R, Choukem SP, Donfack OT, Katte JC, Sap S, et al. Impact of a pioneer diabetes camp experience on glycemic control among children and adolescents living with type 1 diabetes in sub-saharan Africa. BMC Endocr Disord. 2016; 16(1):1-6.
  47. Schäfermann S, Neci R, Ndze EN, Nyaah F, Pondo VB, Heide L. Availability, prices and affordability of selected antibiotics and medicines against non-communicable diseases in western cameroon and northeast DR Congo. Plos one. 2020;15(1):e0227515.
  48. Mbui JM, Oluka MN, Guantai EM, Sinei KA, Achieng L, Baker A, et al. Prescription patterns and adequacy of blood pressure control among adult hypertensive patients in Kenya; findings and implications. Expert Rev Clin Pharmacol. 2017; 10(11):1263-1271.
  49. Shannon GD, Haghparast-Bidgoli H, Chelagat W, Kibachio J, Skordis-Worrall J. Innovating to increase access to diabetes care in Kenya: an evaluation of Novo Nordisk’s base of the pyramid project. Glob. Health Action. 2019; 12(1):1605704.
  50. Oyando R, Njoroge M, Nguhiu P, Sigilai A, Kirui F, Mbui J, et al. Patient costs of diabetes mellitus care in public health care facilities in Kenya. Int J Health Plann Manage. 2020; 35(1):290-308.
  51. Fadare JO, Enwere OO, Adeoti AO, Desalu OO, Godman B. Knowledge and attitude of physicians towards the cost of commonly prescribed medicines: A case study in three Nigerian healthcare facilities. Value Health Reg Issues. 2020;22:68-74.
  52. Aregbeshola BS, Khan SM. Out-of-pocket payments, catastrophic health expenditure and poverty among households in Nigeria 2010. J Health Policy Manag. 2018; 7(9):798-806.n
  53.  Fadare J, Olamoyegun M, Gbadegesin BA. Medication adherence and direct treatment cost among diabetes patients attending a tertiary healthcare facility in ogbomosho, Nigeria. Malawi Med J. 2015; 27(2):65-70.
  54. Mutyambizi C, Pavlova M, Chola L, Hongoro C, Groot W. Cost of diabetes mellitus in Africa: A systematic review of existing literature. Glob Health. 2018;14(1):1-3.
  55. Times P. Diabetes: Novo nordisk to offer free insulin to children in Nigeria, Ghana. 2020.
  56. Peck R, Mghamba J, Vanobberghen F, Kavishe B, Rugarabamu V, Smeeth L, et al. Preparedness of Tanzanian health facilities for outpatient primary care of hypertension and diabetes: A cross-sectional survey. Lancet Glob Health. 2014; 2(5):e285-e292.    
  57. Moosa A, Bezuidenhout S, Meyer JC, Godman B. Knowledge regarding medicines management of type 2 diabetes amongst patients attending a community health centre in South Africa. J Pharm Health Serv Res. 2019;10(1):13-28
  58. Habte BM, Kebede T, Fenta TG, Boon H. Barriers and facilitators to adherence to anti-diabetic medications: Ethiopian patients' perspectives. Afr J Prim Health Care Fam Med. 2017;9(1):1-9.
  59. Afaya RA, Bam V, Azongo TB, Afaya A, Kusi-Amponsah A, Ajusiyine JM, et al. Medication adherence and self-care behaviours among patients with type 2 diabetes mellitus in Ghana. PloS one. 2020;15(8):e0237710.
  60. Waari G, Mutai J, Gikunju J. Medication adherence and factors associated with poor adherence among type 2 diabetes mellitus patients on follow-up at kenyatta national hospital, Kenya. Pan Afr Med J. 2018; 29(1):1-5.
  61. Basu S, Wagner RG, Sewpaul R, Reddy P, Davies J. Implications of scaling up cardiovascular disease treatment in South Africa: A microsimulation and cost-effectiveness analysis. The Lancet Global health. 2019; 7(2):e270-e280.
