Metformin may be used off-label for weight management in people predisposed to diabetes
Does metformin cause weight loss? | How does metformin work for weight loss? | Who can take metformin for weight loss? | Other diabetic medications that cause weight loss | How to maximize metformin benefits
Metformin (brand name Glucophage and Fortamet) is a commonly used medication to help lower and manage blood sugar in people with Type 2 diabetes. Metformin works by helping the body respond better to the insulin it makes naturally, decreasing the amount of sugar the liver makes, and decreasing the amount of sugar the intestines absorb. This prescription medication can help keep blood sugar (blood glucose) levels in target range to prevent or delay long-term, serious health problems, such as heart disease, vision loss, and kidney disease. Additionally, maintaining blood sugar levels can help improve energy and mood. Metformin is available as a tablet, extended-release tablet, and oral solution.
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Does metformin cause weight loss?
According to the American Diabetes Association, being overweight raises the risk for Type 2 diabetes and losing weight may help prevent developing diabetes. Although metformin is not an FDA-approved weight loss drug, there is research suggesting metformin treatment may lead to a modest amount of weight loss. Metformin may be prescribed off-label for weight reduction in people at high risk for metabolic complications such as those who have prediabetes. Weight management is important when treating and preventing diabetes to reduce the risk for complications and improve overall health.
In one study, it was determined that metformin can be an effective drug to reduce weight in an outpatient setting in insulin sensitive and insulin resistant overweight and obese patients. The study found an average weight loss in the metformin treated group after 6 months was 5.8 kg (about 12.8 pounds). The observed weight loss in the metformin-treated patients was 10% or more in 16.2% of people and at least 5% in 47.4% of people.
In another study, it was determined that metformin used in overweight or obese individuals with elevated fasting glucose and impaired glucose tolerance was associated with modest but durable weight loss. Additionally, the study determined that metformin therapy was safe and well tolerated over many years. The study initiated those being treated with metformin at a dose of 850 mg once per day and increased the dose within 1 month to 850 mg twice daily unless gastrointestinal symptoms warranted a longer titration period. The study found a mean weight change at 1 year of 2.7 kg (about 6 pounds) in the metformin group. Metformin reduced the development of diabetes by 31% over an average of 2.8 years of follow-up. Weight loss was a strong predictor of diabetes prevention in both the metformin and placebo groups with weight loss accounting for 64% of the metformin versus placebo effect on diabetes prevention. Additionally, metformin produced a highly significant reduction in waist circumference.
How does metformin work for weight loss?
While some diabetes drugs may cause weight gain, the use of metformin is not associated with weight gain. Current evidence suggests that the weight change associated with metformin is more likely to be due to decreased intake of calories versus increases in energy expenditure. Metformin appears to impact appetite regulation both directly and indirectly due to its gastrointestinal side effects.
Additionally, the potential for weight loss with metformin could be a result of lowering blood insulin. High levels of insulin (hyperinsulinemia) can lead to sugar cravings, weight gain, and feeling hungry all the time. By regulating the amount of insulin in the body, people may lower their food intake by experiencing fewer carbohydrate cravings and decreased constant feelings of hunger. Additionally, the hormone leptin that regulates food intake and body mass may play a role in how metformin can cause weight loss.
Metformin also has a beneficial effect on the blood lipid profile, by lowering plasma triglyceride (fats in the blood) and cholesterol concentrations. High triglycerides or cholesterol in the blood can raise the risk of heart disease and stroke.
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Who can take metformin for weight loss?
Metformin may be prescribed off-label for weight loss. Prescribers may be more likely to prescribe metformin for weight loss in people at high risk for metabolic complications such prediabetes, metabolic syndrome, or polycystic ovary syndrome (PCOS). While not FDA-approved for weight loss, metformin has been found to be safe and well tolerated in overweight and obese individuals with elevated fasting glucose and impaired glucose tolerance. In the study, Long-Term Safety, Tolerability, and Weight Loss Associated With Metformin in the Diabetes Prevention Program Outcomes Study, the studied dose was 850 mg once per day with an increased dose within 1 month to 850 mg twice daily unless gastrointestinal symptoms warranted a longer titration period. Prescribers may use a similar dose for off-label weight loss metformin therapy or one of the below doses for different uses.
