SURMOUNT-OSA

SURMOUNT-OSA is a Phase 3 randomised controlled trial evaluating tirzepatide for the treatment of moderate-to-severe obstructive sleep apnoea (OSA) in adults with obesity. Published in NEJM October 2024 (PMID 38912654), it was conducted as two parallel sub-trials (intervention-specific appendices): ISA-1 enrolled participants not currently on positive airway pressure (PAP) therapy; ISA-2 enrolled participants who were on PAP therapy. Both ran for 52 weeks (n=469 total: ISA-1 n=234, ISA-2 n=235). Tirzepatide was escalated to maximum tolerated dose (10 or 15mg once-weekly).

Primary outcome — AHI reduction: At baseline, mean AHI was 51.5 events/h (trial 1) and 49.5 events/h (trial 2) — both in the severe OSA range. At 52 weeks:

• Trial 1 (no PAP): Tirzepatide −25.3 events/h vs placebo −5.3 events/h; treatment difference −20.0 events/h (95% CI −25.8 to −14.2; P<0.001)
• Trial 2 (on PAP): Tirzepatide −29.3 events/h vs placebo −5.5 events/h; treatment difference −23.8 events/h (95% CI −29.6 to −17.9; P<0.001)

These reductions represent a shift from severe OSA toward moderate or mild categories for many participants — clinically meaningful.

Ontology SURMOUNT-OSA [evidence_for] Tirzepatide SURMOUNT-OSA [relates] Obstructive Sleep Apnea SURMOUNT-OSA [relates] Weight Loss in T2D

Secondary outcomes: All prespecified key secondary endpoints improved significantly with tirzepatide vs placebo: sleep apnoea-specific hypoxic burden reduced; high-sensitivity C-reactive protein (hsCRP) reduced; systolic blood pressure reduced; patient-reported sleep impairment and disturbance improved. Weight loss occurred in both arms but substantially greater with tirzepatide — and mediates much of the OSA improvement, since upper-airway fat deposition is a key contributor to OSA pathophysiology.

Adverse events: GI adverse events (nausea, vomiting, diarrhoea) were the most common, consistent with the broader tirzepatide profile — mostly mild to moderate in severity.

Ontology SURMOUNT-OSA [relates] Cardiovascular Risk SURMOUNT-OSA [relates] Side Effects Profile

Vault context — T2D relevance: SURMOUNT-OSA was not restricted by T2D status — it enrolled patients based on OSA + obesity regardless of T2D. Approximately 20-40% of T2D patients have OSA comorbidity (OSA and T2D share obesity as a common driver). For T2D patients who also have OSA, SURMOUNT-OSA provides directly applicable evidence that tirzepatide reduces OSA severity and improves cardiometabolic markers simultaneously. The mechanism is primarily (but not exclusively) weight-mediated: upper-airway fat pad reduction reduces pharyngeal collapsibility. Whether there are weight-independent neural or respiratory effects of GIP/GLP-1 agonism on upper-airway tone is under investigation. Importantly, OSA improvement was also seen in ISA-2 (patients already on CPAP) — suggesting tirzepatide reduces underlying OSA burden even with existing mechanical treatment.

Ontology SURMOUNT-OSA [relates] Type 2 Diabetes SURMOUNT-OSA [part-of] Tirzepatide

Key Numbers

Practical Interpretation

• Who this applies to: T2D patients with obesity-related OSA — a common overlap (~20-40% of T2D adults)
• Implication: Tirzepatide addresses OSA mechanistically (weight-mediated + possible direct effects), not just symptomatically
• vs CPAP: CPAP controls symptoms but does not treat the underlying obesity-driven OSA; tirzepatide addresses the root cause
• Caveat: Population was obesity + OSA, not T2D-specific; T2D subgroup data not separately reported
• CV significance: OSA is associated with major cardiovascular complications; reducing AHI and hsCRP in these patients may contribute to CV risk reduction

Connections

• Tirzepatide — evidence_for (OSA treatment)
• Obstructive Sleep Apnea — primary condition studied
• Weight Loss in T2D — mechanism (weight loss drives AHI reduction)
• Cardiovascular Risk — relates (OSA-CV nexus)

Sources

• SURMOUNT-OSA Phase 3 (NEJM 2024)