The Impact of Metformin on Weight and Waist Circumference in Patients Treated With Clozapine: A One-Year Retrospective Cohort Study

Background: Metformin shows potential in combating clozapine-induced weight gain (CIWG). However, current evidence for its use remains limited. Through an audit we determined the prevalence of metformin use among clozapine-treated patients and its impact on weight and waist circumference (WC). Methods: This retrospective cohort study examined electronic medical records of community-based clozapine patients under the care of metropolitan community mental health teams within the Central Adelaide Local Health Network (CALHN) from January 2014 to June 2023. We included patients treated with clozapine both with and without metformin, above 18 years of age, with complete physical monitoring data at baseline, 6, and 12 months. Results: There were 357 patients, who met study criteria. Metformin was prescribed to 23% of patients, of whom 78% had diabetes. At baseline, WC was > 101 cm in 71% of males and > 87 cm in 86% of females, placing them at increased risk of weight-related comorbidities, including cardiovascular disease, cancer, and death. After 1 year, males and females in the highest risk group for WC-related comorbidities increased to 76.3% and 95.4%, respectively. Co-prescription of metformin with clozapine was associated with unadjusted mean weight loss (-1.67 kg) and decrease in WC (-1.00 cm). Patients not using metformin gained weight (0.68 kg) and WC (2.49 cm). Using a linear mixed-effects models adjusting for repeated measurements, age, sex, and type 2 diabetes, over 12 months, patients treated with metformin were 3.08 kg lighter than those not taking metformin (95% confidence interval [CI]: 0.54-5.62, p = 0.018). Similar models suggested patients treated with metformin showed an average 2.83 cm decrease in WC compared with those not taking metformin (CI: 0.26-5.40, p = 0.03). There was no significant interaction between difference from baseline in weight or WC and metformin dose (p > 0.05). Discussion/Conclusion: The prevalence of metformin use for CIWG appears low in this cohort, where over 84% of patients were overweight or obese. Metformin use was associated with a significantly lower incidence of weight and WC gain over 12 months. Pharmacists are crucial for educating clinicians and patients about the benefits of metformin for reducing CIWG.