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Effects of Tirzepatide vs Semaglutide on β-Cell Function, Insulin Sensitivity, and Glucose Control During a Meal Test
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Effects of Tirzepatide vs Semaglutide on β-Cell Function, Insulin Sensitivity, and Glucose Control During a Meal Test
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Journal Article
Effects of Tirzepatide vs Semaglutide on β-Cell Function, Insulin Sensitivity, and Glucose Control During a Meal Test
2024
Overview
Abstract
Context
In a clinical study, tirzepatide, a glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist (GIP/GLP-1RA), provided superior glycemic control vs the GLP-1RA semaglutide. The physiologic mechanisms are incompletely understood.
Objective
This work aimed to evaluate treatment effects by model-based analyses of mixed-meal tolerance test (MMTT) data.
Methods
A 28-week double–blind, randomized, placebo-controlled trial of patients with type 2 diabetes treated with metformin was conducted at 2 clinical research centers in Germany. Interventions included tirzepatide 15 mg, semaglutide 1 mg, and placebo. Main outcome measures included glycemic control, model-derived β-cell function indices including insulin secretion rate (ISR) at 7.2–mmol/L glucose (ISR7.2), β-cell glucose sensitivity (β-CGS), insulin sensitivity, and estimated hepatic insulin-to-glucagon ratio.
Results
Tirzepatide significantly reduced fasting glucose and MMTT total glucose area under the curve (AUC) vs semaglutide (P < .01). Incremental glucose AUC did not differ significantly between treatments; therefore, greater total glucose AUC reduction with tirzepatide was mainly attributable to greater suppression of fasting glucose. A greater reduction in total ISR AUC was achieved with tirzepatide vs semaglutide (P < .01), in the context of greater improvement in insulin sensitivity with tirzepatide (P < .01). ISR7.2 was significantly increased with tirzepatide vs semaglutide (P < .05), showing improved β-CGS. MMTT-derived β-CGS was increased but not significantly different between treatments. Both treatments reduced fasting glucagon and total glucagon AUC, with glucagon AUC significantly reduced with tirzepatide vs semaglutide (P < .01). The estimated hepatic insulin-to-glucagon ratio did not change substantially with either treatment.
Conclusion
These results suggest that the greater glycemic control observed for tirzepatide manifests as improved fasting glucose and glucose excursion control, due to improvements in ISR, insulin sensitivity, and glucagon suppression.
Publisher
Oxford University Press
Subject
/ Aged
/ Blood Glucose - drug effects
/ Diabetes mellitus (non-insulin dependent)
/ Diabetes Mellitus, Type 2 - blood
/ Diabetes Mellitus, Type 2 - drug therapy
/ Diabetes Mellitus, Type 2 - metabolism
/ Fasting
/ Female
/ Gastric Inhibitory Polypeptide
/ Glucagon
/ Glucagon-Like Peptide-2 Receptor
/ Glucagon-Like Peptides - pharmacology
/ Glucose
/ Humans
/ Hypoglycemic Agents - pharmacology
/ Hypoglycemic Agents - therapeutic use
/ Insulin
/ Insulin-Secreting Cells - drug effects
/ Insulin-Secreting Cells - metabolism
/ Liver
/ Male
/ Meals
/ Placebos
