Tirzepatide shows dual benefits in sleep apnea trial improving metabolism and reducing inflammation

By Hugo Francisco de SouzaReviewed by Susha Cheriyedath, M.Sc.Feb 9 2026

New clinical trial evidence suggests targeting both obesity and sleep-disordered breathing together may reshape cardiometabolic risk management in obstructive sleep apnea.

Tirzepatide on obstructive sleep apnea-related cardiometabolic risk: secondary outcomes of the SURMOUNT-OSA randomized trial. Image Credit: Mongkolchon Akesin / Shutterstock

In a recent study published in the journal Nature Medicine, researchers reported results from the SURMOUNT-OSA trial, a clinical trial evaluating the effects of tirzepatide on cardiometabolic health in adults with obesity and moderate-to-severe obstructive sleep apnea (OSA).

The study findings showed that tirzepatide significantly improved blood pressure, inflammation, and insulin resistance. Mediation analyses suggested that these benefits arose from a combination of weight loss and direct improvements in sleep-disordered breathing metrics, including the Apnea–Hypopnea Index (AHI) and sleep apnea-specific hypoxic burden. These findings highlight a potential integrated approach to OSA treatment, although longer-term clinical outcome data remain limited.

Background

OSA is a common sleep disorder characterized by repeated interruptions in breathing and has been linked to significant cardiometabolic and neurocognitive consequences.

Excess body fat is a primary reversible risk factor for OSA. However, traditional pharmacological weight-loss interventions have shown limited effectiveness, and many OSA treatments demonstrate suboptimal efficacy.

OSA treatment context

The current gold standard in OSA therapy is continuous positive airway pressure (CPAP), which uses a mask to keep the airways open during sleep. Despite its effectiveness, many patients find long-term use difficult to tolerate.

Positive airway pressure (PAP) therapy has not consistently demonstrated the cardiovascular benefits initially expected. While it addresses airway obstruction, underlying metabolic risk factors may persist, and cardiovascular outcome evidence has varied across trials.

Global obesity prevalence continues to rise, with projections indicating further increases in the coming decade. As a result, the prevalence of OSA is expected to increase, creating an urgent need for pharmacological interventions that address both obesity-related metabolic dysfunction and sleep-disordered breathing.

Study design and endpoints

This study reported secondary, OSA-specific outcomes from the SURMOUNT-OSA program. Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist evaluated for its effects on cardiometabolic health in adults.

The program consisted of two 52-week, randomized, double-blind, phase 3 clinical trials involving 469 adults with obesity and moderate-to-severe OSA. Individuals with mild OSA, diabetes, or lower body mass index ranges were excluded.

Participants were divided into two cohorts based on PAP use.

• Study 1 included participants who were unwilling or unable to use PAP therapy.
• Study 2 included participants who had used PAP successfully for at least three months and planned to continue use throughout the 52-week trial.

Participants were randomly assigned to receive a placebo or tirzepatide at the maximum tolerated dose of 10 mg or 15 mg once weekly. In addition to reducing AHI, the study assessed several secondary cardiometabolic endpoints.

1. Systolic and diastolic blood pressure were measured at week 48
2. High-sensitivity C-reactive protein (hsCRP) as a marker of systemic inflammation
3. Lipid profiles, including triglycerides and cholesterol fractions
4. Insulin sensitivity assessed using fasting insulin and the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)

Mediation analyses evaluated whether health improvements were attributable solely to weight loss or whether improvements in sleep metrics, including AHI and sleep apnea-specific hypoxic burden, contributed independently. These analyses were exploratory and not adjusted for multiple comparisons.

Key findings

Tirzepatide treatment led to broad improvements in cardiometabolic risk factors compared with placebo across both trials. Systolic blood pressure was reduced by an estimated treatment difference of −7.9 mmHg in Study 1 and −4.3 mmHg in Study 2.

Diastolic blood pressure was significantly reduced in Study 1 but not in Study 2. Mediation analyses did not identify independent effects of weight loss or OSA metrics on diastolic blood pressure.

Inflammation, as measured by hsCRP, declined substantially in both studies, as did insulin resistance, as measured by HOMA-IR. Triglyceride levels decreased by approximately 32 percent in both trials.

Mediation analyses indicated that weight loss was the primary driver of reductions in blood pressure. Improvements in OSA metrics independently contributed to reductions in inflammation, insulin resistance, and triglycerides, although these findings should be interpreted cautiously due to their exploratory nature.

Interpretation and limitations

By addressing both sleep-disordered breathing and obesity, tirzepatide may provide complementary cardiometabolic benefits alongside established PAP therapy. However, definitive evidence on cardiovascular outcomes remains limited.

Future research should assess whether tirzepatide can reduce long-term cardiometabolic risk in selected patients with obesity and moderate-to-severe OSA. The trial excluded individuals with mild OSA, diabetes, or lower body mass index and was not designed to evaluate long-term cardiovascular events or mortality.