  62. Kahsay H, Fantahun B, Nedi T, Demoz GT. Evaluation of hypoglycemia and associated factors among patients with type 1 diabetes on follow-up care at st. paul's hospital millennium medical college, addis Ababa, Ethiopia. J Diabetes Res. 2019;2019:9037374.
  63. Tiruneh GG, Abebe N, Dessie G. Self-reported hypoglycemia in adult diabetic patients in east gojjam, Northwest Ethiopia: Institution based cross-sectional study. BMC Endocr Disord. 2019;19(1):1-9.
  64. Standl E, Owen DR. New long-acting basal insulins: does benefit outweigh cost? Diabetes Care. 2016;Suppl 2:S172-179.
  65. Laranjeira FO, Andrade DKRC, Figueiredo A, Silva EN, Pereira MG. Long-acting insulin analogues for type 1 diabetes: An overview of systematic reviews and meta-analysis of randomized controlled trials. Plos one. 2018; 13(4):e0194801.
  66. Rys P, Wojciechowski P, Rogoz-Sitek A, Niesyczyński G, Lis J, Syta A, et al. Systematic review and meta-analysis of randomized clinical trials comparing efficacy and safety outcomes of insulin glargine with NPH insulin, premixed insulin preparations or with insulin detemir in type 2 diabetes mellitus. Acta diabetologica. 2015;52(4):649-662.
  67. Bjergaard PU, Kristensen PL, Nielsen BH, Nørgaard K, Perrild H, Christiansen JS, et al. Effect of insulin analogues on risk of severe hypoglycaemia in patients with type 1 diabetes prone to recurrent severe hypoglycaemia (Hypo Ana trial): A prospective, randomised, open-label, blinded-endpoint crossover trial. The lancet Diabetes endocrinol. 2014; 2(7):553-561.
  68. Semlitsch T, Engler J, Siebenhofer A, Jeitler K, Berghold A, Horvath K. (Ultra-)long-acting insulin analogues versus NPH insulin (human isophane insulin) for adults with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2020;11:Cd005613.
  69. Alemayehu B, Speiser J, Bloudek L, Sarnes E. Costs associated with long-acting insulin analogues in patients with diabetes. Am J Manag Care. 2018;24(8):Sp265-Sp272.
  70. Setty GS, Crasto W, Jarvis J, Khunti K, Davies MJ. New insulins and newer insulin regimens: A review of their role in improving glycaemic control in patients with diabetes. Postgrad Med J. 2016;92(1085):152-164.
  71. Berard L, Cameron B, Woo V, Stewart J. Replacing insulin glargine with neutral protamine hagedorn (NPH) insulin in a subpopulation of study subjects in the Action to control cardiovascular risk in diabetes (ACCORD): Effects on blood glucose levels, hypoglycemia and patient satisfaction. Can J Diabetes. 2015;39(4):296-301.
  72. Beran D, Ewen M, Laing R. Constraints and challenges in access to insulin: A global perspective. Lancet Diabets Endocrinol. 2016;4(3):275-285.
  73. Hemmingsen B, Metzendorf MI, Richter B. (Ultra-) long-acting insulin analogues for people with type 1 diabetes mellitus. Cochrane Database Syst Rev. 2021;3:Cd013498.
  74. Tricco AC, Ashoor HM, Antony J, Bouck Z, Rodrigues M, Pham B, et al. Comparative efficacy and safety of ultra-long-acting, long-acting, intermediate-acting, and biosimilar insulins for type 1 diabetes mellitus: A systematic review and network meta-analysis. J Gen Intern Med. 2021;19:1-3
  75. Davidson MB. Insulin analogs--is there a compelling case to use them? No! Diabetes Care. 2014;37(6):1771-1774
  76. Souza CAL, Acurcio DAF, Junior GAA, Nascimento RMDRC, Godman B, Diniz LM. Insulin glargine in a Brazilian state: Should the government disinvest? An assessment based on a systematic review. Appl Health Econ Health Policy. 2014;12(1):19-32.
