Type 2 diabetes mellitus is one of the most common chronic diseases worldwide and one of the highest morbidity factors. Lowering the levels of Hemoglobin A1c (HbA1c) by strict glycemic control is the most important predictor of preventing complications. Insulin, one of the long-term drugs used to achieve this goal, however adherence and persistence to insulin therapy is not so high due to some barrier such fear of injections, fear of hypoglycaemia, obesity risk etc. This study designed to retrospectively evaluate change in glycemic control of patients with type 2 diabetes who had been on insulin therapy and wanted to quit or unwilling to use insulin therapy for any reason, and given oral antidiabetic combination therapy (metformin + glitazone + DPP-4 inhibitor + SGLT-2 inhibitor). A total of 76 patients met the inclusion criteria’s were retrospectively analyzed from hospital records. HbA1c, body mass index, and fasting plasma glucose levels were evaluated while using basal/bolus insulin therapy and after oral anti diabetic combination therapy. After antidiabetic combination therapy all glycemic control parameters significantly improved. 39.5% of the patients reached the glycemic target (HbA1c< 7%), and mean HbA1c level decreased 1.9%. The study suggested that metformin + glitazone + DPP-4 inhibitor + SGLT-2 inhibitor combination may be effective to maintain glycemic control in some type 2 diabetic patients who could not keep up insulin therapy and/or who developed clinical inertia.
___
1. WHO. “Diabetes Mellitus Fact Sheets.” https://www.who.int/mediacentre/factsheets/fs138/en/ access date 22.05.2019
2. DeFronzo RA. From the triumvirate to the „ominous octet”: a new paradigm for the treat-ment of type 2 diabetes mellitus. Clin Diab. 2009;10:101-28.
3. The diabetes control and complications trial research group. The effect of intensive treat-ment of diabetes onthe development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977–86
4. Group UPDS. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837-53.
5. Nakagami T, Kawahara R, Hori S, et al. Glycemic Control and Prevention of Retino-pathy in Japanese NIDDM Patients: A 10-year follow-up study. Diabetes Care. 1997;20:621-2.
6. Klein R, Klein BE, Moss SE. Relation of glycemic control to diabetic microvascular complica-tions in diabetes mellitus. Ann Intern Med. 1996;124(1_Part_2):90-6.
7. Inzucchi SE, Bergenstal RM, Buse JB, et al. Manage-ment 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). Diabetes care. 2012;35:1364-79.
8. Federation I. IDF Diabetes Atlas Eighth Edition 2017/2017.
9. Satman İ, Grubu TÇ. TURDEP-II Çalışması ilk sonuçlar, 32. TEMH Kongresi. 13-17 Ekim 2010. Antalya, Türkiye.
10. Seaquist ER, Anderson J, Childs B, et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society.J Clin Endocrinol. 2013;98:1845-59.
11. TEMD Diabetes Mellitus ve Komplikasyonlarının Tanı, Tedavi ve İzlem Kılavuzu-2018. http://www.temd.org.tr/admin/uploads/tbl_gruplar/2018051711 926-2018-05-17tbl_gruplar113924.pdf acces date:22.05.2019
12. Bailey CJ, Turner RC. Metformin. N Engl J Med. 1996;334:574-9.
13. DeFronzo RA, Goodman AM, Group MMS. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. N Engl J Med. 1995;333:541-9.
14. Knowler WC, Barrett-Connor E, Fowler SE, et al. Re-duction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393-403.
15. Yki-Järvinen H. Thiazolidinediones. N Engl J Med. 2004;351:1106-18.
16. Kahn SE, Haffner SM, Heise MA, et al. Glycemic du-rability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006;355:2427-43.
17. Home PD, Pocock SJ, Beck-Nielsen H, et al. Rosiglitazone evaluated for cardiovascular outcomes—an interim analysis. N Engl J Med. 2007;357:28-38.
18. Singh S, Loke YK, Furberg CD. Thiazolidinediones and heart failure: a teleo-analysis. Diabe-tes care. 2007;30:2148-53.
19. Mulvihill EE, Drucker DJ. Pharmacology, physiology, and mechanisms of action of dipeptidyl peptidase-4 inhibitors. Endocr Rev. 2014;35:992-1019.
20. Karagiannis T, Paschos P, Paletas K, et al. Dipeptidyl peptidase-4 inhibi-tors for treatment of type 2 diabetes mellitus in the clinical setting: systematic review and me-ta-analysis. BMJ. 2012;344:e1369.
21. Liu SC, Tu YK, Chien MN, et al. Effect of antidiabetic agents added to metformin on glycaemic control, hypoglycaemia and weight change in patients with type 2 diabetes: a network meta-analysis. Diabetes Obes Metab. 2012;14:810-20.
22. Wu D, Li L, Liu C. Efficacy and safety of dipeptidyl peptidase- 4 inhibitors and metformin as initial combination therapy and as monotherapy in patients with type 2 diabetes mellitus: a meta-analysis. Diabetes Obes Metab. 2014;16:30-7.
23. Jabbour S, Goldstein B. Sodium glucose co-transporter 2 inhibitors: blocking renal tubular reabsorption of glucose to improve glycaemic control in patients with diabetes. Int. J. Clin. Pract. 2008;62:1279-84.
24. Chao EC, Henry RR. SGLT2 inhibition—a novel strategy for diabetes treatment. Nat Rev Drug Discov. 2010;9:551.
25. Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes care. 2009;32:193-203.
26. Khunti K, Wolden ML, Thorsted BL, et al. Clinical inertia in people with type 2 diabetes: a retrospective cohort study of more than 80,000 people. Diabetes care. 2013;36:3411-7.
27. Abdul-Ghani M, Migahid O, Megahed A, et al. Combina-tion therapy with exenatide plus pioglitazone versus basal/bolus insulin in patients with poorly controlled type 2 diabetes on sulfonylurea plus metformin: the Qatar Study. Diabetes Care. 2017;40:325-31.
28. Esposito K, Chiodini P, Maiorino MI, et al. A nomog-ram to estimate the HbA1c response to different DPP-4 inhibitors in type 2 diabetes: a syste-matic review and meta-analysis of 98 trials with 24 163 patients. BMJ Open. 2015;5:e005892.
29. Tahrani AA, Barnett AH, Bailey CJ. SGLT inhibitors in management of diabetes. Lancet Diabetes Endocrinol. 2013;1:140-51.
30. Shyangdan DS, Uthman OA, Waugh N. SGLT-2 receptor inhibitors for treating patients with type 2 diabetes mellitus: a systematic review and network meta-analysis. BMJ Open. 2016;6:e009417.
31. Clar C, Royle P, Waugh N. Adding pioglitazone to insulin containing regimens in type 2 dia-betes: systematic review and meta-analysis. PLoS One. 2009;4(7):e6112.
32. Bolen S, Feldman L, Vassy J, et al. Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann In-tern Med. 2007;147:386-99.
33. Aguilar, D., Bozkurt, B., Ramasubbu, K., & Deswal, A. Relationship of hemoglobin A1C and mortality in heart failure patients with diabetes. J Am Coll Cardiol. 2009;54:422-8.