Continuous GLP-1 Agonist Use Reduces All-Cause Mortality by 19% in Hemodialysis Patients

Patients with Type 2 Diabetes (T2D) undergoing hemodialysis face elevated risks for cardiovascular events and mortality. While glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors are both used for glycemic control, their comparative effectiveness on mortality in this specific, vulnerable population remains largely unknown. Current standard-of-care often focuses on glycemic management, but understanding broader survival benefits is crucial given the high comorbidity burden in End-Stage Renal Disease (ESRD) patients.

Researchers conducted a target trial emulation using US Renal Data System and Medicare claims data from 2011 to 2021. They compared new users of GLP-1 agonists (n=3671) against DPP-4 inhibitors (n=12,039) among patients who had survived at least 90 days on in-center hemodialysis. The study utilized inverse probability of treatment weighting (IPTW) and Cox proportional hazards models to estimate hazard ratios (HRs) for all-cause, cardiovascular, and infection mortality. Both intention-to-treat and per-protocol analyses (censoring at medication discontinuation) were performed.

In the intention-to-treat analysis, GLP-1 agonist initiation was not significantly associated with reduced all-cause mortality compared to DPP-4 inhibitors, showing an HR of 0.98 (95% CI: 0.89-1.07). Similarly, cardiovascular mortality (HR 1.06, 95% CI: 0.92-1.23) and infection mortality (HR 0.83, 95% CI: 0.54-1.26) showed no significant difference. However, the per-protocol analysis, which accounted for continuous medication use, revealed a significant benefit:

Continuous GLP-1 agonist use was associated with an 19% reduction in all-cause mortality (HR 0.81, 95% CI: 0.68-0.96) compared to DPP-4 inhibitors. Cardiovascular mortality also trended lower (HR 0.89, 95% CI: 0.69-1.13), and infection mortality was reduced (HR 0.65, 95% CI: 0.37-1.14), though not reaching statistical significance. A notable finding was the high discontinuation rate: 53% for GLP-1s versus 42% for DPP-4s within one year. GLP-1s were also associated with a slightly increased risk of gastrointestinal symptoms (HR 1.11, 95% CI: 1.02-1.20).