Could commonly used glucose-lowering therapies also influence future neurologic outcomes? A large multinational observational study published in Diabetes, Obesity and Metabolism found that use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) was associated with lower rates of incident Parkinson's disease compared with sulfonylureas in routine clinical practice.

The cohort study used nationwide health registers from Denmark, Norway, and Sweden and applied an active-comparator, new-user design. The analysis included 158,961 new users of GLP-1 RAs and 188,065 new users of sulfonylureas aged 45 years or older. The mean age was 65 years, and 43% were women. Liraglutide accounted for most GLP-1 RA exposure time (72.9%), followed by semaglutide (13.4%), exenatide (7.3%), dulaglutide (5.1%), and lixisenatide (1.3%).

The primary outcome was the first-ever Parkinson's disease or Parkinson's disease dementia recorded in national patient registers. Incidence rates were 5.2 per 10,000 person-years among GLP-1 RA users and 8.0 per 10,000 person-years among sulfonylurea users. After propensity score weighting and confounding adjustment, GLP-1 RA use was associated with a lower rate of incident Parkinson's disease (adjusted hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.68-0.96).

Sensitivity analyses supported the main findings. In a 2-year lag-time analysis, the HR was 0.84 (95% CI, 0.70-1.02). After excluding or censoring users of dipeptidyl peptidase-4 inhibitors, the HR was 0.74 (95% CI, 0.60-0.93). Associations were also consistent across sex and age subgroups. These results suggest GLP-1 RAs may have relevance beyond glycemic management, although confirmation in additional studies is needed.