Dementia risk similar with GLP-1 receptor agonists, DPP-4 inhibitors

Rates of dementia were similar among older adults taking glucagon-like peptide-1 (GLP-1) receptor agonists or dipeptidyl peptidase-4 (DPP-4) inhibitors as second-line therapy for type 2 diabetes, a study found.

The target trial emulation used Medicare data on fee-for-service beneficiaries aged 66 years or older with diabetes who used metformin, did not have dementia at baseline, and initiated a GLP-1 receptor agonist or DPP-4 inhibitor between January 2017 and December 2018. A total of 2,418 patients initiating GLP-1 receptor agonists were matched to 4,836 initiating DPP-4 inhibitors (mean age, 71 years; 55% women). Results were published by Annals of Internal Medicine on July 22.

Over a median follow-up of 1.9 years, dementia was diagnosed in 96 patients on GLP-1 receptor agonists and 217 taking DPP-4 inhibitors, for an estimated risk difference at 30 months of −0.93 percentage points (95% CI, −2.33 to 0.23 percentage points) and a risk ratio of 0.83 (95% CI, 0.61 to 1.05). The risk ratios were 0.64 (95% CI, 0.46 to 0.93) in those younger than 75 years and 1.22 (95% CI, 0.74 to 1.66) in those ages 75 years or older.

Overall, the study indicated no clear differences in dementia rates between older patients with diabetes by whether they were taking GLP-1 receptor agonists or DPP-4 inhibitors, the study authors concluded. However, they added that “subgroup analyses suggest that GLP-1 [receptor agonists] may confer some advantage over DPP4 [inhibitors] among adults younger than 75 years, whereas effect estimates were very imprecise among those aged 75 years or older and were inconclusive due to wide confidence intervals.”

Any causal relationship between GLP-1 receptor agonists and dementia remains unclear, and randomized trials with longer follow-up are warranted to better understand any association, the authors said.