Little difference in dementia risk with SGLT-2s vs. dulaglutide

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors were associated with lower risk for dementia than the glucagon-like peptide-1 (GLP-1) receptor agonist dulaglutide in a recent study.

Researchers in South Korea used a national database to perform a target trial emulation comparing the risk for dementia with SGLT-2 inhibitors and dulaglutide. Data were obtained between 2010 and 2022 and included patients ages 60 years and older who had type 2 diabetes and were starting treatment with dulaglutide or an SGLT-2 inhibitor. The study's primary outcome was presumed clinical onset of dementia, defined as the year before the date of dementia diagnosis. Follow-up began at treatment assignment and ended at dementia onset, death, or Dec. 31, 2022, whichever came first. Five-year risk ratios and risk differences comparing SGLT-2 inhibitors with dulaglutide were estimated in a 1:2 propensity score-matched cohort, with adjustment for confounders. The results were published Aug. 27 by Annals of Internal Medicine.

The trial included 12,489 patients starting SGLT-2 inhibitor treatment (51.9% dapagliflozin and 48.1% empagliflozin) and 1,075 patients starting dulaglutide treatment. Mean body mass index was 26.2 kg/m², mean age was 66.8 years, 43.6% had hypertension, 23.7% had been hospitalized at least once, and 10.3% had ED visits during the baseline period. Over a median follow-up of 4.4 years (interquartile range, 3.3 to 5.3 years) in the matched cohort, 69 patients in the SGLT-2 inhibitor group and 43 in the dulaglutide group had clinical onset of dementia, with an estimated five-year risk difference of −0.91 percentage point (95% CI, −2.45 to 0.63 percentage point) and an estimated risk ratio of 0.81 (95% CI, 0.56 to 1.16). The estimates were similar for the primary outcome after stratification by age, sex, use of insulin in the past year, history of cardiovascular disease, and hypertension.

The authors noted that their results could have been affected by residual confounding and that newer, more effective GLP-1 receptor agonists were not studied, among other limitations. “In conclusion, we found little difference in the risk for dementia for SGLT2 inhibitors compared with dulaglutide in our data. However, whether these findings generalize to newer GLP-1 [receptor agonists] is uncertain,” they wrote. “Further studies that incorporate newer drugs in these classes and better address residual confounders, including duration of diabetes and hemoglobin A1c levels, are required.”