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Título

Effect of tirzepatide on weight reduction in people with obstructive sleep apnea and obesity: a post hoc analysis of the SURMOUNT trials

Resumo

Rationale: Excess adiposity is one of the strongest risk factors for the development and progression of obstructive sleep apnea (OSA). Tirzepatide (TZP), a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, demonstrated robust weight reduction in people with obesity or overweight in the global SURMOUNT trials. This post-hoc analysis explored the effect of TZP vs placebo (PBO) on weight reduction in participants with OSA and obesity or overweight (BMI ≥27 kg/m2) in the phase 3, double-blind, PBO-controlled SURMOUNT trials.
Methods: In SURMOUNT-1 and -2, randomization occurred after the screening period. SURMOUNT-3 included a 12-week (wk) lead-in on intensive lifestyle intervention followed by randomization of participants achieving ≥5% weight reduction. In SURMOUNT-4, randomization occurred after a 36-wk lead-in on open-label TZP treatment, with a mean weight reduction of 20.9%. For the current post-hoc analysis, the analysis period was from randomization to primary endpoint i.e., wk 0 to 72 for SURMOUNT-1 to SURMOUNT-3 and wk 36 to 88 for SURMOUNT-4. Data from all randomized participants with an established OSA diagnosis at baseline who were on treatment (efficacy analysis set), received at least one dose of study drug, and had a baseline and at least one post-baseline weight measurement, were included. TZP doses were either pooled for the analysis (SURMOUNT-1 and -2) or the maximum tolerated dose (SURMOUNT-3 and -4). Percent change in body weight (BW) from randomization to endpoint, changes in cardiometabolic parameters, and the proportion of participants achieving ≥10% weight reduction at endpoint were summarized descriptively.
Results: Across trials, mean age at randomization was 51.1 to 56.8 years, BW was 111.4 to 117.0 kg in SURMOUNT-1 to SURMOUNT-3 and 95.4 kg in SURMOUNT-4, and BMI was 37.7 to 40.4 kg/m2 in SURMOUNT-1 to SURMOUNT-3 and 33.0 kg/m2 in SURMOUNT-4. TZP-treated participants were observed to have greater weight reduction than PBO (Fig 1A) and improvements in cardiometabolic parameters. More TZP-treated participants achieved ≥10% weight reduction vs PBO (Fig 1B).
Conclusions: Across the SURMOUNT trials, in participants with OSA and obesity or overweight, TZP vs PBO treatment resulted in greater, clinically meaningful, BW reduction. The ongoing SURMOUNT-OSA trial will provide further insight into the safety and efficacy of TZP treatment in OSA.

Disclosure: Originally accepted at 2024 ATS.

Palavras Chave

Tirzepatide; sleep apnea; obesity

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