Tirzepatide – a dual incretin agonist in the management of type 2 diabetes mellitus: a review of evidence from the SURPASS trials

Czech version

Authors: Ingrid Dravecká
Authors‘ workplace: I. interná klinika LF UPJŠ a UNLP v Košiciach
Published in: Diab Obez 2025; 25(1): 16-22
Category: Reviews

Overview

Type 2 diabetes mellitus (2TDM) is a complex chronic disease whose treatment requires targeted intervention in multiple pathophysiological mechanisms. Tirzepatide is the first representative of a new class of antidiabetic drugs – dual agonists of receptors for GLP-1 and GIP – that target multiple pathophysiological mechanisms of 2TDM. In the SURPASS clinical program (Phase 3 trial), it demonstrated consistent and significant efficacy in reducing HbA_1c levels across different patient populations. At doses of 5, 10, and 15 mg in the individual SURPASS studies, HbA_1creductions ranged from -1.87 to -2.58%, with 81–92% of patients achieving a target < 7% and up to 46% achieving normoglycemia (HbA_1c < 5.7%). Effects on body weight were also significant, with weight loss ranging from 7–13 kg, with 15–36% of patients achieving ≥ 15 % weight reduction. This effect was also present in patients treated with concomitant basal insulin, with no indication of reaching a plateau after 40–52 weeks of treatment. Tirzepatide was also associated with a beneficial effect on lipid profile (decrease in TAG, VLDL, LDL, rise in HDL) and with significant improvement in markers of insulin sensitivity and beta-cell function. The safety profile was favourable – the incidence of hypoglycemia was low and the most common adverse events were mild gastrointestinal upset. In comparison with standard treatments (semaglutide 1 mg, insulin degludec and glargine), tirzepatide demonstrated not only non-inferiority but also clinically significant superiority in most of the parameters studied. The combination of a potent glycemic effect, weight reduction, favorable lipid profile, and low risk of hypoglycemia makes tirzepatide a promising therapeutic option that may lead not only to improved metabolic compensation but also to regression of 2TDM in a selected group of patients. These findings encourage further research focused on long-term maintenance of metabolic remission and the cardiovascular benefits of dual incretin agonism.

Keywords:

Body weight – HbA1c – type 2 diabetes mellitus – hypoglycemia – dual agonists of receptors for GLP-1 and GIP – lipid profile – metabolic remission – SURPASS –tirzepatide

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