Metformin dosage for weight loss
|Type 2 Diabetes||-850 to 1000 mg immediate release tablet by mouth twice daily|
-1000 to 2000 mg extended release (ER) tablet by mouth once daily
|*Prevention of Type 2 Diabetes||850 mg tablet by mouth twice daily|
|*Polycystic Ovary Syndrome (PCOS)||-500 mg immediate release tablet by mouth three times daily or 850 to 1000 mg immediate release tablet by mouth twice daily|
-1500 to 2000 mg extended release (ER) tablet by mouth once daily
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Other diabetic medications that cause weight loss
Along with metformin, several other diabetic medications have shown to cause weight loss including GLP-1 receptor agonists, amylin mimetics, and SGLT2 inhibitors. According to the Mayo Clinic, people taking these drugs have seen their blood pressure and cholesterol levels improve. This can often be a desirable effect of these medications for people with Type 2 diabetes.
Diabetic medications that may cause weight loss include:
- GLP-1 receptor agonists
- Adlyxin (lixisenatide)
- Bydureon (exenatide extended release)
- Byetta (exenatide)
- Ozempic (semaglutide)
- Trulicity (dulaglutide)
- Victoza (liraglutide)
- Dual-acting GLP-1 agonist and GIP agonist
- Mounjaro (tirzepatide)
- Amylin mimetics
- Symlin (pramlintide)
- SGLT2 inhibitors
- Farxiga (dapagliflozin)
- Invokana (canagliflozin)
- Jardiance (empagliflozin)
- Steglatro (ertugliflozin)
The drug class called glucagon-like peptide 1 (GLP-1) receptor agonists have shown promising studies for weight loss. Ozempic (semaglutide) works to lower blood sugar in people with Type 2 diabetes and can help the body lose weight. In the SUSTAIN clinical trials, semaglutide consistently demonstrated glycemic control and weight loss in participants with Type 2 diabetes and obesity. Ozempic was found to reduce appetite and food cravings. Additionally, it lowered relative preference for carbs, and fatty, energy-dense foods.
The Semaglutide Treatment Effect in People with Obesity (STEP) program was conducted to study people without diabetes who qualified as either overweight or obese. The study used once-weekly semaglutide dosed at 2.4 mg. The results showed a weight loss of 14.9% from baseline after 68 weeks (about 16 months) of semaglutide paired with lifestyle changes. Specifically, about 70% of participants achieved a weight loss of at least 10%, about 50% achieved a weight loss of at least 15%, and about 33% of participants lost at least 20%. To compare impact, 1 to 3 years after sleeve gastrectomy (a form of bariatric surgery) there is an approximate 20 to 30% weight loss.
Additionally, an oral tablet form of semaglutide, Rybelsus, was approved in 2019. This is the first approved oral GLP-1 receptor agonist and gives people with Type 2 diabetes a non-injectable option. Like Ozempic, Rybelsus currently is only approved for use in people with Type 2 diabetes mellitus to improve blood sugar control. Rybelsus has also demonstrated weight loss in people with an average of 8 pounds lost in a 6-month study.
Like Ozempic, Trulicity (dulaglutide) has shown to cause weight loss but is also not FDA-approved as a weight loss medication. Just as Ozempic has demonstrated, the higher the dose of Trulicity, the more weight loss expected. In Trulicity studies, an average weight loss of 6.6 pounds occurred with the 1.5 mg dose, 8.4 pounds occurred with the 3 mg dose, and about 10 pounds occurred with the 4.5 mg dose. The manufacturer of Trulicity does state that on average, study participants experienced weight loss but some did not lose weight. While Ozempic has shown evidence of slightly greater amounts of average pounds lost, both medications may help people with Type 2 diabetes lose weight.
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How to maximize metformin benefits
- The best time to take metformin is with meals to help lessen the chance of side effects that upset the stomach including nausea, vomiting, abdominal discomfort, and diarrhea.
- It’s advised to not drink a lot of alcoholic drinks while taking metformin. This includes binge drinking for short periods and drinking a lot of alcohol on a regular basis. Alcohol can increase the chance of getting lactic acidosis for those taking metformin. Lactic acidosis is a buildup of lactic acid in the blood, which is a life-threatening medical emergency that requires treatment in the hospital.
- Grapefruits and grapefruit juice can be consumed while taking metformin as there are no known drug interactions. Grapefruit juice has shown some major health benefits as it has a higher content of antioxidant compounds in comparison to other commercial fruit juices. Research has suggested that grapefruit juice can both help fight against insulin resistance and weight gain, which are risk factors for developing Type 2 diabetes.
- Continue regular exercise, a healthy diet, and other lifestyle changes to both achieve and maintain a healthy body weight or BMI (body mass index). For people with diabetes, continue to test blood sugar regularly according to the diabetes care plan established with the healthcare provider.