Preventing diabetic foot ulcers remains a major clinical challenge in type 2 diabetes mellitus (T2DM), particularly because these complications contribute substantially to hospitalization and lower limb amputation risk. At the ADA Scientific Sessions 2026, a meta-analysis evaluating glucagon-like peptide-1 receptor agonists (GLP-1 RAs) suggested that these therapies may also be associated with lower risk of diabetic foot ulcers (DFUs) and related complications beyond their established metabolic and cardiovascular benefits.
The analysis followed PRISMA guidelines and included randomized controlled trials (RCTs) and observational cohort studies identified through PubMed, Embase, Cochrane Library, and Web of Science. Pooled analyses evaluated incident DFUs as the primary outcome, while secondary outcomes included lower limb amputation (LLA), DFU-related hospitalization, and all-cause mortality. Subgroup analyses assessed treatment duration and GLP-1 RA subtype. The analysis included 31 studies comprising 18 RCTs and 13 cohort studies with 826,412 patients with T2DM.
Findings
- GLP-1 RA therapy was associated with 19% lower risk of incident DFUs compared with control therapies (pooled hazard ratio [HR] 0.81; 95% CI 0.74-0.89; P<0.001).
- Longer treatment duration of more than 400 days showed greater reduction in DFU risk (HR 0.74; 95% CI 0.66-0.83) compared with shorter treatment duration (HR 0.88; 95% CI 0.79-0.98).
- GLP-1 RA use was also associated with lower risk of LLA (HR 0.72; 95% CI 0.61-0.85), DFU-related hospitalization (HR 0.78; 95% CI 0.70-0.87), and all-cause mortality (HR 0.85; 95% CI 0.79-0.92; all P<0.001).
- Moderate heterogeneity was observed across studies (I²=58%), and Egger’s test did not identify significant publication bias (P=0.23).
This meta-analysis showed that GLP-1 RA therapy was associated with lower risk of DFUs and related complications in patients with T2DM. Greater benefit was observed with longer treatment duration, although further large-scale trials are needed to clarify causality and optimal treatment strategies.
