Liraglutide and Recurrent Stroke by Baseline Insulin Resistance: A Post Hoc Analysis of the LAMP Trial

Glucagon-like peptide-1 receptor agonists reduce major adverse cardiovascular events in type 2 diabetes. Although body mass index does not seem to modify these effects, whether insulin resistance influences treatment efficacy remains unclear.

This post hoc analysis of the LAMP trial (Liraglutide in Acute Minor Ischemic Stroke or High-Risk Transient Ischemic Attack Patients With Type 2 Diabetes Mellitus; a multicenter, open-label, randomized controlled trial conducted at 27 hospitals in China between June 25, 2019, and December 27, 2023) included patients with minor ischemic stroke or high-risk transient ischemic attack and type 2 diabetes. Participants were randomized (1:1) to liraglutide plus standard therapy or standard therapy alone. IR was assessed using the homeostasis model assessment of IR, with a cutoff of 2.5 based on prior studies in Asian populations. Treatment-by-IR interactions were evaluated using Cox models. Absolute risk reduction was calculated as the difference in event rates between groups and was based on crude estimates.

Among 636 enrolled patients, 510 were included in this analysis (mean age, 65 years; 64.7% male; follow-up, 3 months). A significant interaction between treatment and insulin resistance was observed for both stroke recurrence and composite vascular events (P for interaction=0.02 for both). Among patients with homeostasis model assessment of IR ≥2.5, liraglutide reduced stroke recurrence (5.8% versus 18.1%; absolute risk reduction, 12.3% [95% CI, 5.6%-19.0%]; number needed to treat=8) and vascular events (5.8% versus 19.2%; absolute risk reduction, 13.4% [95% CI, 6.6%-20.2%]; number needed to treat=8). No significant benefit was observed in those with homeostasis model assessment of IR <2.5.

IR may be an important determinant of the therapeutic efficacy of liraglutide in patients with acute minor ischemic stroke or high-risk transient ischemic attack and type 2 diabetes. IR-based stratification may help optimize the use of glucagon-like peptide-1 receptor agonists in secondary stroke prevention and guide personalized vascular risk management.

URL: https://www.clinicaltrials.gov; Unique identifier: NCT03948347.