  77. Almeida P, Silva TBC, De Assis Acurcio F, Guerra Junior AA, Araujo VE, Diniz LM, et al. Quality of life of patients with type 1 diabetes mellitus using insulin analog glargine compared with nph insulin: A systematic review and policy implications. Patient. 2018;11(4):377-389.
  78. Laranjeira FO, Silva EN, Pereira MG. Budget impact of long-acting insulin analogues: The case in Brazil. PloS One. 2016;11(12):e0167039.
  79. Ewen M, Zweekhorst M, Regeer B, Laing R. Baseline assessment of WHO's target for both availability and affordability of essential medicines to treat non-communicable diseases. PloS One. 2017; 12(2):e0171284.
  80. Lee TY, Kuo S, Yang CY, Ou HT. Cost-effectiveness of long-acting insulin analogues vs intermediate/long-acting human insulin for type 1 diabetes: A population-based cohort followed over 10 years. Br J Clin Pharmacol. 2020;86(5):852-860.
  81. Gordon J, Evans M, McEwan P, Bain S, Vora J. Evaluation of insulin use and value for money in type 2 diabetes in the United kingdom. Diabetes Ther. 2013;4(1):51-66.
  82. Shafie AA, Ng CH. Cost-effectiveness of insulin glargine and insulin detemir in the basal regimen for naïve insulin patients with type 2 Diabetes Mellitus (T2DM) in Malaysia. Clinicoecon Outcomes Res. 2020;12:333-343.
  83. Tricco AC, Ashoor HM, Antony J, Beyene J, Veroniki AA, Isaranuwatchai W, et al. Safety, effectiveness, and cost effectiveness of long acting versus intermediate acting insulin for patients with type 1 diabetes: Systematic review and network meta-analysis. BMJ. 2014;349:g5459.
  84. Tunis SL, Minshall ME, Conner C, McCormick JI, Kapor J, Yale JF, et al. Cost-effectiveness of insulin detemir compared to NPH insulin for type 1 and type 2 diabetes mellitus in the Canadian payer setting: Modeling analysis. Curr Med Res Opin. 2009;25(5):1273-1284.
  85. Jensen TB, Kim SC, Jimenez-Solem E, Bartels D, Christensen HR, Andersen JT. Shift from adalimumab originator to biosimilars in Denmark. JAMA Intern Med. 2020;180(6):902-903.
  86. Godman B, Fadare J, Kwon HY, Dias CZ, Kurdi A, Dias Godói IP, et al. Evidence-based public policy making for medicines across countries: Findings and implications for the future. J Comp Eff Res. 2021; 10(12):1019-1052.
  87. Matusewicz W, Godman B, Pedersen HB, Furst J, Gulbinovic J, Mack A, et al. Improving the managed introduction of new medicines: Sharing experiences to aid authorities across Europe. Expert Rev Pharmacoecon Outcomes Res. 2015; 15(5):755-758.
  88. Haque M, Islam S, Kamal ZM, Akter F, Jahan I, Rahim MSA, et al. Ongoing efforts to improve the management of patients with diabetes in Bangladesh and the implications. Hosp Pract. 2021;1-7.
  89. World Health Organization-Model List of Essential Medicines. 21st List 2019.
  90. Cefalu WT, Dawes DE, Gavlak G, Goldman D, Herman WH, Van Nuys K, et al. Insulin access and affordability working group: Conclusions and recommendations. Diabetes Care. 2018; 41(6):1299-1311.
  91. Godman B, Haque M, Leong T, Allocati E, Kumar S, Islam S, et al. The current situation regarding long-acting insulin analogues including biosimilars among African, Asian, European, and South American countries; findings and implications for the future. Front Public Health. 2021;9:671961.
  92. National Essential Medicines List Committee (NEMLC)-Tertiary and quaternary level essential medicines list Reviewed Items. Department of Health Republic of South Africa. 2020.
