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Despite the known glucose-lowering effects of metformin, more recent clinical interest lies in its potential as a weight loss drug. Herein, we discuss the potential mechanisms by which metformin decreases appetite and opposes unfavorable fat storage in peripheral tissues.Many individuals struggle to maintain clinically relevant weight loss from lifestyle and bariatric surgery interventions. Long-term follow-up from the Diabetes Prevention Program demonstrates that metformin produces durable weight loss, and decreased food intake by metformin is the primary weight loss mechanism. Although the effect of metformin on appetite is likely to be multifactorial, changes in hypothalamic physiology, including leptin and insulin sensitivity, have been documented. In addition, novel work in obesity highlights the gastrointestinal physiology and circadian rhythm changes by metformin as not only affecting food intake, but also the regulation of fat oxidation and storage in liver, skeletal muscle, and adipose tissue.Metformin induces modest weight loss in overweight and obese individuals at risk for diabetes. A more detailed understanding of how metformin induces weight loss will likely lead to optimal co-prescription of lifestyle modification with pharmacology for the treatment of obesity independent of diabetes.