Tirzepatide Improved Markers of Islet Cell Function and Insulin Sensitivity in People With T2D (SURPASS-2)

• Published in: The journal of clinical endocrinology and metabolism 2024-06, Vol.109 (7), p.1745-1753
• Main Authors: Frias, Juan P, De Block, Christophe, Brown, Katelyn, Wang, Hui, Thomas, Melissa K, Zeytinoglu, Meltem, Maldonado, Juan M
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biomarkers - blood; Blood Glucose - drug effects; Blood Glucose - metabolism; Clinical; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Double-Blind Method; Female; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide-2 Receptor; Glucagon-Like Peptides - administration & dosage; Glucagon-Like Peptides - pharmacology; Glycated Hemoglobin - analysis; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - pharmacology; Hypoglycemic Agents - therapeutic use; Insulin - blood; Insulin - metabolism; Insulin Resistance; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Male; Middle Aged; Treatment Outcome
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/clinem/dgae038

In previous SURPASS studies tirzepatide reduced hemoglobin glycated A1c (HbA1c) and body weight and improved markers of insulin sensitivity and β-cell function to a greater extent than comparators. Explore changes in biomarkers of β-cell function and insulin sensitivity and in efficacy profiles in baseline biomarker quartile analyses with tirzepatide compared to semaglutide. Post hoc analysis of SURPASS-2 phase 3 trial (participants randomly assigned to receive weekly subcutaneous tirzepatide or semaglutide for 40 weeks). Post hoc analysis of 128 sites in 8 countries. A total of 1879 participants with type 2 diabetes. Once-weekly tirzepatide (5, 10, 15 mg) or semaglutide 1 mg. Change in homeostatic model assessment indices for pancreatic β-cell function (HOMA2-B) and for insulin resistance (HOMA2-IR), fasting glucagon, fasting C-peptide, and fasting insulin. At week 40, a greater increase in HOMA2-B was seen with tirzepatide (5, 10, 15 mg) doses (96.9-120.4%) than with semaglutide 1 mg (84.0%) (P < .05). There was a greater reduction in HOMA2-IR with all doses of tirzepatide (15.5%-24.0%) than with semaglutide 1 mg (5.1%) (P < .05). Tirzepatide 10 and 15 mg resulted in a significant reduction in both fasting C-peptide (5.2%-6.0%) and fasting glucagon (53.0%-55.3%) compared with an increase of C-peptide (3.3%) and a reduction of glucagon (47.7%) with semaglutide 1 mg (P < .05). HbA1c and body weight reductions were greater with all tirzepatide doses than semaglutide within each HOMA2-B and HOMA2-IR baseline quartile. In this post hoc analysis, improvements in HbA1c and weight loss were consistent and significantly higher with tirzepatide, regardless of baseline β-cell function and insulin resistance, compared with semaglutide.