No evidence to support incretins as neuroprotective in T2DM

There is not enough irrefutable evidence that dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have positive effects on cognition in patients with type 2 diabetes mellitus (T2DM), according to a study.

Researchers conducted a systematic review and meta-analysis of studies evaluating whether GLP-1 RAs or DPP-4 inhibitors for T2DM had neuroprotective benefits. The initial search from electronic databases yielded 732 records, of which 11 were included in the review and eight in the meta-analysis.

Of the studies, nine were observational and two were interventional, with the duration ranging from 6 months to 7.2 years. The total population comprised 304,258 T2DM patients. Mean age was >60 years in 90.90 percent of studies, while mean body mass index was >25 kg/m² in 72.73 percent. The interventions were monotherapy, combination therapy, and add-on therapy with DPP-4 inhibitors. Metformin and sulfonylurea were the two main comparators.

Pooled data revealed that in the DPP-4 inhibitor arm, there was no significant change in Mini-Mental State Examination (MMSE) scores from baseline to the final evaluations (six studies; mean difference [MD], 0.20, 95 percent confidence interval [CI], −0.75 to 1.15; p=0.68). Likewise, the change in MMSE scores in the DPP-4 inhibitor vs other glucose-lowering treatment arms was not statistically different (MD, 0.57, 95 percent CI, −0.05 to 1.19; p=0.07).

However, DPP-4 inhibitor treatment was associated with a lower risk of dementia (two studies; hazard ratio, 0.52, 95 percent CI, 0.29–0.93; p=0.03).

In the GLP-1 RA arm, one study revealed a downward trend in the risk of dementia, while another revealed no significant difference.

Further clinical studies are needed to establish the effect of DPP-4 inhibitors/GLP-1 RAs on cognitive function in T2DM patients.