  93. Kalungia CA, Mwale M, Sondashi IS, Mweetwa B, Yassa P, Kadimba G. Availability of essential antihypertensive and antidiabetic medicines in public health facilities in Lusaka district, Zambia. Med J Zambia. 2017;44(3):140-148.
  94. Ministry of health republic of Kenya. Kenya Essential Medicines List. 2019.
  95. Opanga S, Njeri LW, Kimonge D, Godman B, Oluka M. Assessing utilisation and expenditure on long-acting insulin analogues in Kenya; findings and implications for the future. Sch Acad J Pharm. 2021;10(4): 63-70.
  96. Greener M. Why isn’t the NHS making the most of biosimilar insulin? Medicine. 2019; 30(8):21-24.
  97. Tubic B, Marković-Peković V, Jungić S, Allocati E, Godman B. Availability and accessibility of monoclonal antibodies in Bosnia and Herzegovina: Findings and implications. Medicine. 2021;5:1-7.
  98. Haque M, Islam S, Abubakar AR, Sani IH, Opanga S, Kamal ZM, et al. Utilization and expenditure on long-acting insulin analogs among selected middle-income countries with high patient co-payment levels: findings and implications for the future. J Appl Pharm Sci. 2021; 11(07):172-182.
  99. Moon JC, Godman B, Petzold M, Alvarez-Madrazo S, Bennett K, Bishop I, et al. Different initiatives across Europe to enhance losartan utilization post generics: Impact and implications. Front Pharmacol. 2014; 5:219.
  100. Godman B, Petzold M, Bennett K, Bennie M, Bucsics A, Finlayson AE, et al. Can authorities appreciably enhance the prescribing of oral generic risperidone to conserve resources? Findings from across Europe and their implications. BMC Medicine. 2014;12:98.
  101. Godman B, Wettermark B, van Woerkom M, Fraeyman J, Alvarez-Madrazo S, Berg C, et al. Multiple policies to enhance prescribing efficiency for established medicines in Europe with a particular focus on demand-side measures: Findings and future implications. Front Pharmacol. 2014;5:106.
  102. Godman B, Haque M, Kumar S, Islam S, Charan J, Akter F, et al. Current utilization patterns for long-acting insulin analogues including biosimilars among selected Asian countries and the implications for the future. Curr Med Res Opin. 2021:1-17.
  103. Leporowski A, Godman B, Kurdi A, MacBride-Stewart S, Ryan M, Hurding S, et al. Ongoing activities to optimize the quality and efficiency of lipid-lowering agents in the scottish national health service: influence and implications. Expert Rev Pharmacoeconomics Outcomes Res. 2018;18(6):655-66.
  104. WHO. WHO collaborating centre for drug statistics methodology. ATC/ DDD Index. 2021.
  105. Sefah I, Ogunleye O, Essah D, Opanga S, Rizvi N, Wamaitha A, et al. Rapid assessment of the potential paucity and price increases for suggested medicines and protection equipment for COVID-19 across developing countries with a particular focus on Africa and the implications. Front Pharmacol. 2021;11(2055).
  106. Opanga SA, Rizvi N, Wamaitha A, Sefah IA, Godman B. Availability of medicines in community pharmacy to manage patients with COVID-19 in Kenya; pilot study and implications. Sch Acad J Pharm. 2021;10(3):36-42.
  107. Ball D, Ewen M, Laing R, Beran D. Insulin price components: case studies in six low/middle-income countries. BMJ Global Health. 2019; 4(5):e001705.
  108. Cheng MM. Is the drugstore safe? Counterfeit diabetes products on the shelves. J Diabetes Sci Technol. 2009; 3(6):1516-1520.
  109. Ogunleye OO, Basu D, Mueller D, Sneddon J, Seaton RA, Yinka-Ogunleye AF, et al. Response to the novel corona virus (COVID-19) Pandemic Across Africa: Successes, challenges, and implications for the future. Front Pharmacol. 2020;11(1205).
