COMPARISON OF EFFICACY AND SAFETY PROFILE OF EMPAGLIFLOZIN AS A COMBINATION THERAPY IN OBESE TYPE 2 DIABETIC PATIENTS
AbstractBackground: Type 2 diabetes mellitus (T2DM) is a progressive disease due to multiple pathophysiological defects. Monotherapy alone cannot achieve adequate glycemic control and can lead to treatment failure. Empagliflozin, a sodium-glucose cotransporter2 (SGLT2) inhibitor improves glycemic control in patients with T2DM. There were limited studies to determine efficacy and safety profile of empagliflozin with conventional oral antidiabetic drugs (OADs) in Pakistan. So we investigated the efficacy and safety profile of empagliflozin as add-on therapy to metformin and sitagliptin in T2DM patients. Methods: In this comparative randomized placebo-controlled trial, 240 obese type 2 diabetic patients with inadequate glycaemic control (i.e, HbA1c ≥7%) with metformin and sitagliptin were allocated in to two groups. Patients in group B were given tab empagliflozin 10mg twice a day while patients in group A were given tab placebo for a period of 24 weeks. Changes in body weight, HbA1c, blood pressure were analysed pre and post treatment by using SPSS v23. Results: Empagliflozin caused a significant reduction in body weight -6.9±2.4 kg as compared to placebo -3.1±0.8 kg with p-value <0.001. This body weight reduction was further accompanied by reduction in systolic blood pressure -10.1±2.6 mmHg in empagliflozin group versus -5.3±2.5 mmHg in placebo group with p-value <0.001, and HbA1c -1.68±0.45 in empagliflozin group versus -0.1±0.06 in placebo group with p-value <0.001. There were 28.3% patients in empagliflozin group in whom HbA1c levels reduced <7% as compared to only 13.3% patients in placebo group (p-value 0.04). However no significant adverse effects were recorded in both study groups. Conclusion: Empagliflozin as a combination therapy has good efficacy and safety profile in obese type 2 diabetic patients.
Milder T, Stocker S, Abdel Shaheed C, McGrath-Cadell L, Samocha-Bonet D, Greenfield J, et al. Combination therapy with an SGLT2 inhibitor as initial treatment for type 2 diabetes: a systematic review and meta-analysis. J Clinl Med 2019;8(1):45.
Gregg EW, Li Y, Wang J, Rios Burrows N, Ali MK, Rolka D, et al. Changes in diabetes-related complications in the United States, 1990–2010. N Engl J Med 2014;370(16):1514–23.
Lind M, Garcia-Rodriguez LA, Booth GL, Cea-Soriano L, Shah BR, Ekeroth G, et al. Mortality trends in patients with and without diabetes in Ontario, Canada and the UK from 1996 to 2009: a population-based study. Diabetologia 2013;56(12):2601–8.
Fonseca VA. Defining and characterizing the progression of type 2 diabetes. Diabetes Care 2009;32(Suppl 2):S151–6.
Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, 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(1):193–203.
Davies MJ, D'Alessio DA, Fradkin J, Kernan WN, Mathieu C, Mingrone G, et al. Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018;41(12):2669–701.
Garber AJ, Abrahamson MJ, Barzilay JI, Blonde L, Bloomgarden ZT, Bush MA, et al. Consensus statement by the american association of clinical endocrinologists and american college of endocrinology on the comprehensive type 2 diabetes management algorithm - 2019 executive summary. Endocr Pract 2019;25(1):69–100.
Cersosimo E, Johnson EL, Chovanes C, Skolnik N. Initiating therapy in patients newly diagnosed with type 2 diabetes: Combination therapy vs a stepwise approach. Diabetes Obes Metab 2018;20(3):497–507.
Cahn A, Cefalu WT. Clinical Considerations for Use of Initial Combination Therapy in Type 2 Diabetes. Diabetes Care 2016;39(Suppl 2):S137–45.
Ferrannini E. Sodium-glucose co-transporters and their inhibition: clinical physiology. Cell Metab 2017;26(1):27–38.
Wilding JP, Norwood P, T'joen C, Bastien A, List JF, Fiedorek FT. A study of dapagliflozin in patients with type 2 diabetes receiving high doses of insulin plus insulin sensitizers: applicability of a novel insulin-independent treatment. Diabetes Care 2009;32(9):1656–62.
Fujimori Y, Katsuno K, Nakashima I, Ishikawa-Takemura Y, Fujikura H, Isaji M. Remogliflozin etabonate, in a novel category of selective low-affinity sodium glucose cotransporter (SGLT2) inhibitors, exhibits antidiabetic efficacy in rodent models. J Pharmacol Exp Ther 2008;327(1):268–76.
Molugulu N, Yee LS, Ye YT, Khee TC, Nie LZ, Yee NJ, et al. Systematic review of metformin monotherapy and dual therapy with sodium glucose co-transporter 2 inhibitor (SGLT-2) in treatment of type 2 diabetes mellitus. Diabetes Res Clin Pract 2017;132:157–68.
Hadjadj S, Rosenstock J, Meinicke T, Woerle HJ, Broedl UC. Initial Combination of Empagliflozin and Metformin in Patients With Type 2 Diabetes. Diabetes Care 2016;39(10):1718–28.
Softeland E, Meier JJ, Vangen B, Toorawa R, Maldonado-Lutomirsky M, Broedl UC. Empagliflozin as Add-on Therapy in Patients With Type 2 Diabetes Inadequately Controlled With Linagliptin and Metformin: A 24-Week Randomized, Double-Blind, Parallel-Group Trial. Diabetes Care 2017;40(2):201–9.
Haring HU, Merker L, Seewaldt-Becker E, Weimer M, Meinicke T, Broedl UC, et al. Empagliflozin as add-on to metformin in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Care 2014;37(6):1650–9.
Merker L, Haring HU, Christiansen AV, Roux F, Salsali A, Kim G, et al. Empagliflozin as add-on to metformin in people with Type 2 diabetes. Diabet Med 2015;32(12):1555–67.