Comparative efficacy and safety of liraglutide versus metformin, naltrexone/bupropion, and phentermine-topiramate in psychiatric patients

Published Feb 23, 2026Therapeutic advances in psychopharmacology

Effectiveness and safety of liraglutide compared to metformin, naltrexone/bupropion, and phentermine-topiramate in people with mental health conditions

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Abstract

Liraglutide (LIRA) was associated with a 3.45% greater weight reduction compared to metformin (MET) in a cohort of 117 psychiatric outpatients.

Weight loss after 12 weeks was greater with LIRA compared to MET, with a statistically significant difference.
Female sex and full-time employment were linked to reduced weight loss among the participants.
A trend suggested that a higher number of psychotropic medications with moderate weight-gain risk may lead to greater weight reduction.
No significant differences in adverse event incidence were found among the antiobesity medications studied.
Early discontinuation rates varied by medication type, with MET having the lowest rate at 39.1% and phentermine-topiramate (PT) having the highest at 72.2%.

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BACKGROUND: Psychiatric patients have a high risk of obesity, frequently due to psychotropic medication-induced weight gain. However, real-world comparative data on antiobesity medications (AOMs) in this population remain rare.

OBJECTIVES: To compare short-term weight-loss efficacy, adverse events (AEs), and early discontinuation (ED) among psychiatric outpatients taking liraglutide (LIRA), naltrexone/bupropion, phentermine-topiramate (PT), or metformin (MET).

DESIGN: Retrospective observational cohort study.

METHODS: We conducted a 12-week retrospective chart review of 117 psychiatric outpatients with International Classification of Diseases, 10th Revision, F01-F99 diagnoses. Percent weight change over time was analyzed using linear mixed-effects models. AEs and ED were compared across treatment groups.

RESULTS: Compared with MET, LIRA was associated with a greater percent weight reduction (estimate -3.45%, 95% confidence interval (CI) -5.35 to -1.55, < 0.001), with a significant treatment-by-time interaction at 12 weeks ( = 0.019). Female sex and full-time employment were associated with attenuated weight loss, and the number of concomitant psychotropic medications with moderate weight-gain risk showed a trend toward greater weight reduction ( = 0.066). No significant differences were observed in AE incidence across AOMs. ED rates differed by drug type ( = 0.017), being lowest in the MET group (39.1%) and highest in the PT group (72.2%). p p p p

CONCLUSION: In this real-world psychiatric cohort, LIRA was associated with greater short-term weight loss than MET without an increased observed frequency of AEs. ED rates varied across AOMs. These findings should be interpreted cautiously, given the observational design and short follow-up period, and require confirmation in larger, long-term studies.

Key numbers

−6.30%

Weight Reduction by LIRA

Mean percent reduction in body weight at 12 weeks.

39.1%

Early Discontinuation Rate for MET

Lowest early discontinuation rate among the studied medications.

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Comparative efficacy and safety of liraglutide versus metformin, naltrexone/bupropion, and phentermine-topiramate in psychiatric patients

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