Metformin for the prevention of clozapine‐induced weight gain: A retrospective naturalistic cohort study

Abstract

Objective: Clozapine is presently the sole antipsychotic with an indication for treatment-resistant Schizophrenia, but is associated with significant weight gain and other metabolic aberrations. This retrospective chart review aimed to evaluate the effectiveness of adjunctive metformin in preventing clozapineinduced weight gain. Methods: We conducted a retrospective chart review of patients newly initiated on clozapine at the Centre for Addiction and Mental Health in Canada, from November 2014 to April 2021. Our primary outcome was body weight at 6 and 12 months after clozapine initiation. Other metabolic parameters served as secondary outcomes. Results: Among 396 patients (males: 71.5%, mean age: 42.8 years) initiated on clozapine, 69 were on metformin or prescribed it ≤3 months after clozapine initiation. The clozapine+metformin group demonstrated less weight gain compared with the clozapine-only group at 6 months (clozapine+metformin: À0.15 kg [SE = 1.08] vs. clozapine-only: 2.99 kg, SE = 0.54) and 12 months after clozapine initiation (clozapine+metformin: À0.67 kg, SE = 1.22 vs. clozapine-only: 4.72 kg, SE = 0.67). Adaptive changes were also observed for fasting glucose (F = 3.10, p = 0.046) and triglycerides (F = 8.56, p < 0.001) in the clozapine+metformin group compared with clozapine only. Conclusion: In this large retrospective naturalistic cohort study, coprescription of clozapine and metformin was associated with less weight gain and related metabolic dysfunction at 6 and 12 months after initiation versus clozapine alone. These findings provide evidence for the effectiveness of metformin in preventing clozapine-induced weight gain; larger randomized controlled trials are needed to confirm these results.

Sicherheitsaspekte bei der Behandlung mit Clozapin

“…Aufgrund fehlender Grenzwerte soll eine Ernährungsberatung und die Aufforderung zu ausreichender Bewegung durchgeführt werden, auch eine adjuvante Therapie mit z. B. Metformin kann erwogen und gegebenenfalls im Sinne der Prophylaxe auch zeitgleich eingesetzt werden [ 21 , 22 ].…”

Antipsychotic‐induced weight gain: Is the weight over? New guidelines needed

“…Few studies have examined the role of metformin in the prevention of AiWG. A recent retrospective cohort study included in this current issue showed that metformin was associated with less weight gain compared to the control group after 6 (−0.15 kg vs. 2.99 kg) and 12 months (−0.67 kg vs. 4.72 kg) in 396 participants newly initiated on clozapine, of which 69 were on metformin ≤3 months after clozapine initiation 37 . Adverse events of metformin are mainly gastro‐intestinal.…”

“…A recent retrospective cohort study included in this current issue showed that metformin was associated with less weight gain compared to the control group after 6 (À0.15 kg vs. 2.99 kg) and 12 months (À0.67 kg vs. 4.72 kg) in 396 participants newly initiated on clozapine, of which 69 were on metformin ≤3 months after clozapine initiation. 37 Adverse events of metformin are mainly gastro-intestinal. A placebo-controlled study randomized 25 participants with schizophrenia, schizoaffective, bipolar or depressive disorder to olanzapine and metformin 2000 mg/day or olanzapine and placebo for 24 weeks.…”

Rethinking Clozapine: Lights and Shadows of a Revolutionary Drug

“…The increase is usually more than 7% of the patient's body weight [230]. Fortunately, this adverse effect can be countered with an adequate diet and regular physical activity or, as a second option, the administration of controlled-release metformin may be considered [231]. Noteworthily, while most patients who experienced hyperglycaemia with Clozapine had risk factors for diabetes, hyperglycaemia was also reported in patients without risk factors.…”