  110. Ekeigwe AA. Drug manufacturing and access to medicines: The West African story-a literature review of challenges and proposed remediation. AAPS Open. 2019;5:3.
  111. Godman B, Haque M, Islam S, Iqbal S, Urmi UL, Kamal ZM, et al. Rapid assessment of price instability and paucity of medicines and protection for COVID-19 across Asia: Findings and public health implications for the future. Front Public Health. 2020; 8(744).
  112. Godman B, McCabe H, Leong TD. Fixed dose drug combinations - are they pharmacoeconomically sound? Findings and implications especially for lower- and middle-income countries. Expert Rev Pharmacoeconomics Outcomes Res. 2020; 20(1):1-26.
  113. Godman B, Haque M, McKimm J, Abu Bakar M, Sneddon J, Wale J, et al. Ongoing strategies to improve the management of upper respiratory tract infections and reduce inappropriate antibiotic use particularly among lower and middle-income countries: Findings and implications for the future. Curr Med Res Opin. 2020; 36(2):301-27.
  114. Kaiser AH, Hehman L, Forsberg BC, Simangolwa WM, Sundewall J. Availability, prices and affordability of essential medicines for treatment of diabetes and hypertension in private pharmacies in Zambia. Plos One. 2019; 14(12):e0226169.
  115. Guney Z. Insulin and its analogues-what are they for? TDM. 2019:2(1-2).
  116. World Health Organization model list of essential medicines. WHO. 2019.
  117. Ghana National Drugs Programme (GNDP) - essential medicines list. Ministry of Health Republic of Ghana. 2017.
  118. Ghana standard treatment guidelines. Ministry of Health Republic of Ghana. 2017.
  119. Atinga RA, Yarney L, Gavu NM. Factors influencing long-term medication non-adherence among diabetes and hypertensive patients in Ghana: A qualitative investigation. PloS One. 2018; 13(3):e0193995.
  120. Gill GV, Yudkin JS, Keen H, Beran D. The insulin dilemma in resource-limited countries. A way forward? Diabetologia. 2011; 54(1):19-24.
  121. Gotham D, Barber MJ, Hill A. Production costs and potential prices for biosimilars of human insulin and insulin analogues. BMJ Global Health. 2018;3:e000850.
  122. Nashilongo MM, Singu B, Kalemeera F, Mubita M, Naikaku E, Baker A, et al. Assessing adherence to antihypertensive therapy in primary health care in Namibia: Findings and implications. Cardiovasc Drugs Ther. 2017;31:565-578
  123. Fadare JO, Adeoti AO, Desalu OO, Enwere OO, Makusidi AM, Ogunleye O, et al. The prescribing of generic medicines in Nigeria: Knowledge, perceptions and attitudes of physicians. Expert Rev Harmacoecon Outcomes Res. 2016;16:639-50.
  124. Murphy A, Palafox B, Walli-Attaei M, Powell-Jackson T, Rangarajan S, Alhabib KF, et al. The household economic burden of non-communicable diseases in 18 countries. BMJ Global Health. 2020;5:e002040.
  125. Chow CK, Ramasundarahettige C, Hu W, AlHabib KF, Avezum A, Cheng X, et al. Availability and affordability of essential medicines for diabetes across high-income, middle-income, and low-income countries: A prospective epidemiological study. Lancet Diabetes Endocrinol. 2018;6:798-808.
  126. Government of the kingdom of Swaziland ministry of health, the president’s emergency plan for aids relief, usaid, and strengthening pharmaceutical systems (sps) program. Standard treatment guidelines and essential medicines list of common medical conditions in the Kingdom of Swaziland. 2012.
  127. Makadzange K. Universal health coverage: Leaving no one behind in the kingdom of Eswatini. 2019.
  128. Cerf ME. Sustainable development goal integration, interdependence, and implementation: The environment-economic-health nexus and universal health coverage. Glob Chall. 2019;3:1900021.
