Management of type 2 diabetes mellitus in overweight patients: an updated review

Background. Innovations have been recently proposed in the treatment of type 2 diabetes. Metformin is recommended as a first-line drug now as before; but indications for the use of glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors are expanding. Review articles do not always mention that the hypoglycemic effect of glucagon-like peptide 1 receptor agonists is associated with the stimulation of the endocrine function of beta cells, which may be depleted over time.

Objective. Unbiased comparison of the effectiveness and possible side effects of drugs used in the treatment of type 2 diabetes mellitus with overweight.

Materials and methods. Review of Russian and international literature using the databases elibrary.ru, PubMed and Google Scholar, as well as library catalogs.

Results. A brief overview of recent publications on sugar-lowering drugs that can be used in type 2 diabetes with overweight patients is presented. The effect of drugs on body weight and beta cell function, as well as relative cost of the treatment is discussed. Special attention is paid to the following groups of medicines. Glucagon-like peptide 1 receptor agonists stimulate the secretion of insulin, lowering appetite and the gastrointestinal motility, thus promoting weight loss. The relatively high cost of glucagon-like peptide 1 receptor agonists and subcutaneous administration are pointed out. Oral semaglutide is the only glucagon-like peptide 1 receptor agonist preparation used for the oral intake. Sodium-glucose cotransporter 2 inhibitors reduce renal glucose reabsorption, excrete glucose in the urine, lower blood pressure, and promote weight loss. Glycemic control is thus maintained in the long term. Weight loss can also be expected from intestinal alpha-glucosidase inhibitors (acarbose), which inhibit the digestion and absorption of complex carbohydrates in the intestine. The hypoglycemic effect of the drugs of last two groups (as well as metformin) is not associated with the stimulation beta cells, which can be depleted by prolonged stimulation. Combination therapy using sugar-lowering and anorexigenic drugs is discussed.

Conclusion. Complications of diabetes mellitus are caused not only by hyperglycemia, but also by dyslipidemia, hypertension, physical inactivity, smoking and other factors, which requires an individual approach to drug therapy and lifestyle modification.

1. American Diabetes Association Professional Practice Committee. 8. Obesity and Weight Management for the Prevention and Treatment of Type 2 Diabetes: Standards of Care in Diabetes-2025. Diabetes Care. 2025; 48 (1 Suppl 1): S167-S180. DOI: 10.2337/dc25-S008.

2. American Diabetes Association Professional Practice Committee. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2025. Diabetes Care. 2025; 48 (1 Suppl 1): S181-S206. DOI: 10.2337/dc25-S009.

3. Jargin S. V. Recent advances in the treatment of type 2 diabetes mellitus with obesity. Lechaschi Vrach. 2019; (4): 84-86. (In Russ.)

4. Abbasi M., Heath B., McGinness L. Advances in metformin-delivery systems for diabetes and obesity management. Diabetes Obes Metab. 2024; 26 (9): 3513-3529. DOI: 10.1111/dom.15759.

5. Anderson J. E., Thieu V. T., Boye K. S., Hietpas R. T., Garcia-Perez L. E. Dulaglutide in the treatment of adult type 2 diabetes: a perspective for primary care providers. Postgrad Med. 2016; 128 (8): 810-821. DOI: 10.1080/00325481.2016.1218260.

6. Jendle J., Grunberger G., Blevins T., et al. Efficacy and safety of dulaglutide in the treatment of type 2 diabetes: a comprehensive review of the dulaglutide clinical data focusing on the AWARD phase 3 clinical trial program. Diabetes Metab Res Rev. 2016; 32 (8): 776-790. DOI: 10.1002/dmrr.2810.

7. Hussain M., Miras A. D. Peptide hormone analogue-based pharmacotherapy for obesity is effective: What is the evidence on hard end points and the long-term course? Chirurgie (Heidelb). 2025. DOI: 10.1007/s00104-025-02402-z. Epub ahead of print.

