Effect of race on cardiometabolic responses to once-weekly exenatide: insights from the Exenatide Study of Cardiovascular Event Lowering (EXSCEL)

Davis, T. M. E., Giczewska, A., Lokhnygina, Y., Mentz, R. J., Sattar, N. and Holman, R. R. (2022) Effect of race on cardiometabolic responses to once-weekly exenatide: insights from the Exenatide Study of Cardiovascular Event Lowering (EXSCEL). Cardiovascular Diabetology, 21, 116. (doi: 10.1186/s12933-022-01555-z) (PMID:35761271) (PMCID:PMC9238154)

Abstract

Background: To determine whether there were racial differences in short-term cardiometabolic responses to once-weekly exenatide (EQW) in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL). Methods: EXSCEL enrolled 14,752 patients with type 2 diabetes (hemoglobin A1c (HbA1c) 6.5–10.0% [48–86 mmol/mol]) with or without cardiovascular disease who were randomized double-blind to EQW or placebo. Background glucose-lowering/other cardiovascular therapies were unaltered for 6 months post-randomization unless clinically essential, facilitating comparison of EQW-associated effects in 14,665 evaluable participants self-identifying as White (n = 11,113), Asian (n = 1444), Black (n = 870), or Other Race (n = 1,238. Placebo-adjusted 6 month absolute changes in cardiometabolic variables were assessed using generalized linear models. Results: Mean 6-month placebo-adjusted HbA1c reductions were similar in the four groups (range 0.54–0.67% [5.9 to 7.3 mmol/mol], P = 0.11 for race×treatment interaction), with no significant difference in Asians (reference) versus other groups after covariate adjustment (all P ≥ 0.10). Six-month placebo-adjusted mean changes in systolic (−1.8 to 0.0 mmHg) and diastolic (0.2 to 1.2 mmHg) blood pressure, serum LDL (− 0.06 to 0.02 mmol/L) and HDL (0.00 to 0.01 mmol/L) cholesterol, and serum triglycerides (−0.1 to 0.0 mmol/L) were similar in the racial groups (P ≥ 0.19 for race×treatment interaction and all P ≥ 0.13 for comparisons of Asians with other races). Resting pulse rate increased more in Asians (4 beats/min) than in other groups (≤ 3 beats/min, P = 0.016 for race×treatment interaction and all P ≤ 0.050 for comparisons of Asians with other races). Conclusions: Short-term cardiometabolic responses to EQW were similar in the main racial groups in EXSCEL, apart from a greater pulse rate increase in Asians. Trial registration: https://clinicaltrials.gov NCT01144338.

• Item Type: Articles
• Additional Information: EXSCEL was sponsored and funded by Amylin Pharmaceuticals (San Diego, CA), a wholly owned subsidiary of AstraZeneca (Gaithersburg, MD).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Sattar, Professor Naveed
• Authors: Davis, T. M. E., Giczewska, A., Lokhnygina, Y., Mentz, R. J., Sattar, N., and Holman, R. R.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Cardiovascular Diabetology
• Publisher: BioMed Central
• ISSN: 1475-2840
• ISSN (Online): 1475-2840
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Cardiovascular Diabetology 21: 116
• Publisher Policy: Reproduced under a Creative Commons License