  129. Pillay Y, Manthalu G, Solange H, Okello V, Hildebrand M, Sundewall J, et al. Health benefit packages: Moving from aspiration to action for improved access to quality SRHR through UHC reforms. Sex Reprod Health Matters. 2020;28:1842152.
  130. Ncube NBQ, Knight L, Bradley HA, Schneider H, Laing R. Health system actors' perspectives of prescribing practices in public health facilities in Eswatini: A Qualitative Study. PloS one. 2020;15:e0235513.
  131. Chikowe I, Mwapasa V, Kengne AP. Analysis of rural health centres preparedness for the management of diabetic patients in Malawi. BMC Res Notes. 2018;11:267.
  132. Khuluza F, Haefele-Abah C. The availability, prices and affordability of essential medicines in Malawi: A cross-sectional study. PloS one. 2019;14:e0212125.
  133. Allain TJ, Mang'anda G, Kasiya M, Khomani P, Banda NP, Gonani A, et al. Use of an electronic medical record to monitor efficacy of diabetes care in out-patients in a central hospital in Malawi: Patterns of glycaemic control and lessons learned. Malawi Med J. 2017;29:322-326.
  134. Malawi Standard Treatment Guidelines (MSTG). Government of Malawi.2015.
  135. Meyer JC, Schellack N, Stokes J, Lancaster R, Zeeman H, Defty D, et al. Ongoing initiatives to improve the quality and efficiency of medicine use within the public healthcare system in South Africa; A preliminary study. Frontiers in pharmacology. 2017; 8:751.
  136. Minister for health, community development, gender, elderly and children. Ministry of Health Tanzania. 2017.
  137. Obakiro SB, Kiyimba K, Napyo A, Kanyike AM, Mayoka WJ, Nnassozi AG, et al. Appropriateness and affordability of prescriptions to diabetic patients attending a tertiary hospital in Eastern Uganda: A retrospective cross-sectional study. PloS one. 2021;16:e0245036.
  138. Kibirige D, Atuhe D, Kampiire L, Kiggundu DS, Donggo P, Nabbaale J, et al. Access to medicines and diagnostic tests integral in the management of diabetes mellitus and cardiovascular diseases in Uganda: Insights from the ACCODAD study. Int J Equity Health. 2017;16:154.
  139. Birabwa C, Bwambale MF, Waiswa P, Mayega RW. Quality and barriers of outpatient diabetes care in rural health facilities in Uganda-a mixed methods study. BMC Health Serv res. 2019;19:706.
  140. Bahendeka S, Mutungi G, Tugumisirize F, Kamugisha A, Nyangabyaki C, Wesonga R, et al. Healthcare delivery for paediatric and adolescent diabetes in low resource settings: Type 1 diabetes clinics in Uganda. Glob public health. 2019;14:1869-1883.
  141. Kyokunzire C, Matovu N. Factors associated with adherence to diabetes care recommendations among children and adolescents with type 1 diabetes: a facility-based study in two urban diabetes clinics in Uganda. Diabetes Metab Syndr Obes. 2018;11:93.
  142. Prevalence_of_diabetic_retinopathy_and_visual_impairment_in_patients_with_diabetes_mellitus_in_Zambia_through_the_implementation_of_a_mobile_diabetic_retinopathy_screening_project_in_the_Copperbelt_pr' target='_blank'>Lewis A.D, Hogg R.E, Chandran M, Musonda L, North L, Chakravarthy U, et al.   Prevalence of diabetic retinopathy and visual impairment in patients with diabetes mellitus in Zambia through the implementation of a mobile diabetic retinopathy screening project in the Copperbelt province: Across-sectional study. Eye. 2018;32(7):1201-1208.
  143. Olamoyegun MA, Raimi TH, Ala OA, Fadare JO. Mobile phone ownership and willingness to receive mhealth services among patients with diabetes mellitus in South-West, Nigeria. Pan Afr Med J. 2020;37.