8. Kasagga A., Rebellow D., Hashmi T., Husami M. Y., Lama P., Arul Selvan K., Nakasagga K. Comparative efficacy and tolerability of tirzepatide versus semaglutide at varying doses for weight loss in non-diabetic adults with obesity: a network meta-analysis of randomized controlled trials. Cureus. 2025; 17 (8): e90335. DOI: 10.7759/cureus.90335.

9. Shestakova M. V., Bashlykova R. O. The perspectives in obesity and type 2 diabetes therapy: the present and future of incretin therapy. Ter Arkh. 2025; 97 (10): 823-829. DOI: 10.26442/00403660.2025.10.203366. (In Russ.)

10. Rothberg A. E., Ard J. D., Gudzune K. A., Herman W. H. Obesity Management for the Treatment of Type 2 Diabetes. 2024 May 1. In: Lawrence J. M., Casagrande S. S., Herman W. H., Wexler D. J., Cefalu W. T., editors. Diabetes in America. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). 2023.

11. Apovian C. M., Okemah J., O’Neil P. M. Body weight considerations in the management of type 2 diabetes. Adv Ther. 2019; 36 (1): 44-58. DOI: 10.1007/s12325-018-0824-8.

12. Indovina F., Falcetta P., Del Prato S. Type 2 diabetes mellitus. From the start – combination therapy. Diabetes Mellitus. 2018; 21 (5): 386-394. DOI: 10.14341/DM9867.

13. Rea N., Ramdass P. V. A. K. GLP-1 receptor agonists and pancreatic beta cell apoptosis in diabetes mellitus: a systematic review and meta-analysis of preclinical studies. Front Clin Diabetes Healthc. 2025; 6: 1579961. DOI: 10.3389/fcdhc.2025.1579961.

14. Inoue K., Maeda N., Fujishima Y., et al. Long-term impact of liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, on body weight and glycemic control in Japanese type 2 diabetes: an observational study. Diabetol Metab Syndr. 2014; 6 (1): 95. DOI: 10.1186/1758-5996-6-95.

15. Ponzani P. Long-term effectiveness and safety of liraglutide in clinical practice. Minerva Endocrinol. 2013; 38 (1): 103-112.

16. Abdulreda M. H., Rodriguez-Diaz R., Caicedo A., Berggren P. O. Liraglutide compromises pancreatic β Cell function in a humanized mouse model. Cell Metab. 2016; 23 (3): 541-546. DOI: 10.1016/j.cmet.2016.01.009.

17. Aston-Mourney K., Hull R. L., Zraika S., et al. Exendin-4 increases islet amyloid deposition but offsets the resultant beta cell toxicity in human islet amyloid polypeptide transgenic mouse islets. Diabetologia. 2011; 54 (7): 1756-1765. DOI: 10.1007/s00125-011-2143-3.

18. Butler A. E., Campbell-Thompson M., Gurlo T., et al. Marked expansion of exocrine and endocrine pancreas with incretin therapy in humans with increased exocrine pancreas dysplasia and the potential for glucagon-producing neuroendocrine tumors. Diabetes. 2013; 62 (7): 2595-2604. DOI: 10.2337/db12-1686.

19. Wysham C. H., Pilon D., Ingham M., et al. HbA1c control and cost-effectiveness in patients with type 2 diabetes mellitus initiated on canagliflozin or a glucagon-like peptide 1 receptor agonist in a realworld setting. Endocr Pract. 2018; 24 (3): 273-287. DOI: 10.4158/EP-2017-0066.

20. Consoli A., Formoso G., Baldassarre M. P. A., Febo F. A comparative safety review between GLP-1 receptor agonists and SGLT2 inhibitors for diabetes treatment. Expert Opin Drug Saf. 2018; 17 (3): 293-302. DOI: 10.1080/14740338.2018.1428305.

21. Imprialos K. P., Stavropoulos K., Stavropoulos N., et al. Sodium-glucose cotransporter 2 inhibitors: Impact on body weight and blood pressure compared with other antidiabetic drugs. Cardiovasc Hematol Disord Drug Targets. 2018; 18 (2): 104-113. DOI: 10.2174/1871529X18666180206144342.

