GLP-1 Analogs Are Superior in Mediating Weight Loss But Not Glycemic Control in Diabetic Patients on Antidepressant Medications: A Retrospective Cohort Study

Carolyn L. Gonzalez, MD; Salman Azim, MD; Susanne U. Miedlich, MD

Prim Care Companion CNS Disord 2021;23(5):20m02868

ABSTRACT

Objective: Both antipsychotic and antidepressant medications have been associated with weight gain and hyperglycemia. Our previously published retrospective cohort study suggests that GLP-1 (glucagon-like peptide-1) analogs may be superior to alternative regimens for both glycemic and weight control in patients on antipsychotic plus/minus antidepressant medications. In the current study, we asked whether GLP-1 analogs or SGLT-2 (sodium-glucose-transporter-2) inhibitors would be similarly beneficial in patients on antidepressant medications alone.

Methods: In this retrospective cohort study, we included all patients with type 2 diabetes on antidepressant medications referred to our endocrine clinics between January 1, 2016, and January 1, 2017. Overall, 61 patients were started on a GLP-1 analog, 9 patients were started on an SGLT-2 inhibitor, and 134 were on alternative regimens (controls).

Results: The groups did not differ in age, sex, ethnicity, and glycosylated hemoglobin (HbA_1c) levels, although body mass index levels were higher in patients started on a GLP-1 analog (P < .0001). After 12 months, patients on GLP-1 analogs lost 4 kg, patients on SGLT-2 inhibitors lost 2.4 kg, and controls gained 0.8 kg (P < .001 for controls versus GLP-1 analog group). Subanalyses revealed that GLP-1 analog–related weight loss was most notable in women and patients on selective serotonin reuptake inhibitors. On the other hand, all serotonin-norepinephrine reuptake inhibitor users lost weight over time, independent of the antidiabetic regimen applied. In contrast to the above noted differences in weight control, HbA_1c reductions were comparable and somewhat diminished in all patients on antidepressant medications (−0.3% to 0.6%).

Conclusions: In this retrospective cohort study, we confirm superiority of GLP-1 analogs in mediating weight loss in patients on psychotropic and, more specifically, antidepressant medications. We also note overall blunted glycemic improvements in patients on antidepressant medications, a finding that was independent of the treatment strategy used. It could be a result of mental distress or suboptimal self-care and clearly requires further attention by future, prospective studies.

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