GLP-1RA Use May Lower Dementia, Cognitive Impairment Risks

Use of cardioprotective glucose-lowering therapies does not affect all-cause dementia risk, according to results of a study published in JAMA Neurology.

Observational data suggest that sodium-glucose cotransporter-2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) drug classes may have neuroprotective effects.

To assess whether glucose-lowering medications decrease dementia risk, investigators from the University of Galway in Ireland conducted a systematic review and meta-analysis of studies through June 2024. Included studies were randomized clinical trials of SGLT2is, GLP-1RAs, metformin, and pioglitazone that reported dementia or cognitive impairment as an outcome.

The analysis included a total of 26 studies, which were published between 2015 and 2024 and mostly (n=24) conducted in multiple countries. The pooled sample size comprised 164,531 patients (mean [SD] age, 64.4 [3.5] years), of whom 34.9% were women.

During a mean follow-up of 31.8 months, 93 patients who received glucose-lowering therapy and 119 who received control treatment were diagnosed with dementia or cognitive impairment. Glucose-lowering therapy was not associated with decreased risk for dementia or cognitive impairment (odds ratio [OR], 0.83; 95% CI, 0.60-1.14; I², 6.6%).

However, stratified by medication class, dementia or cognitive impairment risk was lower with GLP-1RAs (OR, 0.55; 95% CI, 0.35-0.86) but not with SGLT2is (OR, 1.20; 95% CI, 0.67-2.17).

Stratified by dementia subtypes, glucose-lowering therapy was not related with risk for vascular dementia (OR, 0.45; 95% CI, 0.19-1.07; I², 0.0%), Alzheimer dementia (OR, 1.20; 95% CI, 0.82-1.77; I², 0.0%), or Lewy body dementia (OR, 0.58; 95% CI, 0.12-2.86; I², 0.0%).

Similarly, stratified by drug class, GLP-1RA use was not associated with lower risk for vascular dementia (OR, 0.38; 95% CI, 0.18-1.61) or Alzheimer dementia (OR, 1.85; 95% CI, 0.52-6.57), SGLT2i use was not associated with reduced vascular dementia (OR, 0.35; 95% CI, 0.09-1.36) or Alzheimer dementia (OR, 1.99; 95% CI, 0.59-6.71) risk, and pioglitazone use was not associated with reduced Alzheimer dementia risk (OR, 1.07; 95% CI, 0.70-1.65).

In 3 trials, no significant change in cognitive scores was associated with glucose-lowering medications from baseline to follow-up.

The major limitation of this analysis was the presence of heterogeneity between comparison interventions.

The study authors concluded, “In this meta-analysis of randomized clinical trials, glucose-lowering therapy with GLP1-RAs, but not SGLT2is or pioglitazone, was associated with a statistically significant reduction in dementia or cognitive impairment.”

This article originally appeared on Endocrinology Advisor