22. Hussein H., Zaccardi F., Khunti K., et al. Cardiovascular efficacy and safety of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists: a systematic review and network meta-analysis. Diabet Med. 2019; 36 (4): 444-452. DOI: 10.1111/dme.13898.

23. Bonikowska K., Magnusson P., Sjöholm Å. Life-threatening ketoacidosis in patients with type 2 diabetes on LCHF diet. Lakartidningen. 2018; 115.

24. Yuan Z., DeFalco F. J., Ryan P. B., et al. Risk of lower extremity amputations in people with type 2 diabetes mellitus treated with sodium-glucose co-transporter-2 inhibitors in the USA: A retrospective cohort study. Diabetes Obes Metab. 2018; 20 (3): 582-589. DOI: 10.1111/dom.13115.

25. Ryan P. B., Buse J. B., Schuemie M. J., et al. Comparative effectiveness of canagliflozin, SGLT2 inhibitors and non-SGLT2 inhibitors on the risk of hospitalization for heart failure and amputation in patients with type 2 diabetes mellitus: A real-world meta-analysis of 4 observational databases (OBSERVE4D). Diabetes Obes Metab. 2018; 20 (11): 2585-2597. DOI: 10.1111/dom.13424.

26. Ueda P., Svanström H., Melbye M., Eliasson B., Svensson A. M., Franzén S., Gudbjörnsdottir S., Hveem K., Jonasson C., Pasternak B. Sodium glucose cotransporter 2 inhibitors and risk of serious adverse events: nationwide register based cohort study. BMJ. 2018; 363: k4365. DOI: 10.1136/bmj.k4365.

27. Fadini G. P., Avogaro A. SGLT2 inhibitors and amputations in the US FDA Adverse Event Reporting System. Lancet Diabetes Endocrinol. 2017; 5: 680-681. DOI: 10.1016/S2213-8587(17)30257-7.

28. Schnell O., Weng J., Sheu W. H., et al. Acarbose reduces body weight irrespective of glycemic control in patients with diabetes: results of a worldwide, non-interventional, observational study data pool. J Diabetes Complications. 2016; 30 (4): 628-37. DOI: 10.1016/j.jdiacomp.2016.01.023.

29. Kwon Y., Kim H. J., Park S., Park Y. G., Cho K. H. Body mass index-related mortality in patients with type 2 diabetes and heterogeneity in obesity paradox studies: a dose-response meta-analysis. PLoS One. 2017; 12 (1): e0168247. DOI: 10.1371/journal.pone.0168247.

30. Hanefeld M., Fleischmann H., Siegmund T., Seufert J. Timely insulin therapy in type 2 diabetes within the framework of individualised treatment: 2020 update. Diabetes Ther. 2020; 11 (8): 1645-1666. DOI: 10.1007/s13300-020-00855-5.

31. Riddle M. C., Gerstein H. C., Holman R.R., Inzucchi S. E., Zinman B., Zoungas S., Cefalu W. T. A1C Targets Should Be Personalized to Maximize Benefits While Limiting Risks. Diabetes Care. 2018; 41 (6): 1121-1124. DOI: 10.2337/dci18-0018.

32. Jargin S. V. Insulin index of food products, its role in type 2 diabetes mellitus in overweight patients. Mezhdunarodnyi endokrinologicheskii zhurnal. 2021; 17 (7): 589-591. DOI: 10.22141/2224-0721.17.7.2021.244977. (In Russ.)

33. Perelló M. Critical Insights Into LEAP2 Biology and Physiological Functions: Potential Roles Beyond Ghrelin Antagonism. Endocrinology. 2025; 166 (2): bqaf011. DOI: 10.1210/endocr/bqaf011.

34. Williams D. M., Nawaz A., Evans M. Drug Therapy in Obesity: A Review of Current and Emerging Treatments. Diabetes Ther. 2020; 11 (6): 1199-1216. DOI: 10.1007/s13300-020-00816-y