TOPLINE:

Adults with type 2 diabetes (T2D) who initiated and continuously used GLP-1 receptor agonists (RAs) faced a modestly higher risk for new-onset depression over 2.5 years than those with continuous use of SGLT2 inhibitors or sulfonylureas (SU).

METHODOLOGY:

• Researchers conducted a retrospective cohort study to compare the risk for incident depression in adults with T2D who initiated one of the four different classes of glucose-lowering medications (GLP-1 RAs, SGLT2 inhibitors, DPP4 inhibitors, and SU).
• They emulated six target trials using six separate cohorts, each representing one pairwise drug‑class comparison: GLP-1 RAs vs SGLT2 inhibitors, GLP-1 RAs vs DPP4 inhibitors, GLP-1 RAs vs SU, SGLT2 inhibitors vs DPP4 inhibitors, SGLT2 inhibitors vs SU, and DPP4 inhibitors vs SU.
• Cohort sizes ranged from 54,773 to 227,414 and included patients aged ≥ 18 years who received a qualifying medication between January 2014 and December 2022 and had no evidence of depression or dispensing of the medications of interest in the 2 years before drug initiation.
• Exposure to medications was ascertained using pharmacy dispensing or claims data; patients were considered exposed during prescription coverage periods, which were defined as twice the number of days of supply.
• The primary outcome was time to incident depression diagnosis within 2.5 years after drug initiation, identified using diagnostic codes from inpatient, emergency department, or outpatient encounters.

TAKEAWAY:

• Sustained GLP-1 RA use was associated with a higher risk for incident depression than sustained SGLT2 inhibitor use (risk difference [RD], 1.0%; 95% CI, 0.6%-1.4%) and sustained SU use (RD, 1.8%; 95% CI, 1.3%-2.4%), after adjustment for confounders.
• SGLT2 inhibitor use was associated with a lower risk for incident depression than DPP4 inhibitor use (RD, -0.7%; 95% CI, -1.2% to -0.2%).
• Overall, sustained use of GLP 1 RAs and DPP4 inhibitors showed the highest risks for incident depression, followed by SU, whereas SGLT2 inhibitors showed the lowest risk.
• After accounting for time-varying information on demographics, diagnoses, procedures, medications, laboratory results, and vital signs, only the comparison between GLP-1 RAs and SGLT2 inhibitors remained significant, with GLP-1 RA use associated with a greater risk for incident depression than SGLT2 inhibitor use.

IN PRACTICE:

“Patients and clinicians may want to consider these findings, along with other information about medication benefits and risks, when initiating a glucose-lowering medication,” the authors wrote. 

SOURCE:

The study was led by Stephanie A. Hooker, PhD, HealthPartners Institute, Minneapolis. It was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

Unmeasured variables including medication costs, convenience, and side-effects could have influenced initial medication selection. Important lifestyle factors such as physical activity, diet, and sleep patterns were not captured. The limited look-back period and potential underdiagnosis may have resulted in including patients with previous depression.

DISCLOSURES:

The study was funded by the Patient-Centered Outcomes Research Institute. Some authors disclosed relationships, including research support from the US National Institutes of Health and pharmaceutical companies as well as participation in clinical research or consulting; one author’s employer contracts for his services, and he receives no direct personal income from these activities.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.