344
Views
1
CrossRef citations to date
0
Altmetric
CLINICAL TRIAL REPORT

Impact of Fixed Combination of Metformin and Pioglitazone on Insulin Resistance of Patients with Type 2 Diabetes: Results of a Randomized Open-Label Study

, , , , &
Pages 2911-2919 | Received 29 May 2023, Accepted 29 Aug 2023, Published online: 20 Sep 2023

References

  • Tinajero MG, Malik VS. An update on the epidemiology of type 2 diabetes: a global perspective. Endocrinol Metab Clin North Am. 2021;50(3):337–355. doi:10.1016/j.ecl.2021.05.013
  • Pearson ER. Type 2 diabetes: a multifaceted disease. Diabetologia. 2019;62(7):1107–1112. doi:10.1007/s00125-019-4909-y
  • Yaribeygi H, Farrokhi FR, Butler AE, et al. Insulin resistance: review of the underlying molecular mechanisms. J Cell Physiol. 2019;234(6):8152–8161. doi:10.1002/jcp.27603
  • Ndisang JF, Vannacci A, Rastogi S. Insulin resistance, type 1 and type 2 diabetes, and related complications 2017. J Diabetes Res. 2017;2017:1478294. doi:10.1155/2017/1478294
  • Kostov K. Effects of magnesium deficiency on mechanisms of insulin resistance in type 2 diabetes: focusing on the processes of insulin secretion and signaling. Int J Mol Sci. 2019;20(6):1351. doi:10.3390/ijms20061351
  • Laakso M. Biomarkers for type 2 diabetes. Mol Metab. 2019;27(Suppl 2):S139–s146. doi:10.1016/j.molmet.2019.06.016
  • Tanase DM, Gosav EM, Costea CF, et al. The intricate relationship between Type 2 Diabetes Mellitus (T2DM), Insulin Resistance (IR), and Nonalcoholic Fatty Liver Disease (NAFLD). J Diabetes Res. 2020;2020:3920196. doi:10.1155/2020/3920196
  • Nauck MA, Wefers J, Meier JJ. Treatment of type 2 diabetes: challenges, hopes, and anticipated successes. Lancet Diabetes Endocrinol. 2021;9(8):525–544. doi:10.1016/S2213-8587(21)00113-3
  • Mastrototaro L, Roden M. Insulin resistance and insulin sensitizing agents. Metabolism. 2021;125:154892. doi:10.1016/j.metabol.2021.154892
  • Eguchi K, Tomizawa H, Ishikawa J, et al. Comparison of the effects of pioglitazone and metformin on insulin resistance and hormonal markers in patients with impaired glucose tolerance and early diabetes. Hypertens Res. 2007;30(1):23–30. doi:10.1291/hypres.30.23
  • Natali A, Ferrannini E. Effects of metformin and thiazolidinediones on suppression of hepatic glucose production and stimulation of glucose uptake in type 2 diabetes: a systematic review. Diabetologia. 2006;49(3):434–441. doi:10.1007/s00125-006-0141-7
  • Inzucchi SE, Viscoli CM, Young LH, et al. Pioglitazone prevents diabetes in patients with insulin resistance and cerebrovascular disease. Diabetes Care. 2016;39(10):1684–1692. doi:10.2337/dc16-0798
  • Perez A, Zhao Z, Jacks R, et al. Efficacy and safety of pioglitazone/metformin fixed-dose combination therapy compared with pioglitazone and metformin monotherapy in treating patients with T2DM. Curr Med Res Opin. 2009;25(12):2915–2923. doi:10.1185/03007990903350011
  • Ferrannini G, Hach T, Crowe S, et al. Energy balance after sodium-glucose cotransporter 2 inhibition. Diabetes Care. 2015;38(9):1730–1735. doi:10.2337/dc15-0355
  • Ruud J, Steculorum SM, Brüning JC. Neuronal control of peripheral insulin sensitivity and glucose metabolism. Nat Commun. 2017;8(1):15259. doi:10.1038/ncomms15259
  • Kullmann S, Hummel J, Wagner R, et al. empagliflozin improves insulin sensitivity of the hypothalamus in humans with prediabetes: a randomized, double-blind, placebo-controlled, Phase 2 trial. Diabetes Care. 2022;45(2):398–406. doi:10.2337/dc21-1136
  • Nunez Lopez YO, Retnakaran R, Zinman B, et al. Predicting and understanding the response to short-term intensive insulin therapy in people with early type 2 diabetes. Mol Metab. 2019;20:63–78. doi:10.1016/j.molmet.2018.11.003
  • Baldi S, Bonnet F, Laville M, et al. Influence of apolipoproteins on the association between lipids and insulin sensitivity: a cross-sectional analysis of the RISC study. Diabetes Care. 2013;36(12):4125–4131. doi:10.2337/dc13-0682
