Achievement of glycaemic targets with weight loss and without hypoglycaemia in type 2 diabetes with the once‐weekly glucose‐dependent insulinotropic polypeptide and glucagon‐like peptide‐1 receptor agonist tirzepatide: A post hoc analysis of the SURPASS‐1 to ‐5 studies

• Published in: Diabetes, obesity & metabolism Vol. 25; no. 4; pp. 965 - 974
• Main Authors: Lingvay, Ildiko, Cheng, Alice YY, Levine, Joshua A., Gomez‐Valderas, Elisa, Allen, Sheryl E., Ranta, Kari, Torcello‐Gómez, Amelia, Thieu, Vivian T.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2023; Wiley Subscription Services, Inc
• Subjects: Antidiabetics; Clinical trials; composite endpoint; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; Drug therapy; Gastric Inhibitory Polypeptide - therapeutic use; GIP and GLP‐1 receptor agonist; Glucagon; Glucagon-Like Peptide-1 Receptor - agonists; Glucose - therapeutic use; glycaemic control; Glycated Hemoglobin; Humans; hypoglycaemia; Hypoglycemia; Hypoglycemia - drug therapy; Hypoglycemic Agents - therapeutic use; incretin therapy; Insulin; Insulins; Placebos; tirzepatide; type 2 diabetes; Weight control; Weight Loss; composite endpoint; type 2 diabetes; hypoglycaemia; tirzepatide; weight loss; glycaemic control; incretin therapy; GIP and GLP-1 receptor agonist
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.14943

Aim To assess composite endpoints combining glycaemic control (HbA1c < 7.0%, ≤ 6.5% or < 5.7%) with weight loss (≥ 5%, ≥ 10% or ≥ 15%) and without hypoglycaemia with tirzepatide in type 2 diabetes (T2D). Materials and Methods Data from the phase 3 SURPASS programme were evaluated post hoc by trial. Participants with T2D were randomized to tirzepatide (5, 10 and 15 mg), placebo (SURPASS‐1,5), semaglutide 1 mg (SURPASS‐2) or titrated basal insulin (SURPASS‐3,4). The proportions of participants achieving the composite endpoints were compared between tirzepatide and the respective comparator groups at week 40/52. Results The proportions of participants achieving an HbA1c value of less than 7.0% with 5% or more weight loss and without hypoglycaemia ranged from 43% to 82% with tirzepatide across the SURPASS‐1 to ‐5 trials versus 4%‐5% with placebo, 51% with semaglutide 1 mg and 5% with basal insulin (P < .001 vs. all comparators). The proportions of participants achieving an HbA1c value of less than 7.0% with 10% or more, or 15% or more weight loss and without hypoglycaemia were significantly higher with all tirzepatide doses versus comparators across trials (P < .001 or P < .05). Similar results were observed for all other combinations of endpoints with an HbA1c value of 6.5% or less, or less than 5.7%, with more tirzepatide‐treated participants achieving these endpoints versus those in the comparator groups, including semaglutide. Conclusions Across the SURPASS‐1 to ‐5 clinical trials, more tirzepatide‐treated participants with T2D achieved clinically meaningful composite endpoints, which included reaching glycaemic targets with various degrees of weight loss and without hypoglycaemia, than those in the comparator groups.