Weighing the Evidence for the Use of Metformin in Obese Patients

Overweight and obese affect more than 1.9 billion and 600 million people respectively around the world, and 30% of Americans are now obese. It increases mortality in type 2 diabetes, heart disease, stroke, and various cancers. Obese patients' medical expenses are 42% higher than those for people of normal weight. Let's look to the future: if the US's 12.7 million children continue to gain weight, we'll see an additional $1.1 trillion in excess medical expenses.

Only a handful of medications carry an FDA indication for obesity, but metformin (which does not) has weighty evidence supporting its use. Now, an article published in Current Atherosclerosis Reports indicates that the FDA should formally approve metformin for diabetes

Metformin decreases gluconeogenesis and intestinal glucose absorption and increases insulin sensitivity, thus improving peripheral glucose uptake. Moderated insulin levels reduce post-prandial hypoglycemia-induced hunger and carbohydrate craving.

Metformin, like exercise, promotes phosphorylation of the AMP-activated protein kinase system impacting lipogenesis, mitochondrial biogenesis, insulin secretion, hepatic and muscle fatty acid oxidation, and glucose transport. Metformin is also a leptin sensitizer, decreases ghrelin, increases endogenous GLP-1 levels, increases proopiomelanocortin expression, and decreases Neuropeptide Y expression as well.

Several studies demonstrate metformin's potential as a safe weight loss agent:

• A meta-analysis found that metformin produced a 1.1 kg greater weight loss than placebo. Liraglutide, formally approved for obesity, produced a 1.7 kg weight loss in the same meta-analysis.
• The Diabetes Prevention Program, now in its 15th year, found that metformin performed better (2.1 kg weight loss and 31% reduction in diabetes incidence) than placebo. It was less effective than intensive lifestyle interventions, however.
• Metformin’s safety is proven. Lactic acidosis risk in all patients is no greater than the background risk in diabetic patients (3 to 10 per 100,000 patient-years) according a Cochrane review of 347 trials.

Metformin is an underappreciated tool against type 2 diabetes and obesity. Metformin’s action on biochemistry aids long-term weight loss and possesses a well-understood history of safety and tolerability.