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). 

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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.

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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.


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