Reduced insulin use and diabetes complications upon introduction of SGLT-2 inhibitors and GLP1-receptor agonists in low- and middle-income countries: A microsimulation

Ali M.K. Aryal K.K. Atun R. Bahendeka S.K. Bärnighausen T. Basu S. Beran D.H. Bicaba B.W. Bovet P. Brant L.C.C. Damasceno A. Davies J. Flood D. Geldsetzer P. Gurung M.S. Guwatudde D. Houehanou C. Jorgensen J.M.A. Karki K.B. Oh S.K. Lipska K. Luo J. Malta D.C. Manne-Goehler J. Martins J.S. Mayige M.T. Moghaddam S.S. Mwalim O. Mwangi K.J. Norov B. Sibai A.M. Teufel F. Theilmann M. Vollmer S. Yudkin J.S. Zhumadilov Z.
April 2025 Public Library of Science

PLoS Medicine
2025 #22 Issue 4 April

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.

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Hubert Department of Global Health, Emory University, Atlanta, GA, United States
Nepal Health Research Council, Kathmandu, Nepal
Department of Global Health and Population, Harvard TH Chan School of Public Health, Boston, MA, United States
Department of Global Health and Social Science, Harvard Medical School, Boston, MA, United States
Uganda Diabetes Association, Kampala, Uganda
Heidelberg Institute of Global Health (HIGH), Faculty of Medicine, University Hospital, Heidelberg University, Heidelberg, Germany
Department of Global Health and Population, Harvard T.H. Chan School of Public Health, MA, United States
Africa Health Research Institute (AHRI), KwaZulu-Natal, Somkhele, South Africa
Clinical Product Development, Waymark, San Francisco, CA, United States
Geneva University Hospitals, University of Geneva, Geneva, Switzerland
Burkina Faso Ministry of Health, Ouagadougou, Burkina Faso
Institute of Social and Preventive Medicine, University of Lausanne, Lausanne, Switzerland
Federal University of Minas Gerais, Belo Horizonte, Brazil
Eduardo Mondlane University, Maputo, Mozambique
Stellenbosch University, South Africa and Institute of Applied Health Sciences, University of Birmingham, Birmingham, United Kingdom
Division of General Internal Medicine, University of Michigan, Ann Arbor, MI, United States
Department of Medicine, Stanford University, Palo Alto, CA, United States
Makerere University, School of Public Health, Kampala, Uganda
Regional Institute of Public Health, University of Abomey-Calavi, Cotonou, Benin
Danish Diabetes Academy, Odense University Hospital, Odense, Denmark
Division of Endocrinology, Brigham and Women’s Hospital, Boston, MA, United States
Department of Endocrinology, Yale University, New Haven, CT, United States
University of Pittsburgh, Pittsburgh, PA, United States
Harvard Medical School, Boston, MA, United States
University of Minho, Braga, Portugal
National Institute for Medical Research, Dar es Salaam, Tanzania
Kiel Institute for the World Economy, Kiel, Germany
Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
Kenya Medical Research Institute, Nairobi, Kenya
National Center for Public Health, Ulaanbaatar, Mongolia
Faculty of Health Sciences, American University of Beirut, Lebanon
Heidelberg Institute of Global Health, Heidelberg University, Heidelberg, Germany
Division of Infectious Diseases, Brigham and Women’s Hospital, Boston, MA, United States
University of Goettingen, Goettingen, Germany
University College London, London, United Kingdom
Nazarbayev University School of Medicine, Astana, Kazakhstan

Hubert Department of Global Health
Nepal Health Research Council
Department of Global Health and Population
Department of Global Health and Social Science
Uganda Diabetes Association
Heidelberg Institute of Global Health (HIGH)
Department of Global Health and Population
Africa Health Research Institute (AHRI)
Clinical Product Development
Geneva University Hospitals
Burkina Faso Ministry of Health
Institute of Social and Preventive Medicine
Federal University of Minas Gerais
Eduardo Mondlane University
Stellenbosch University
Division of General Internal Medicine
Department of Medicine
Makerere University
Regional Institute of Public Health
Danish Diabetes Academy
Division of Endocrinology
Department of Endocrinology
University of Pittsburgh
Harvard Medical School
University of Minho
National Institute for Medical Research
Kiel Institute for the World Economy
Endocrinology and Metabolism Research Center
Muhimbili University of Health and Allied Sciences
Kenya Medical Research Institute
National Center for Public Health
Faculty of Health Sciences
Heidelberg Institute of Global Health
Division of Infectious Diseases
University of Goettingen
University College London
Nazarbayev University School of Medicine

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