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Reduced Insulin Use and Diabetes Complications Upon Introduction of Sglt-2 Inhibitors and Glp1-Receptor Agonists in Low- and Middle-Income Countries: A Microsimulation Publisher



Ali MK1 ; Aryal KK2 ; Atun R3, 4 ; Bahendeka SK5 ; Barnighausen T6, 7, 8 ; Basu S9 ; Beran DH10 ; Bicaba BW11 ; Bovet P12 ; Brant LCC13 ; Damasceno A14 ; Davies J15 ; Flood D16 ; Geldsetzer P17 Show All Authors
Authors
  1. Ali MK1
  2. Aryal KK2
  3. Atun R3, 4
  4. Bahendeka SK5
  5. Barnighausen T6, 7, 8
  6. Basu S9
  7. Beran DH10
  8. Bicaba BW11
  9. Bovet P12
  10. Brant LCC13
  11. Damasceno A14
  12. Davies J15
  13. Flood D16
  14. Geldsetzer P17
  15. Gurung MS2
  16. Guwatudde D18
  17. Houehanou C19
  18. Jorgensen JMA20
  19. Karki KB2
  20. Oh SK21
  21. Lipska K22
  22. Luo J23
  23. Malta DC13
  24. Mannegoehler J24
  25. Martins JS25
  26. Mayige MT26
  27. Moghaddam SS27, 28
  28. Mwalim O29
  29. Mwangi KJ30
  30. Norov B31
  31. Sibai AM32
  32. Teufel F33
  33. Theilmann M24, 34
  34. Vollmer S35
  35. Yudkin JS36
  36. Zhumadilov Z37
Show Affiliations
Authors Affiliations
  1. 1. Hubert Department of Global Health, Emory University, Atlanta, GA, United States
  2. 2. Nepal Health Research Council, Kathmandu, Nepal
  3. 3. Department of Global Health and Population, Harvard TH Chan School of Public Health, Boston, MA, United States
  4. 4. Department of Global Health and Social Science, Harvard Medical School, Boston, MA, United States
  5. 5. Uganda Diabetes Association, Kampala, Uganda
  6. 6. Heidelberg Institute of Global Health (HIGH), Faculty of Medicine, University Hospital, Heidelberg University, Heidelberg, Germany
  7. 7. Department of Global Health and Population, Harvard T.H. Chan School of Public Health, MA, United States
  8. 8. Africa Health Research Institute (AHRI), KwaZulu-Natal, Somkhele, South Africa
  9. 9. Clinical Product Development, Waymark, San Francisco, CA, United States
  10. 10. Geneva University Hospitals, University of Geneva, Geneva, Switzerland
  11. 11. Burkina Faso Ministry of Health, Ouagadougou, Burkina Faso
  12. 12. Institute of Social and Preventive Medicine, University of Lausanne, Lausanne, Switzerland
  13. 13. Federal University of Minas Gerais, Belo Horizonte, Brazil
  14. 14. Eduardo Mondlane University, Maputo, Mozambique
  15. 15. Stellenbosch University, South Africa and Institute of Applied Health Sciences, University of Birmingham, Birmingham, United Kingdom
  16. 16. Division of General Internal Medicine, University of Michigan, Ann Arbor, MI, United States
  17. 17. Department of Medicine, Stanford University, Palo Alto, CA, United States
  18. 18. Makerere University, School of Public Health, Kampala, Uganda
  19. 19. Regional Institute of Public Health, University of Abomey-Calavi, Cotonou, Benin
  20. 20. Danish Diabetes Academy, Odense University Hospital, Odense, Denmark
  21. 21. Division of Endocrinology, Brigham and Women’s Hospital, Boston, MA, United States
  22. 22. Department of Endocrinology, Yale University, New Haven, CT, United States
  23. 23. University of Pittsburgh, Pittsburgh, PA, United States
  24. 24. Harvard Medical School, Boston, MA, United States
  25. 25. University of Minho, Braga, Portugal
  26. 26. National Institute for Medical Research, Dar es Salaam, Tanzania
  27. 27. Kiel Institute for the World Economy, Kiel, Germany
  28. 28. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  29. 29. Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
  30. 30. Kenya Medical Research Institute, Nairobi, Kenya
  31. 31. National Center for Public Health, Ulaanbaatar, Mongolia
  32. 32. Faculty of Health Sciences, American University of Beirut, Lebanon
  33. 33. Heidelberg Institute of Global Health, Heidelberg University, Heidelberg, Germany
  34. 34. Division of Infectious Diseases, Brigham and Women’s Hospital, Boston, MA, United States
  35. 35. University of Goettingen, Goettingen, Germany
  36. 36. University College London, London, United Kingdom
  37. 37. Nazarbayev University School of Medicine, Astana, Kazakhstan

Source: PLoS Medicine Published:2025


Abstract

Background Diabetes mellitus, particularly type 2 diabetes, is a growing health concern in low- and middle-income countries (LMICs). The potential impact of newer diabetes medications, such as glucagon-like peptide 1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors, on insulin dosage and health outcomes in these settings is not well understood. Methods and findings We developed a microsimulation model to estimate the impact of treating patients with type 2 diabetes who use insulin with GLP-1 receptor agonists or SGLT-2 inhibitors in LMICs. The model utilized data from the Global Health and Population Project on Access to Care for Cardiometabolic Diseases (HPACC) dataset, encompassing surveys from 79 countries and clinical trial data to estimate insulin dose reduction. We incorporated weight-based insulin dosing formulas and hazard ratios for severe hypoglycemia, cardiovascular and renal outcomes, side effects of new therapies, and mortality. The primary outcome was the change in insulin dosage, and secondary outcomes were disability-adjusted life years (DALYs) lost per 1,000 person-years by diabetes complication (micro- and macro-vascular). Our results indicate that the addition of GLP-1 receptor agonists or SGLT-2 inhibitors could reduce insulin dosage by 8.2 IU/day (IQR: 6.9, 9.5) and 5.3 IU/day (IQR: 4.5, 6.2), respectively. The median DALYs lost per 1,000 person-years decreased from 2.20 (IQR: 1.49, 4.02) to 1.01 (IQR: 0.61, 1.86) with GLP-1 receptor agonists and 1.25 (IQR: 0.81, 2.29) with SGLT-2 inhibitors. Primary benefits arose from weight loss, decreased cardiorenal disease, and decreased mortality, with smaller DALY benefits from the prevention of severe hypoglycemia. Key limitations include the inability to differentiate between type 1 and type 2 diabetes in some datasets and reliance on assumptions from clinical trials conducted primarily in high-income countries. Conclusions The introduction of GLP-1 receptor agonists and SGLT-2 inhibitors for managing type 2 diabetes in LMICs could significantly reduce insulin dosage and associated health risks, leading to improved outcomes and reduced disability. These findings suggest that expanding access to these newer diabetes medications in LMICs could have substantial public health benefits. © 2025 Global Health & Population Project on Access to Care for Cardiometabolic Diseases (HPACC). 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.