  144. Bonoto BC, De Araújo VE, Godói IP, De Lemos LL, Godman B, Bennie M, et al. Efficacy of mobile apps to support the care of patients with diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials. JMIR m Health and U Health. 2017; 5(3):e4.
  145. Jemere AT, Yeneneh YE, Tilahun B, Fritz F, Alemu S, Kebede M. Access to mobile phone and willingness to receive mHealth services among patients with diabetes in Northwest Ethiopia: A cross-sectional study. BMJ Open. 2019; 9(1):e021766
  146. Insulin glargine market: By type (pre-filled syringe and single dose vial), by application (type 1 diabetes and type 2 diabetes), by distribution channel (hospital pharmacy, online sales, retail pharmacy and other distribution channels): Global industry perspective, comprehensive analysis and forecast, 2018-2025. Zion Market Research. 2019.
  147. Godman B. Biosimilars are becoming indispensable in the management of multiple diseases although concerns still exist. Bangladesh J Med Sci. 2021; 20(1):5-10.
  148. Davio K. After biosimilar deals, UK spending on adalimumab will drop by 75%. Center for biosimilars. 2018.
  149. Sandoz-A Novartis Division. Kenya is first country to launch ‘Novartis Access’, expanding affordable treatment options against chronic diseases.2015.
  150.  WHO guideline on country pharmaceutical pricing policies. World Health Organization. 2020.
  151. O’Mahony JF. Beneluxa: What are the prospects for collective bargaining on pharmaceutical prices given diverse health technology assessment processes?
  152. Singh S. Biocon’s Malaysia insulin glargine manufacturing facility receives EU GMP certification. 2019.
  153. Secretariat EA. East African community Covid-19 response plan. Arusha: East African community. 2020.
  154. A stepwise approach for the pharmaceutical industry to attain internationally recognised GMP standards. 2019.
  155. Colloca L, Panaccione R, Murphy TK. The clinical implications of nocebo effects for biosimilar therapy. Front Pharmacol. 2019;10:1372.
  156. Moorkens E, Godman B, Huys I, Hoxha I, Malaj A, Keuerleber S, et al. The expiry of humira® market exclusivity and the entry of adalimumab biosimilars in Europe: An overview of pricing and national policy measures. Front Pharmacol. 2021;11:1993.

Author Info

Brian Godman1,2,3*, Trudy Leong4, Abdullahi Rabiu Abubakar5, Amanj Kurdi1,6, Francis Kalemeera7, Godfrey Mutashambara Rwegerera8,9, Okwen Patrick10,11, Loveline Lum Niba10,12, Kamilou Ibrahim13, Adefolarin A Amu14, Patrick Matowa14, Joseph Acolatse15, Robert Incoom15, Israel Abebrese Sefah16,17, Sylvia Opanga18, Lisper Wangeci Njeri19, David Kimonge18, Margaret Oluka20, Ibrahim Chikowe21, Felix Khuluza21, Henry Phiri22, Dan Kibuule7, Ester Hango7, Ibrahim Haruna Sani23, Oliver Ombeva Malande24,25, Thereza Piloya-Were26, Luke Alutuli27, Aubrey Chichonyi Kalungia28, Blessmore Vimbai Chaibva29, Trust Zaranyika30, Mainul Haque31, Eleonora Allocati32, Stephen Campbell33,34, Eunice Twumwaa Adwubi35 and Olayinka O. Ogunleye36,37
 
1Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, United Kingdom
2Division of Public Health Pharmacy and Management, School of Pharmacy, Sefako Makgatho Health Sciences University, Pretoria, South Africa
3School of Pharmaceutical Sciences, University Sains Malaysia, Penang, Malaysia
4Essential Drugs Programme, South African National Department of Health, Pretoria, South Africa
5Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Bayero University, Kano, Nigeria
6Department of Pharmacology, College of Pharmacy, Hawler Medical University, Erbil, Iraq
7Department of Pharmacy Practice and Policy, Faculty of Health Sciences, University of Namibia, Windhoek, Namibia
8Department of Medicine, Sir Ketumile Masire Teaching Hospital, Gaborone, Botswana