  • Yang L, Liang H, Liu X, et al. Islet function and insulin sensitivity in latent autoimmune diabetes in adults taking sitagliptin: a randomized trial. J Clin Endocrinol Metab. 2021;106(4):e1529–e1541. doi:10.1210/clinem/dgab026
  • Luukkonen PK, Zhou Y, Sädevirta S, et al. Hepatic ceramides dissociate steatosis and insulin resistance in patients with non-alcoholic fatty liver disease. J Hepatol. 2016;64(5):1167–1175. doi:10.1016/j.jhep.2016.01.002
  • Lee SH, Park SY, Choi CS. Insulin resistance: from mechanisms to therapeutic strategies. Diabetes Metab J. 2022;46(1):15–37. doi:10.4093/dmj.2021.0280
  • Shigiyama F, Kumashiro N, Miyagi M, et al. Effectiveness of dapagliflozin on vascular endothelial function and glycemic control in patients with early-stage type 2 diabetes mellitus: DEFENCE study. Cardiovasc Diabetol. 2017;16(1):84. doi:10.1186/s12933-017-0564-0
  • Hanefeld M, Pfützner A, Forst T, et al. Double-blind, randomized, multicentre, and active comparator controlled investigation of the effect of pioglitazone, metformin, and the combination of both on cardiovascular risk in patients with type 2 diabetes receiving stable basal insulin therapy: the PIOCOMB study. Cardiovasc Diabetol. 2011;10:65. doi:10.1186/1475-2840-10-65
  • Kaku K. Efficacy and safety of therapy with metformin plus pioglitazone in the treatment of patients with type 2 diabetes: a double-blind, placebo-controlled, clinical trial. Curr Med Res Opin. 2009;25(5):1111–1119. doi:10.1185/03007990902820816
  • Elkind-Hirsch KE, Seidemann E, Harris R. A randomized trial of dapagliflozin and metformin, alone and combined, in overweight women after gestational diabetes mellitus. Am J Obstet Gynecol MFM. 2020;2(3):100139. doi:10.1016/j.ajogmf.2020.100139
  • Wang Y, Hu X, Liu X, et al. An overview of the effect of sodium glucose cotransporter 2 inhibitor monotherapy on glycemic and other clinical laboratory parameters in type 2 diabetes patients. Ther Clin Risk Manag. 2016;12:1113–1131. doi:10.2147/TCRM.S112236
  • Scheen AJ. Cardiovascular effects of new oral glucose-lowering agents: DPP-4 and SGLT-2 Inhibitors. Circ Res. 2018;122(10):1439–1459. doi:10.1161/CIRCRESAHA.117.311588
  • Heerspink HJ, Perkins BA, Fitchett DH, et al. Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus: cardiovascular and kidney effects, potential mechanisms, and clinical applications. Circulation. 2016;134(10):752–772. doi:10.1161/CIRCULATIONAHA.116.021887
  • El-Sayed N, Mostafa YM, AboGresha NM, et al. Dapagliflozin attenuates diabetic cardiomyopathy through erythropoietin up-regulation of AKT/JAK/MAPK pathways in streptozotocin-induced diabetic rats. Chem Biol Interact. 2021;347:109617. doi:10.1016/j.cbi.2021.109617
  • Joannides CN, Mangiafico SP, Waters MF, et al. Dapagliflozin improves insulin resistance and glucose intolerance in a novel transgenic rat model of chronic glucose overproduction and glucose toxicity. Diabetes Obes Metab. 2017;19(8):1135–1146. doi:10.1111/dom.12923
  • Tsai KF, Chen Y-L, Chiou TT-Y, et al. Emergence of SGLT2 inhibitors as powerful antioxidants in human diseases. Antioxidants. 2021;10(8):1166. doi:10.3390/antiox10081166
  • Zhang E, Zhao Y, Hu H. Impact of sodium glucose cotransporter 2 inhibitors on nonalcoholic fatty liver disease complicated by diabetes mellitus. Hepatol Commun. 2021;5(5):736–748. doi:10.1002/hep4.1611
  • Han T, Fan Y, Gao J, et al. Sodium glucose cotransporter 2 inhibitor dapagliflozin depressed adiposity and ameliorated hepatic steatosis in high-fat diet induced obese mice. Adipocyte. 2021;10(1):446–455. doi:10.1080/21623945.2021.1979277
  • DeFronzo RA, Inzucchi S, Abdul-Ghani M, et al. Pioglitazone: the forgotten, cost-effective cardioprotective drug for type 2 diabetes. Diab Vasc Dis Res. 2019;16(2):133–143. doi:10.1177/1479164118825376
  • Lewis JD, Habel LA, Quesenberry CP, et al. Pioglitazone use and risk of bladder cancer and other common cancers in persons with diabetes. JAMA. 2015;314(3):265–277. doi:10.1001/jama.2015.7996
