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

BACKGROUND: 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. METHODS: This post hoc analysis of the LAMP trial (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. RESULTS: 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%]; NNT=8) and vascular events (5.8% versus 19.2%; absolute risk reduction, 13.4% [95% CI, 6.6%–20.2%]; NNT=8). No significant benefit was observed in those with homeostasis model assessment of IR <2.5. CONCLUSIONS: 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. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03948347.