9Department of Medicine, University of Botswana, Gaborone, Botswana
10Effective Basic Services (eBASE) Africa, Ndamukong Street, Bamenda, Cameroon, South Africa
11Department of Medicine, Adelaide University, Adelaide, Australia
12Department of Public Health, University of Bamenda, P.O. Box 39, Bambili, Cameroon
13Department of Medicine, Bali hospital, Bali, Cameroon
14Eswatini Medical Christian University, P.O Box A624, Swazi Plaza, Mbabane, South Africa
15Pharmacy Directorate, Cape Coast Teaching Hospital (CCTH), Cape Coast, Ghana
16Department Pharmacy, Keta Municipal Hospital, Ghana Health Service, Keta-Dzelukope, Ghana
17Department of Pharmacy Practice, School of Pharmacy, University of Health and Allied Sciences, Volta Region, Ghana
18Department of Pharmaceutics and Pharmacy Practice, School of Pharmacy, University of Nairobi, Nairobi, Kenya
19Department of Pharmacy, Kenyatta National Hospital, Nairobi, Kenya
20Department of Pharmacology and Pharmacognosy, School of Pharmacy, University of Nairobi, Nairobi, Kenya
21Department of Pharmacy, College of Medicine, Blantyre, Malawi
22Queen Elizabeth Central Hospital, Blantyre, Malawi
23Department of Pharmacology, College of Health Sciences, Yusuf Maitama Sule University (YUMSUK), PMB 3220, Kano, Nigeria
24Department of Child Health and Paediatrics, Egerton University, Nakuru, Kenya
25East Africa Centre for Vaccines and Immunization (ECAVI), Namela House, Naguru, Kampala, Uganda
26Department of Paediatric Endocrinologist, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda
27Department of Pharmacy, University Teaching Hospital Group, Lusaka, Zambia
28Department of Pharmacy, School of Health Sciences, University of Zambia, Lusaka, Zambia
29Department of Health Sciences, University of Pretoria, MoHCC, Rational Medicines Use Focal Person (RMUFP), Directorate of Pharmacy Services, Harare, Zimbabwe
30Department of Medicine, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe
31Unit of Pharmacology, Department of Medicine and Defence Health, Universiti Pertahanan Nasional Malaysia (National Defence University of Malaysia), Kem Sungai Besi, 57000 Kuala Lumpur, Malaysia
32Center for Health Regulatory Policies, Mario Negri IRCCS Pharmacological Research Institute, Pharmacological 'Mario Negri' IRCCS, Milan, Italy
33Centre for Primary Care, Division of Population Health, Health Services Research and Primary Care, University of Manchester, Manchester, M13 9PL, UK
34NIHR Greater Manchester Patient Safety Translational Research Centre, School of Health Sciences, University of Manchester, Manchester, UK
35Department of Management Science, Business School, University of Strathclyde, Glasgow G4 0QU, United Kingdom
36Department of Pharmacology, Therapeutics and Toxicology, Lagos State University College of Medicine, Ikeja, Lagos, Nigeria
37Department of Medicine, Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria
 

Citation: Godman B, Leong T, Abubakar AR, Kurdi A, Kalemeera F, Rwegerera GM, et al. (2021) Availability and Use of Long-Acting Insulin Analogues Including Their Biosimilars across Africa: Findings and Implications. Intern Med. 11:343.

Received: 13-Jul-2021 Accepted: 03-Aug-2021 Published: 15-Sep-2021 , DOI: 10.35248/2165-8048.21.11.343

Copyright: © 2021 Godman B, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Sources of funding : The authors declare they have no competing interests. This analysis was commissioned and paid for by the World Health Organization. The authors are totally responsible for the views expressed in this paper and they do not necessarily represent the decisions, policy or views of the World Health Organization.

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