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      Estimated Sustainable Cost-Based Prices for Diabetes Medicines

      research-article
      , PhD 1 , 2 , 3 , , , MBBS 4 , 5 , , MBBS 5 , , MPH 5
      JAMA Network Open
      American Medical Association

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          Key Points

          Question

          What could prices of insulins, sodium-glucose cotransporter 2 inhibitors (SGLT2Is), and glucagonlike peptide 1 agonists (GLP1As) be if they were closer to the cost of production?

          Findings

          In this economic evaluation of manufacturing costs, estimated cost-based prices per month were US $1.30 to $3.45 for SGLT2Is (except canagliflozin), and $0.75 to $72.49 for GLP1As, substantially lower than current market prices in nearly all comparisons. Twice-daily mixed human insulin NPH could cost $61 per year, while basal-bolus treatment with insulin glargine and aspart could cost $111 per year, with reusable pen formulations having the lowest estimated prices.

          Meaning

          The findings of this study suggest that insulins, SGLT2Is, and GLP1As can likely be manufactured for prices far below current prices, enabling wider access.

          Abstract

          Importance

          The burden of diabetes is growing worldwide. The costs associated with diabetes put substantial pressure on patients and health budgets, especially in low- and middle-income countries. The prices of diabetes medicines are a key determinant for access, yet little is known about the association between manufacturing costs and current market prices.

          Objectives

          To estimate the cost of manufacturing insulins, sodium-glucose cotransporter 2 inhibitors (SGLT2Is), and glucagonlike peptide 1 agonists (GLP1As), derive sustainable cost-based prices (CBPs), and compare these with current market prices.

          Design, Setting, and Participants

          In this economic evaluation, the cost of manufacturing insulins, SGLT2Is, and GLP1As was modeled. Active pharmaceutical ingredient cost per unit (weighted least-squares regression model using data from a commercial database of trade shipments, data from January 1, 2016, to March 31, 2023) was combined with costs of formulation and other operating expenses, plus a profit margin with an allowance for tax, to estimate CBPs. Cost-based prices were compared with current prices in 13 countries, collected in January 2023 from public databases. Countries were selected to provide representation of different income levels and geographic regions based on the availability of public databases.

          Main Outcomes and Measures

          Estimated CBPs; lowest current market prices (2023 US dollars).

          Results

          In this economic evaluation of manufacturing costs, estimated CBPs for treatment with insulin in a reusable pen device could be as low as $96 (human insulin) or $111 (insulin analogues) per year for a basal-bolus regimen, $61 per year using twice-daily injections of mixed human insulin, and $50 (human insulin) or $72 (insulin analogues) per year for a once-daily basal insulin injection (for type 2 diabetes), including the cost of injection devices and needles. Cost-based prices ranged from $1.30 to $3.45 per month for SGLT2Is (except canagliflozin: $25.00-$46.79) and from $0.75 to $72.49 per month for GLP1As. These CBPs were substantially lower than current prices in the 13 countries surveyed.

          Conclusions and Relevance

          High prices limit access to newer diabetes medicines in many countries. The findings of this study suggest that robust generic and biosimilar competition could reduce prices to more affordable levels and enable expansion of diabetes treatment globally.

          Abstract

          This economic evaluation examines the health expenditures related to medicines used for treatment of diabetes worldwide.

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          Most cited references26

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          Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

          Summary Background In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and development investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding Bill & Melinda Gates Foundation.
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            Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007–2017

            Background Cardiovascular disease (CVD) is a common comorbidity in type 2 diabetes (T2DM). CVD’s prevalence has been growing over time. Purpose To estimate the current prevalence of CVD among adults with T2DM by reviewing literature published within the last 10 years (2007–March 2017). Methods We searched Medline, Embase, and proceedings of major scientific meetings for original research documenting the prevalence of CVD in T2DM. CVD included stroke, myocardial infarction, angina pectoris, heart failure, ischemic heart disease, cardiovascular disease, coronary heart disease, atherosclerosis, and cardiovascular death. No restrictions were placed on country of origin or publication language. Two reviewers independently searched for articles and extracted data, adjudicating results through consensus. Data were summarized descriptively. Risk of bias was examined by applying the STROBE checklist. Results We analyzed data from 57 articles with 4,549,481 persons having T2DM. Europe produced the most articles (46%), followed by the Western Pacific/China (21%), and North America (13%). Overall in 4,549,481 persons with T2DM, 52.0% were male, 47.0% were obese, aged 63.6 ± 6.9 years old, with T2DM duration of 10.4 ± 3.7 years. CVD affected 32.2% overall (53 studies, N = 4,289,140); 29.1% had atherosclerosis (4 studies, N = 1153), 21.2% had coronary heart disease (42 articles, N = 3,833,200), 14.9% heart failure (14 studies, N = 601,154), 14.6% angina (4 studies, N = 354,743), 10.0% myocardial infarction (13 studies, N = 3,518,833) and 7.6% stroke (39 studies, N = 3,901,505). CVD was the cause of death in 9.9% of T2DM patients (representing 50.3% of all deaths). Risk of bias was low; 80 ± 12% of STROBE checklist items were adequately addressed. Conclusions Globally, overall CVD affects approximately 32.2% of all persons with T2DM. CVD is a major cause of mortality among people with T2DM, accounting for approximately half of all deaths over the study period. Coronary artery disease and stroke were the major contributors.
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              Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

