Practical Applications of Russian DPP4 Inhibitor Gosogliptin in “Palitra” Large-Scale Observational Study

BACKGROUND: To date, the results of Metformin, Gosogliptin and combination thereof have not been studied on a large patient population with type 2 diabetes mellitus (DM2), including comorbid patients, in real clinical settings in the Russian Federation.

AIM: The aim is to evaluate the efficacy, safety, treatment adherence and satisfaction of patients with DM2 with the use of Metformin and Gosogliptin sugar-lowering drugs and combination thereof in routine clinical practice.

MATERIALS AND METHODS: The nationwide PALITRA multicenter observational study was conducted among patients with DM2 who were prescribed therapy with Metformin or Gosogliptin or combination thereof in everyday clinical practice. Groups were formed according to the sugar-lowering drug administered; a total of 5741 patients aged 18 to 65 years with DM2 and a wide comorbidity profile participated. The observation period was 6 months. Body weight, body mass index (BMI), blood pressure (BP), glycated hemoglobin (HbA_1c) level, glycemic parameters, and biochemical parameters (ALT, AST and plasma creatinine) were recorded initially and 3 and 6 months after the initiation of therapy with the study drugs. Adherence to therapy and patient and physician satisfaction with the treatment were assessed using Likert scale.

RESULTS: HbA1c level decreased by 1.03% in the Metformin monotherapy group and by 0.95% in the Gosogliptin monotherapy and Metformin and Gosogliptin combination therapy groups by Week 24. By the end of the study, 49.6% of patients with DM2 reached the target HbA_1c level (<7.0%). The proportion of patients with HbA_1c level <7.0% was 61.0% in the Metformin group, 47.75% and 47.2% in the Gosogliptin and Metformin/Gosogliptin dual combination therapy groups, respectively. The incidence of hypoglycemic episodes was very low throughout the whole period of observation, during which body weight decreased slightly. High satisfaction of patients and physicians with DM2 treatment was shown. This was reflected by high Likert scale scores.

CONCLUSION: It has been proved that Metformin, Gosogliptin and the combination of Metformin and Gosogliptin were highly effective and safe (low incidence of hypoglycemia and no effect on body weight), and patients and physicians had been satisfied with the sugar-lowering therapy in a sufficient number of Russian patients with DM2 and a wide comorbidity profile.

1. Dedov II, Shestakova MV, Vikulova OK, et al. Diabetes mellitus in the Russian Federation: dynamics of epidemiological parameters according to the Federal Diabetes Mellitus Register for the period 2010–2022. Diabetes Mellitus. 2023;26(2):104-123 (In Russ.). doi: https://doi.org/10.14341/DM13035

2. Harding JL, Pavkov ME, Magliano DJ, et al. Global trends in diabetes complications: a review of current evidence. Diabetologia. 2019;62:3-16. doi: https://doi.org/10.1007/s00125-018-4711-2

3. Carr RD. Drug development from the bench to the pharmacy: with special reference to dipeptidyl peptidase-4 inhibitor development. Diabet Med. 2016;33:718–22. doi: https://doi.org/10.1111/dme.13066

4. Deacon CF. Physiology and pharmacology of DPP-4 in glucose homeostasis and the treatment of type 2 diabetes. Front Endocrinol (Lausanne). 2019;10:80. doi: https://doi.org/10.3389/fendo.2019.00080

5. Godinho R, Mega C, Teixeira-de-Lemos E, et al. The Place of Dipeptidyl Peptidase-4 Inhibitors in Type 2 Diabetes Therapeutics: A «Me Too» or «the Special One» Antidiabetic Class? Journal of Diabetes Research. 2015;2015:1-28. doi: https://doi.org/10.1155/2015/806979

6. Craddy P, Palin HJ, Johnson KI. Comparative effectiveness of dipeptidylpeptidase-4 inhibitors in type 2 diabetes: a systematic review and mixed treatment comparison // Diabetes Ther. 2014;5(1):1–41. doi: https://doi.org/10.1007/s13300-014-0061-3

7. Standards of specialized diabetes care. 11th edition (expanded edition) / Edited by Dedov I.I., Shestakova M.V., Mayorov A.Yu. — Moscow; 2023 (In Russ.).]. doi: https://doi.org/10.14341/DM12802

8. Chernikova NA, Knyshenko OA. Contribution of type 4 dipeptidyl peptidase inhibitors to real-world management of type 2 diabetes mellitus. Russian Medical Inquiry. 2023;7(9):2–8 (In Russ.). doi: https://doi.org/10.32364/2587-6821-2023-7-9-5

