Metformin for Weight Loss?
Metformin effective for weight loss?
According to findings of the National Health and Nutrition Examination Survey, 34.9% of adults aged 20 years or over are obese (body mass index [BMI] ≥30 kg/m2).
Obesity is a risk factor for many chronic diseases but is best known for its role in metabolic syndrome, which can lead to type 2 diabetes (T2D) as well as cardiovascular disease.
Metformin is the first-line pharmacologic treatment for patients with T2D and can be useful in preventing or delaying diabetes in patients with prediabetes, defined as a glycated hemoglobin (A1c) from 5.7% to 6.4%.
Metformin is a valuable treatment for the majority of patients with T2D due its high rate of efficacy, low risk for hypoglycemia, few side effects, ease of use, and low cost.
Additionally, metformin has beneficial effects on weight loss in T2D and possibly in polycystic ovary syndrome (PCOS) and obesity without diabetes.
The only approved indication for metformin is T2D; thus, most of the understanding of the effect of metformin on weight loss has been gained from research in patients with T2D.
The mechanism of action for metformin is unique compared with other antihyperglycemic agents. Metformin decreases the production of glucose in the liver, decreases the absorption of glucose in the intestine, and improves insulin sensitivity through increasing muscle glucose uptake and use.
Metformin induces weight loss most likely through a loss of adipose tissue rather than a change in energy expenditure, as is seen with exercise.
Two large studies by the Diabetes Prevention Program Research Group assessed weight loss with metformin. In the study published in 2009, patients randomly assigned to receive lifestyle treatment initially lost weight but gradually regained the lost weight over the 10-year follow-up period.
Patients randomly assigned to receive metformin lost less weight at the beginning of the study (2.5 kg) but were able to sustain the weight loss over 10 years.
In the study published in 2012, participants in the original study were offered the chance to continue metformin in an open-label fashion. Overall weight loss during the open label period of 7-8 years was 1.9 kg. In patients considered highly adherent to metformin, the average weight loss was 3.1 kg compared with baseline.
In a study comparing metformin, exercise about 190 minutes per week, and the combination of the two in adults with impaired glucose tolerance T2D patients excluded metformin and metformin plus exercise decreased body weight more than exercise alone.
Metformin alone also decreased caloric intake but not percent body fat or central body fat.
In a recent randomized controlled trial comparing metformin, oral contraceptive pills (OCPs), and the combination of the two in patients with PCOS without T2D, metformin alone or with OCPs decreased weight and BMI. The median decrease in weight with metformin at 12 months was 3 kg 25th and 75th quartiles; -10.3, 0.6. OCP use was associated with increased weight changes of 1.2 kg (25th and 75th quartiles; -0.8, 3.0), and the combination decreased weight by 1.9 kg (25th and 75th quartiles; -4.9, 0.1). One patient in the metformin group dropped out due to nausea; no other side effects or adverse events were reported.
In a systematic review that included 12 randomized controlled trials in women with PCOS, metformin produced a significant decrease in BMI when compared with placebo; however, many of the studies were not adequately powered, so the conclusion must be interpreted with caution and other clinical factors for individual patients considered. The review did not mention risk for hypoglycemia or if patients had impaired glucose tolerance.
Some studies have looked at metformin in overweight and obese euglycemic patients.
In a 6-month case control study, patients with a BMI of 27 kg/m2 or higher and an average A1c of 5.6% received metformin with a dose based on their BMI. The average weight loss over 6 months was 5.8 ± 7.0 kg, with a range of -35 kg to +13 kg. About 20% of the patients treated with metformin lost no weight. Gastrointestinal side effects were reported, which decreased with slower dose titration. No events of hypoglycemia were reported.
In a systematic analysis, five studies with a primary outcome of weight loss showed that metformin treatment resulted in a range of weight loss between 2.9 and 9.0 kg. None of the studies were randomized or placebo-controlled, so interpretation is difficult. Gastrointestinal complaints were the most common adverse events, and hypoglycemia was not an issue.
In conclusion, metformin does have a modest effect on weight loss in patients with T2D, PCOS, and possibly in overweight and obese euglycemic patients. More studies, especially randomized controlled trials, are needed to determine the duration and dose of metformin and potential long-term adverse effects in patients without T2D. Patients should be advised that metformin is unlikely to cause a drastic decrease in weight, and lifestyle modifications should be recommended. Renal function and blood glucose should be monitored in patients receiving metformin