JAMA target trial emulation links incretin drugs to lower CPAP use and mortality

A new study published in JAMA on December 22, 2025, found that adults with type 2 diabetes, obesity and obstructive sleep apnea (OSA) who started an incretin drug — a GLP-1 receptor agonist like semaglutide or the dual GLP-1/GIP drug tirzepatide — had lower rates of CPAP use, hospitalization and death compared with those who started an SGLT2 inhibitor, a different class of diabetes medication ^[1].

The study used electronic health record data from the TriNetX research network and included 36,981 adults with an average age of 62.3 ^[1]. Researchers used a method called target trial emulation, matching patients on similar characteristics to mimic a randomized trial using real-world data ^[1]. Compared with SGLT2 inhibitors, starting an incretin drug was linked to a 8% lower risk of needing CPAP (hazard ratio 0.92), a 32% lower risk of death from any cause (hazard ratio 0.68), and a 10% lower risk of hospitalization (hazard ratio 0.90) ^[1].

The benefits were not identical across drugs. Both GLP-1-only drugs and tirzepatide, which also acts on the GIP receptor, were linked to lower CPAP use and mortality, but the reductions were larger with tirzepatide ^[1]. The study population was 70.5% White, 18.6% Black, 2.1% Asian, 6.7% Hispanic and 0.7% Native Hawaiian or Other Pacific Islander ^[1]. Subgroup results were mostly consistent, but the researchers did not find a link between incretin use and lower CPAP use among women or older adults specifically ^[1].

The researchers noted important limits. CPAP use was tracked through insurance procedure codes, which may not accurately reflect how often patients actually used the machines or how severe their sleep apnea was ^[1]. The study also could not fully account for unmeasured factors like income, insurance status, or OSA severity that might have influenced who received which drug and how they fared ^[1].

Why it matters for patients

OSA affects roughly 25% of US adults and often overlaps with type 2 diabetes because both conditions share obesity as a risk factor ^[1]. CPAP, the standard sleep apnea treatment, is effective but many patients struggle to use it consistently ^[1]. This study suggests that for people already living with diabetes, obesity and sleep apnea, an incretin drug might reduce the eventual need for CPAP and lower the risk of hospitalization or death compared with a common alternative diabetes drug, according to the researchers ^[1].

However, this was an observational study, not a randomized clinical trial. It shows an association, not proof that the drugs directly caused the lower death and hospitalization rates. Doctors and patients weighing treatment options for diabetes and OSA do not yet have trial-level evidence confirming these specific outcomes. The study authors themselves stress that unmeasured differences between patients who were prescribed one drug class versus another could explain part of the pattern seen ^[1].

It's also not yet known from this study whether these associations would hold up in a true randomized trial, or how much of the benefit comes from weight loss itself versus other effects of these drugs. The source material does not specify exact average weight change, follow-up duration, or how CPAP use was measured beyond procedure codes.

What happens next

The study was published online in JAMA on December 22, 2025, as a cohort study using retrospective health record data ^[1]. The source material does not describe any planned follow-up randomized trials or specific dates for further research on this question. Given the study's own limitations around confounding and how CPAP use was measured, further prospective research would likely be needed to confirm whether starting an incretin drug directly changes CPAP need, hospitalization, or mortality risk in people with diabetes, obesity, and OSA.