Pioglitazone/Exenatide/SGLT-2 inhibitor combination therapy versus insulin therapy in patients with poorly controlled type 2 diabetes

Year 2024, , 121 - 126, 08.03.2024

Hakan Düğer , Bekir Ucan

https://doi.org/10.38053/acmj.1415215

Abstract

Aims: We aimed to investigate the changes in glycemic status and beta cell function in type 2 diabetes mellitus (T2DM) patients with poor glycemic control despite receiving basal/bolus insulin therapy when switched from insulin therapy to combination therapy [exenatide/pioglitazone/sodium glucose cotransporter 2 inhibitor (SGLT-2i)].
Methods: A retrospective examination was made of the data of 64 patients, aged >18 years, diagnosed with T2DM, who were being followed up in the endocrinology outpatient clinic and were switched from basal/bolus insulin therapy to triple combination therapy. At the time of the patients changing to combination therapy, the glycosylated hemoglobin (HbA1c) value was ≥8.5% and fasting c peptide value was within the normal reference range. The anthropometric data of the patients, and glycemic and biochemistry values with modified homeostastis model assessment β (HOMA-β) levels were compared before the combination therapy and at 6 months after.
Results: Compared to the baseline values, a decrease was seen after 6 months in the values of body weight (89.6±5.8 vs. 83.8±3.6, p=0.015), body mass index (BMI) (38.3±2.7 vs. 33.5±1.9, p=0.011), and waist circumference (105.6±8.8 vs. 99.7±6, p=0.027). A decrease was determined in fasting blood glucose (FBG) (197±27.3 vs. 129±13.1, p<0.01) and HbA1c (9.8±1.6 vs. 8.1±1.1, p<0.01) values, and an increase in the HOMA-β value [233 (187.5, 282.3) vs. 318 (272.1, 365.2), p<0.001].
Conclusion: T2DM is a complex metabolic disease with more than one disorder in the pathogenesis, so it is difficult to control the disease in the long term with a single drug class. The use of drugs in a combined form, which will allow weight loss, have a positive effect on insulin resistance and improve beta cell function, without causing hypoglycemia, can achieve a better and sustainable glycemic and metabolic status.