9. Martsevich SY, Kutishenko NP, Lukina YV, et al. Observation studies and registers. Their quality and role in modern evidence-based medicine. Cardiovascular Therapy and Prevention. 2021;20(2):2786 (In Russ.). doi: https://doi.org/10.15829/1728-8800-2021-2786

10. Schneeweiss S, Patorno E. Conducting Real-world Evidence Studies on the Clinical Outcomes of Diabetes Treatments. Endocr Rev. 2021;42(5):658-690. doi: https://doi.org/10.1210/endrev/bnab007

11. Saisho Y. Use of Diabetes Treatment Satisfaction Questionnaire in Diabetes Care: Importance of Patient-Reported Outcomes. Int J Environ Res Public Health 2018;15(5):947. doi: https://doi.org/10.3390/ijerph15050947

12. Merifatin. https://grls.minzdrav.gov.ru/Grls_View_v2.aspx?routingGuid=16349b79-4771-4d7c-9406-b384568e6350

13. Saterex. https://grls.minzdrav.gov.ru/Grls_View_v2.aspx?routingGuid=b9cacc57-e41f-40a6-bdf5- 2ec1163c649a

14. ElSayed NA, Aleppo G, Aroda VR. 6. Glycemic Targets: Standards of Care in Diabetes-2023. Diabetes Care. 2023;46(Suppl 1):S97-S110. doi: https://doi.org/10.2337/dc23-S006

15. Sidorov AV. Clinical pharmacology of dipeptidyl peptidase 4 inhibitors: a comparative review. Effective Pharmacotherapy. 2020;16(25):24–48. (In Russ.).] doi: https://doi.org/10.33978/2307-3586-2020-16-25-24-48

16. Galstyan KO, Nedosugova LV, Petunina NA, et al. First Russian DPP4 inhibitor Gosogliptin versus Vildagliptin in the treatment of patients with type 2 diabetes mellitus. Diabetes Mellitus. 2016;19(1):89-96. (In Russ.). doi: https://doi.org/10.14341/DM7233

17. Chernikova NA, Ametov AS. Experience of using the Russian dipeptidyl peptidase 4 inhibitor Gosogliptin. Results of the ONYX study. ENDOCRINOLOGY. News, Opinions, Training. 2021;10(1):62-69. (In Russ.). doi: https://doi.org/10.33029/2304-9529-2021-10-1-62-69

18. Nelson KM, Reiber G, Boyko EJ. Diet and Exercise Among Adults With Type 2 Diabetes: Findings from the Third National Health and Nutrition Examination Survey (NHANES III). Diabetes Care. 2002;25(10):1722–1728. doi: https://doi.org/10.2337/diacare.25.10.1722

19. Katsaridis S, Grammatikopoulou MG, Gkiouras K, et al. Low Reported Adherence to the 2019 American Diabetes Association Nutrition Recommendations among Patients with Type 2 Diabetes Mellitus, Indicating the Need for Improved Nutrition Education and Diet Care. Nutrients. 2020;12(11):3516. doi: https://doi.org/10.3390/nu12113516

20. ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, American Diabetes Association, et al. 9. Pharmacologic approaches to glycemic treatment: Standards of Care in Diabetes-2023. Diabetes Care. 2023;46(Suppl 1):S140–57. doi: https://doi.org/10.2337/dc23-S009

21. Suprapti B, Izzah Z, Anjan AG. Prevalence of medication adherence and glycemic control among patients with type 2 diabetes and influencing factors: A cross-sectional study. Glob Epidemiol. 2023;5:100113. doi: https://doi.org/10.1016/j.gloepi.202

22. Bramante CT, Lee JC, Gudzune KA. Treatment of Obesity in Patients With Diabetes. Diabetes Spectr. 2017;30(4):237–243. doi: https://doi.org/10.2337/ds17-0030

23. Lingvay I, Sumithran P, Cohen R, et al Obesity management as a primary treatment goal for type 2 diabetes: time to reframe the conversation. Lancet (London England). 2022;399(10322):394–405. doi: https://doi.org/10.1016/S0140-6736(21)01919-X

24. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24):2560–2572. doi: https://doi.org/10.1056/NEJMoa0802987

25. Diabetes and cardiovascular disease: Epidemiology, biological mechanisms, treatment recommendations and future research. World J Diabetes. 2015;6(13):1246–1258. doi: https://doi.org/10.4239/wjd.v6.i13.1246

26. Khdour M, Awadallah HB, Al-Hamed Dua’a H. Assessment of treatment satisfaction and adherence amongst diabetic patients in governmental primary care clinic of Ramallah, West-Bank. Hosp Pract. 2021;49(1):27-33. doi: https://doi.org/10.1080/21548331.2020.1822083