In this issue of the Journal, the study by Jarskog et al. (13) is the largest study to date of metformin in antipsychotic-treated patients (N=146). It compared 16 weeks of 1,000 mg of metformin twice daily (mean final dose=1,887 mg [SD=292]) with placebo in antipsychotic-treated adults. Additionally, all participants received a standardized healthy lifestyle intervention, deliverable in usual care settings. Generalizability was enhanced by including patients with a body mass index (BMI) ≥27 (mean=34.6 [SD=5.9]) independent of timing and amount of prior weight gain, different levels of chronicity of psychosis, comorbid psychiatric conditions, and treatment with two antipsychotics or psychiatric comedications, excluding only diabetic individuals. Furthermore, for the first time, exploratory moderator and mediator analyses of metformin’s efficacy were performed. Metformin was associated with a −3.0-kg weight loss (95% confidence interval [CI]=−4.0 to −2.0) that was significantly greater than the small weight reduction of −1.0 kg (95% CI=−2.0 to 0.0) in the placebo group. This weight reduction translated into a −0.7 (95% CI=−1.1 to −0.2) greater BMI reduction compared with placebo. However, the mean percent weight loss was only 2.8% of baseline weight with metformin compared with 1.0% with placebo, and only 17.3% and 9.8% of participants, respectively, lost ≥5% of their baseline body weight. A linear time-by-treatment interaction suggests that weight loss could possibly continue beyond 16 weeks. Additionally, the fact that the placebo group lost 1 kg over 4 months suggests that healthy lifestyle intervention can reduce some weight in motivated patients, like those participating in research. Metformin was also associated with significantly lower triglyceride and hemoglobin A1C levels than placebo. The latter findings indicate that the weight reduction with metformin was associated with important additional benefits regarding lipid and glucose metabolism, which are closely related to the risk for diabetes and cardiovascular disease (1). Notably, metformin was well tolerated. Furthermore, younger age (<44 years old), lower BMI (<33), male sex, and nonsmoking status were associated with greater weight loss with metformin. The authors noted the inadequate power for these post hoc analyses, which likely contributed to the failure to discern significant benefits in women, who comprised only 30% of the study sample.