Patients with diabetes face repeat major adverse limb events (MALE) after their first episode, and these incidents substantially raise risks for heart issues as well as further amputations. Glucose-lowering therapies for secondary prevention remain limited in this vulnerable population. This study directly compares GLP-1 receptor agonists with DPP-4 inhibitors to assess their impact. The results were published in JAMA Network Open. 
Massive Taiwan Database Review
Researchers analyzed data from the Taiwan National Health Insurance Research Database spanning October 2012 to December 2023, and they included 17,288 patients who had diabetes along with a history of MALE defined as chronic limb-threatening ischemia, lower limb revascularization, or nontraumatic minor and major amputation. The cohort had a mean age of 70.7 years with 57.9% male participants, 1583 of whom initiated GLP-1 RAs such as liraglutide, dulaglutide, or semaglutide while 15,705 started DPP-4 inhibitors. 
GLP-1 RAs Show Broad Protection
The primary outcome of lower limb revascularization or nontraumatic major and minor amputation occurred less often with GLP-1 RAs (SHR 0.90, 95% CI 0.83-0.97), and this benefit stemmed primarily from a marked reduction in amputations (SHR 0.86, 95% CI 0.75-0.98). GLP-1 RAs also lowered risks of major adverse cardiovascular events (HR 0.62, 95% CI 0.58-0.65), cardiovascular death (HR 0.57, 95% CI 0.53-0.61), all-cause mortality (HR 0.63, 95% CI 0.60-0.66), and progression to long-term dialysis (SHR 0.61, 95% CI 0.54-0.70).
Prioritize GLP-1 RAs in High-Risk Fee
In this high-risk group with prior MALEs, GLP-1 RAs outperformed DPP-4 inhibitors across limb, cardiovascular, mortality, and kidney outcomes, so clinicians should favor them for secondary prevention.