              The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the previous consensus statements on the management of hyperglycaemia in type 2 diabetes in adults, published since 2006 and last updated in 2019. The target audience is the full spectrum of the professional healthcare team providing diabetes care in the USA and Europe. A systematic examination of publications since 2018 informed new recommendations. These include additional focus on social determinants of health, the healthcare system and physical activity behaviours including sleep. There is a greater emphasis on weight management as part of the holistic approach to diabetes management. The results of cardiovascular and kidney outcomes trials involving sodium–glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, including assessment of subgroups, inform broader recommendations for cardiorenal protection in people with diabetes at high risk of cardiorenal disease. After a summary listing of consensus recommendations, practical tips for implementation are provided. Graphical abstract Supplementary Information The online version of this article (10.1007/s00125-022-05787-2) contains peer-reviewed but unedited supplementary material.
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                Author and article information

                Journal
                JAMA Netw Open
                JAMA Netw Open
                JAMA Network Open
                American Medical Association
                2574-3805
                27 March 2024
                March 2024
                27 March 2024
                : 7
                : 3
                : e243474
                Affiliations
                [1 ]Yale Collaboration for Regulatory Rigor, Integrity, and Transparency (CRRIT), New Haven, Connecticut
                [2 ]Program on Regulation, Therapeutics, and Law, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, and Harvard Medical School, Boston, Massachusetts
                [3 ]Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
                [4 ]King’s College Hospital, London, United Kingdom
                [5 ]Médecins Sans Frontières Access Campaign, Geneva, Switzerland
                Author notes
                Article Information
                Accepted for Publication: January 29, 2024.
                Published: March 27, 2024. doi:10.1001/jamanetworkopen.2024.3474
                Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2024 Barber MJ et al. JAMA Network Open.
                Corresponding Author: Melissa J. Barber, PhD, Edward S. Harkness Memorial Hall A, 367 Cedar St, Room 406, New Haven, CT 06510 ( melissa.barber@ 123456yale.edu ).
                Author Contributions: Drs Barber and Gotham had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
                Concept and design: All authors.
                Acquisition, analysis, or interpretation of data: Barber, Gotham.
                Drafting of the manuscript: Barber, Gotham.
                Critical review of the manuscript for important intellectual content: All authors.
                Statistical analysis: Barber.
                Obtained funding: Barber, Bygrave, Cepuch.
                Administrative, technical, or material support: Barber, Bygrave, Cepuch.
                Supervision: Barber, Bygrave.
                Conflict of Interest Disclosures: Dr Barber reported receiving personal fees from Médecins Sans Frontières during the conduct of the study and personal fees from the World Health Organization outside the submitted work. Dr Gotham reported receiving personal fees from Médecins Sans Frontières during the conduct of the study and has previously received payments (unrelated to this work) from the World Health Organization, the Medicines Patent Pool, Treatment Action Group, STOPAIDS UK, Global Justice Now, the World Intellectual Property Organization, and the Ada Lovelace Institute. Ms Bygrave reported being an employee of Médecins Sans Frontières during the conduct of the study. Ms Cepuch reported being an employee of Médecins Sans Frontières during the conduct of the study. No other disclosures were reported.
                Funding/Support: This study was funded by Médecins Sans Frontières (Doctors Without Borders) Access Campaign.
                Role of the Funder/Sponsor: Médecins Sans Frontières had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
                Data Sharing Statement: See Supplement 2.
                Additional Contributions: We thank our colleagues at Médecins Sans Frontières; Kevin Croke, PhD (Harvard T.H. Chan School of Public Health), Margaret McConnell, PhD (Harvard T.H. Chan School of Public Health), and Ameet Sarpatwari, JD, PhD (Harvard Medical School), for thoughtful comments; as well as the anonymous industry experts who provided cost data. Thanks to Hannibal Taubes, AB, PhD candidate in East Asian Languages and Cultures, University of California, Berkeley, for support in translating documents from Chinese (uncompensated).
                Article
                zoi240154
                10.1001/jamanetworkopen.2024.3474
                10973901
                38536176
                f88af9b1-481b-4a20-9416-793d5198301e
                Copyright 2024 Barber MJ et al. JAMA Network Open.

                This is an open access article distributed under the terms of the CC-BY License.

                History
                : 5 October 2023
                : 29 January 2024
                Categories
                Research
                Original Investigation
                Online Only
                Diabetes and Endocrinology

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