Keywords

Diabetes mellitus, exenatide, piogitazone, SGLT-2

References

• Kanat M, DeFronzo RA, Abdul-Ghani MA. Treatment of prediabetes. World J Diabetes. 2015;25(12):1207-1222. doi: 10.4239/wjd.v6.i12.1207
• Leahy JL. Natural history of beta-cell dysfunction in NIDDM. Diabetes Care. 1990;13(9):992-1010. doi: 10.2337/diacare.13.9.992
• Kaiser N, Leibowitz G, Nesher R. Glucotoxicity and beta-cell failure in type 2 diabetes mellitus. J Pediatr Endocrinol Metab. 2003;16(1):5-22. doi: 10.1515/jpem.2003.16.1.5
• Marchetti P, Dotta F, Lauro D, Purrello F. An overview of pancreatic beta-cell defects in human type 2 diabetes: implications for treatment. Regul Pept. 2008;146(1-3):4-11. doi: 10.1016/j.regpep.2007.08.017
• Davies MJ, Aroda VR, Collins BS, et al. Management of hyperglycemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2022;45(11):2753-2786. doi: 10.2337/dci22-0034
• 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. Diabetes Care. 2013;36(5):1384-1395. doi: 10.2337/dc12-2480
• Del Prato S, Marchetti P. Targeting insulin resistance and beta-cell dysfunction: the role of thiazolidinediones. Diabetes Technol Ther. 2004;6(5):719-731. doi: 10.1089/dia.2004.6.719
• Ovalle F, Bell DS. Effect of rosiglitazone versus insulin on the pancreatic beta-cell function of subjects with type 2 diabetes. Diabetes Care. 2004;27(11):2585-2589. doi: 10.2337/diacare.27.11.2585
• Gastaldelli A, Ferrannini E, Miyazaki Y, Matsuda M, Mari A, DeFronzo RA. Thiazolidinediones improve beta-cell function in type 2 diabetic patients. Am J Physiol Endocrinol Metab. 2007;292(3):E871-E883. doi: 10.1152/ajpendo.00551.2006
• Buteau J, El-Assaad W, Rhodes CJ, Rosenberg L, Joly E, Prentki M. Glucagon-like peptide-1 prevents beta cell glucolipotoxicity. Diabetologia. 2004;47(5):806-815. doi: 10.1007/s00125-004-1379-1386
• Abdul-Ghani MA, Norton L, Defronzo RA. Role of sodium-glucose cotransporter 2 (SGLT 2) inhibitors in the treatment of type 2 diabetes. Endocr Rev. 2011;32(4):515-531. doi: 10.1210/er.2010-0029
• Katz PM, Leiter LA. The role of the kidney and SGLT2 inhibitors in type 2 diabetes. Can J Diabetes. 2015;39(5):167-175. doi: 10.1016/j.jcjd.2015.09.001
• Li X, Zhou ZG, Qi HY, Chen XY, Huang G. Replacement of insulin by fasting C-peptide in modified homeostasis model assessment to evaluate insulin resistance and islet β cell function. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2004;29(4):419-423.
• Russell C, Petrie J. Chapter 6: GLP-1 receptor agonists. In: Fisher M, Mckay GA, Llano A, eds. Diabetes Drug Notes. John Wiley and Sons: 2022:130-160.
• Kaneto H, Matsuoka TA, Nakatani Y, et al. Oxidative stress, ER stress, and the JNK pathway in type 2 diabetes. J Mol Med. 2005;83(6):429-439. doi: 10.1007/s00109-005-0640-x
• Kanda Y, Shimoda M, Hamamoto S, et al. Molecular mechanism by which pioglitazone preserves pancreatic beta-cells in obese diabetic mice: evidence for acute and chronic actions as a PPARgamma agonist. Am J Physiol Endocrinol Metab. 2010;298(2):278-286. doi:10.1152/ajpendo.00388.2009
• Shimoda M, Kanda Y, Hamamoto S, et al. The human glucagon-like peptide-1 analogue liraglutide preserves pancreatic beta cells via regulation of cell kinetics and suppression of oxidative and endoplasmic reticulum stress in a mouse model of diabetes. Diabetologia. 2011;54(5):1098-1108. doi: 10.1007/s00125-011-2069-9
• Wang AP, Li X, Zheng Y, et al. Thiazolidinediones protect mouse pancreatic b-cells directly from cytokine-induced cytotoxicity through PPAR-dependent mechanisms. Acta Diabetol. 2013;50(2):163-173. doi: 10.1007/s00592-010-0239-8
• Marmentini C, Guimarães DSPSF, de Lima TI, et al. Rosiglitazone protects INS-1E cells from human islet amyloid polypeptide toxicity. Eur J Pharmacol. 2022;928:175122. doi: 10.1016/j.ejphar.2022.175122
• Kanno A, Asahara SI, Kawamura M, et al. Early administration of dapagliflozin preserves pancreatic b-cell mass through a legacy effect in a mouse model of type 2 diabetes. J Diabetes Investig. 2019;10(3):577-590. doi: 10.1111/jdi.12945
• Hansen HH, Jelsing J, Hansen CF, et al. The sodium glucose cotransporter type 2 inhibitor empagliflozin preserves b-cell mass and restores glucose homeostasis in the male zucker diabetic fatty rat. J Pharmacol Exp Ther. 2014;350(3):657-664. doi: 10.1124/jpet.114.213454
• Kimura T, Kaneto H, Shimoda M, et al. Protective effects of pioglitazone and/or liraglutide on pancreatic β-cells in db/db mice: Comparison of their effects between in an early and advanced stage of diabetes. Mol Cell Endocrinol. 2015;15:400:78-89. doi: 10.1016/j.mce.2014.11.018
• Abd El Aziz MS, Kahle M, Meier JJ, Nauck MA. A meta-analysis comparing clinical effects of short- or long-acting GLP-1 receptor agonists versus insulin treatment from head-to-head studies in type 2 diabetic patients. Diabetes Obes Metab. 2017;19(2):216-227. doi: 10.1111/dom.12804
• Nauck MA, Quast DR, Wefers J, Meier JJ. GLP-1 receptor agonists in the treatment of type 2 diabetes-state-of-the-art. Mol Metab. 2021;46:101102. doi: 10.1016/j.molmet.2020.101102
• Brunzell JD, Davidson M, Furberg CD, et al. American Diabetes Association; American College of Cardiology Foundation. Lipoprotein management in patients with cardiometabolic risk: consensus statement from the American Diabetes Association and the American College of Cardiology Foundation. Diabetes Care. 2008;31(4):811-822. doi: 10.2337/dc08-9018
• Betteridge DJ. Effects of pioglitazone on lipid and lipoprotein metabolism. Diabetes Obes Metab. 2007;9(5):640-647. doi: 10.1111/ j.1463-1326.2007.00715.x
• Sun F, Wu S, Wang J, et al. Effect of glucagon-like peptide-1 receptor agonists on lipid profiles among type 2 diabetes: a systematic review and network meta-analysis. Clin Ther. 2015;37(1):225-241. doi: 10.1016/j.clinthera.2014.11.008
• Sánchez-García A, Simental-Mendía M, Millán-Alanís JM, Simental-Mendía LE. Effect of sodium-glucose co-transporter 2 inhibitors on lipid profile: a systematic review and meta-analysis of 48 randomized controlled trials. Pharmacol Res. 2020;160:105068. doi: 10.1016/j.phrs.2020.105068
• Baker WL, Smyth LR, Riche DM, Bourret EM, Chamberlin KW, White WB. Efects of sodium-glucose co-transporter 2 inhibitors on blood pressure: a systematic review and meta-analysis. J Am Soc Hypertens. 2014;8(4):262-275. doi: 10.1016/j.jash.2014.01.007
• Wanner C, Inzucchi SE, Lachin JM, et al. Empaglifozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375(4):323-334.
• Muskiet MHA, Tonneijck L, Smits MM, et al. GLP-1 and the kidney: from physiology to pharmacology and outcomes in diabetes. Nat Rev Nephrol. 2017;13(10):605-628.
• Van Ruiten CC, Smits MM, Kok MD, et al. Mechanisms underlying the blood pressure lowering effects of dapagliflozin, exenatide, and their combination in people with type 2 diabetes: a secondary analysis of a randomized trial. Cardiovasc Diabetol. 2022;21(1):63. doi: 10.1186/s12933-022-01492-x