  • Einhorn D, Fonseca V. Revisiting the use of Pioglitazone in the treatment of type 2 diabetes. Endocr Pract. 2016;22(11):1343–1346. doi:10.4158/EP161409.CO
  • Ipsen E, Madsen KS, Chi Y, et al. Pioglitazone for prevention or delay of type 2 diabetes mellitus and its associated complications in people at risk for the development of type 2 diabetes mellitus. Cochrane Database Syst Rev. 2020;11(11):Cd013516. doi:10.1002/14651858.CD013516.pub2
  • Della Pepa G, Russo M, Vitale M, et al. Pioglitazone even at low dosage improves NAFLD in type 2 diabetes: clinical and pathophysiological insights from a subgroup of the TOSCA.IT randomised trial. Diabetes Res Clin Pract. 2021;178:108984. doi:10.1016/j.diabres.2021.108984
  • Nesti L, Tricò D, Mengozzi A, et al. Rethinking pioglitazone as a cardioprotective agent: a new perspective on an overlooked drug. Cardiovasc Diabetol. 2021;20(1):109. doi:10.1186/s12933-021-01294-7
  • Lee M, Saver JL, Liao H-W, et al. Pioglitazone for secondary stroke prevention: a systematic review and meta-analysis. Stroke. 2017;48(2):388–393. doi:10.1161/STROKEAHA.116.013977
  • Flory J, Lipska K. Metformin in 2019. JAMA. 2019;321(19):1926–1927. doi:10.1001/jama.2019.3805
  • Zhang K, Yang W, Dai H, et al. Cardiovascular risk following metformin treatment in patients with type 2 diabetes mellitus: results from meta-analysis. Diabetes Res Clin Pract. 2020;160:108001. doi:10.1016/j.diabres.2020.108001
  • Han Y, Xie H, Liu Y, et al. Effect of metformin on all-cause and cardiovascular mortality in patients with coronary artery diseases: a systematic review and an updated meta-analysis. Cardiovasc Diabetol. 2019;18(1):96. doi:10.1186/s12933-019-0900-7
  • Li T, Providencia R, Mu N, et al. Association of metformin monotherapy or combined therapy with cardiovascular risks in patients with type 2 diabetes mellitus. Cardiovasc Diabetol. 2021;20(1):30. doi:10.1186/s12933-020-01202-5
  • Bromage DI, Godec TR, Pujades-Rodriguez M, et al. Metformin use and cardiovascular outcomes after acute myocardial infarction in patients with type 2 diabetes: a cohort study. Cardiovasc Diabetol. 2019;18(1):168. doi:10.1186/s12933-019-0972-4
  • Griffin SJ, Leaver JK, Irving GJ. Impact of metformin on cardiovascular disease: a meta-analysis of randomised trials among people with type 2 diabetes. Diabetologia. 2017;60(9):1620–1629. doi:10.1007/s00125-017-4337-9
  • Lamanna C, Monami M, Marchionni N, et al. Effect of metformin on cardiovascular events and mortality: a meta-analysis of randomized clinical trials. Diabetes Obes Metab. 2011;13(3):221–228. doi:10.1111/j.1463-1326.2010.01349.x
  • Seufert J. A fixed-dose combination of pioglitazone and metformin: a promising alternative in metabolic control. Curr Med Res Opin. 2006;22(Suppl 2):S39–48. doi:10.1185/030079906X121002
  • Šebeková K, Gurecká R, Csongová M, et al. Lean insulin-resistant young adults display increased cardiometabolic risk: a retrospective cross-sectional study. Diabetes Res Clin Pract. 2022;185:109217. doi:10.1016/j.diabres.2022.109217
  • Derosa G, Maffioli P. Thiazolidinediones plus metformin association on body weight in patients with type 2 diabetes. Diabetes Res Clin Pract. 2011;91(3):265–270. doi:10.1016/j.diabres.2010.08.001
  • Derosa G, Tinelli C, Maffioli P. Effects of pioglitazone and rosiglitazone combined with metformin on body weight in people with diabetes. Diabetes Obes Metab. 2009;11(12):1091–1099. doi:10.1111/j.1463-1326.2009.01087.x
  • Rosenstock J, Vico M, Wei L, et al. Effects of dapagliflozin, an SGLT2 inhibitor, on HbA(1c), body weight, and hypoglycemia risk in patients with type 2 diabetes inadequately controlled on pioglitazone monotherapy. Diabetes Care. 2012;35(7):1473–1478. doi:10.2337/dc11-1693
  • Rossetti L, Giaccari A, DeFronzo RA. Glucose toxicity. Diabetes Care. 1990;13(6):610–630. doi:10.2337/diacare.13.6.610
  • Luo W, Ai L, Wang B-F, et al. High glucose inhibits myogenesis and induces insulin resistance by down-regulating AKT signaling. Biomed Pharmacother. 2019;120:109498. doi:10.1016/j.biopha.2019.109498