Incretin-Based Therapies Not Associated With New-Onset Depression, Self-Harm in T2D

According to study results published in BMJ Open, there were no associations between new-onset depression or self-harm in patients with type 2 diabetes and hyperglycemia treated with either dipeptidyl peptidase-4 (DPP-4) inhibitors or glucagon-like peptide-1 (GLP-1) receptor agonists.

Previous research posited that incretin-based therapies may have neuropsychiatric effects in patients. Both DPP-4 and GLP-1 are incretin-based therapies, and researchers in this study aimed to quantify the associations between these treatments and the composite of either new-onset depression or self-harm. The study population was sourced from a larger population-based cohort study consisting of individuals who received a new diagnosis of type 2 diabetes or a new prescription for any glucose-lowering therapy between 2001 to 2016. The researchers identified two main cohorts: new users of DPP-4 inhibitors or sulfonylurea and new users of GLP-1 receptor agonists or sulfonylurea.

In the DPP-4 inhibitor cohort, DPP-4 inhibitor treatment had 6206 initiators (mean follow-up, 324 days) and sulfonylurea treatment had 22,128 initiators (mean follow-up, 299 days). Comparative analysis showed that DPP-4 inhibitor participants were younger, less often hospitalized, and less likely to exhibit impaired kidney function. DPP-4 participants exhibited a lower incidence of depression or self-harm (8.2 events/1000 person-years) than sulfonylurea participants (11.7 events/1000 person-years). 

In the GLP-1 receptor agonist cohort, GLP-1 receptor agonist treatment had 501 initiators (mean follow-up, 397 days) and sulfonylurea treatment had 16,409 initiators (mean follow-up, 292 days). Comparative analysis showed that GLP-1 receptor agonist participants were younger, more often female, utilized more prescriptions in the year prior to cohort entry, had lower glycated hemoglobin at baseline, and exhibited a slightly higher incidence of depression or self-harm (18.2 events/1000 person-years) than participants receiving sulfonylurea treatment (13.6 events/1000 person-years).

The observational study design was noted as a limitation to the research, as the investigators were unable to capture all relevant potential confounders like depression severity.

The researchers stated that the results provide some reassurance for the safety of incretin-based therapies. “Specifically, our study results suggest that there is not a clinically relevant association between either DPP-4 inhibitors or GLP-1 receptor agonists and depression or self-harm,” they concluded.

Reference

Gamble JM, Chibrikov E, Midodzi WK, Twells LK, Majumdar SR. Examining the risk of depression or self-harm associated with incretin-based therapies used to manage hyperglycaemia in patients with type 2 diabetes: a cohort study using the UK Clinical Practice Research Datalink [published online October 8, 2018]. BMJ Open. doi:10.1136/bmjopen-2018-023830