Possibilities of early combination therapy with sitagliptin and metformin in the correction of metabolic disorders in patients with type 2 diabetes mellitus

• Alexander S. Ametov
• Dinara G. Gusenbekova
• Olga P. P'yanykh

Abstract

The current task of modern diabetology remains the search for an optimal therapeutic approach that increases the efficiency of treatment in patients with type 2 diabetes. Monotherapy with glucose-lowering drugs does not always lead to the achievement of target values of glycemia, and therefore it is necessary to intensify therapy with the use of two and three drugs, which leads to a decrease in patient compliance. The article describes the main pathogenetic mechanisms of development and progression of the disease, presents the results of studies demonstrating the benefits of early combination therapy with sitagliptin and metformin. Recently, a fixed combination of sitagliptin and prolonged release metformin has been developed with the possibility of once daily use that may increase adherence to therapy.

Keywords:diabetes mellitus type 2, obesity, sitagliptin, metformin

References

1. IDF Diabetes Аtlas. 8th ed. 2017.

2. Minokoshi Y., et al. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature. 2002; 415 (6869): 339-43.

3. Yoon M.J., et al. Adiponectin increases fatty acid oxidation in skeletal muscle cells by sequential activation of AMP-activated protein kinase, p38 mitogen-activated protein kinase, and peroxisome proliferator activated receptor α. Diabetes. 2006; 55 (9): 2562-70.

4. Lamers D., et al. Dipeptidyl peptidase 4 is a novel adipokine potentially linking obesity to the metabolic syndrome. Diabetes. 2011; 60 (7): 1917-25.

5. Sell H., et al. Adipose dipeptidyl peptidase-4 and obesity: correlation with insulin resistance and depot-specifi c release from adipose tissue in vivo and in vitro. Diabetes Care. 2013; 36 (12): 4083-90.

6. Ametov A.S. Diabetes mellitus type 2. Problems and solutions. 3rd edition, revision and supplement. Vol. 1. Moscow: GEOTAR-Media, 2015: 92-119. (in Russian)7. DeFronzo R. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009; 58 (4): 773-95.

8. Drucker D. The biology of incretin hormones. Cell Metab. 2006; 3: 153-65.

9. Drucker D., Nauck M. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006; 368: 1696-705.

10. Meier J., Nauck M. Incretins and the development of type 2 diabetes. Curr Diab Rep. 2006; 6: 194-201.

11. Meier J., et al. Reduced insulinotropic effect of gastric inhibitory polypeptide in first degree relatives of patients with type 2 diabetes. Diabetes. 2001; 50: 2497-504.

12. Hojberg P.V., et al. Four weeks of near-normalisation of blood glucose improves the insulin response to glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes. Diabetologia.2009; 52: 199-207.

13. Nauck M.A., et al. Incretin-based therapies. Viewpoints on the way to consensus. Diabetes Care. 2009; 32 (suppl 2): 223-31.

14. Van Genugten R., et al. Extra-pancreatic effects of incretin-based therapies: potential benefit for cardiovascular-risk management in type 2 diabetes. Diabetes Obes Metab. 2013; 15 (7): 593-606.

15. Derosa G., et al. Effects of a combination of sitagliptin plus metformin vs metformin monotherapy on glycemic control, p-cell function and insulin resistance in type 2 diabetic patients. Diabetes Res Clin Pract. 2012; 98 (1): 51-60.

16. Aschner P., et al. Insulin glargine versus sitagliptin in insulin-naive patients with type 2 diabetes mellitus uncontrolled on metformin (EASIE): a multicentre, randomised open-label trial. Lancet. 2012; 379 (9833): 2262-9.

17. Antsiferov M.B., Ametov A.S. Innovative Hypoglycemic Therapy: A New Strategy For An Old Problem. Farmateka [Pharmateca]. 2013; 258 (5): 1-9. (in Russian)

18. Melanie J., et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2018; 61: 2461-98.

19. Frias J.P., et al. Double-blind, randomized clinical trial assessing the efficacy and safety of early initiation of sitagliptin during metformin uptitration in the treatment of patients with type 2 diabetes: The CompoSIT-M study. Diabetes Obes Metab. 2019; 21 (5): 1128-35.

20. Scott R., et al. A randomized clinical trial of the efficacy and safety of sitagliptin compared with dapagliflozin in patients with type 2 diabetes mellitus and mild renal insufficiency: The CompoSIT-R study. Diabetes Obes Metab. 2018; 20 (12): 2876-884.

21. Ametov A.S., Gusenbekova D.G. The role of dipeptidyl peptidase 4 inhibitors in fat metabolism in patients with type 2 diabetes and obesity. Sakharnyy diabet [Diabetes Mellitus]. 2015; 18 (3); 85-92. (in Russian)

22. Ametov A.S., Gusenbekova D.G. DPP-4-inhibitors and fat metabolism in patients with type 2 diabetes. www.intechopen.com/books/diabetes-and-its-com-plications/dpp-4-inhibitors-and-fatmetabolism-in-patients-with-type-2-diabetes

23. Ametov A.S., Gusenbekova D.G. Influence of IDPP-4 on fat metabolism in patients with type 2 diabetes. Int J Clin Exp Med Sci. 2018; 4 (6): 78-86.

24. Instruction for medical use of the drug Janumet long. (in Russian)

All articles in our journal are distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0 license)