Is Weight Loss a Side Effect of Metformin?
Medications that are generally prescribed to diabetic patients to help them manage their blood sugar—including Ozempic and Wegovy—have recently been approved by the FDA to help some people lose weight. This has created a buzz and a big demand (so much so that people Type 2 diabetes struggled to get them for a while).
Another diabetes drug that’s generating a lot of attention as a potential weight loss aid? Metformin. Unlike Wegovy and Ozempic, metformin hasn’t been FDA approved for this purpose. Meaning: it’s not a weight loss drug, per se. But some doctors are prescribing it “off-label” to patients who are at risk for developing type 2 diabetes.
“Metformin is a very safe and old medication that has been used for the management of diabetes for years,” says Dina Peralta-Reich, M.D. “We use it for insulin resistance also.”
Are you wondering how metformin might help with weight loss—and whether you should ask your healthcare provider about it? We’re here to answer your Q’s.
What is Metformin?
Metformin is often the first medication prescribed to people with Type 2 diabetes to help lower their glucose (blood sugar) levels.
Metformin is a man-made derivative of a compound found in abundance in the French lilac plant, which has been used for blood sugar control since the Middle Ages. In 1957 it started to be used as an antidiabetic drug; by the ’90s it became a first-line choice to help treat Type 2 diabetes mellitus (1).
About the Experts
Dina Peralta-Reich, M.D., is director of New York Weight Wellness Medicine and a fellow of the Obesity Medicine Association.
Carlo Manzana, M.D., is a family medicine physician with virtual health platform PlushCare. He is a provider in PlushCare’s weight management program.
Metformin For Weight Loss—How Does It Work?
Metformin causes your liver to lower the amount of glucose it makes and releases into your bloodstream. It also appears that it can act via an energy regulator in cells called AMP-activated protein kinase (AMPK), which can lower the amount of glucose in your bloodstream.
Together, these mechanisms of action bolster insulin sensitivity—a good thing, since people with diabetes usually have some level of insulin resistance.
Metformin also slows the absorption of glucose helping to manage blood sugar levels (2).
Researchers are still working to understand how metformin helps with weight loss. But they have some theories.
Promoting insulin sensitivity
Much of your food intake gets converted into glucose. Under normal circumstances, when that glucose enters your bloodstream, cells in your pancreas release insulin. Insulin triggers your cells to gobble up the glucose for energy. When glucose enters your cells and the levels in your bloodstream decrease, it signals your pancreas to stop producing insulin. Excess glucose gets stored in the liver as glycogen or as fat.
For several reasons, your cells can fail to efficiently take up glucose from your blood or store it. This is called insulin resistance. The result: your pancreas pumps out more of the hormone, trying to overcome your increasing glucose levels. If your cells become too resistant to insulin, elevated blood glucose levels will follow, and, over time, can lead to prediabetes and type 2 diabetes.
“Metformin helps promote insulin sensitivity by decreasing the amount of glucose produced by the liver,” Carlo Manzana, M.D. says. “Additionally, it makes the body’s cells more sensitive by increasing the insulin-mediated receptor tyrosine kinase activity.”
Metformin increases insulin sensitivity, reduce insulin resistance, and improves insulin action in type 1 diabetes (3). Metformin may also help put the brakes on your weight gain, which is associated with insulin resistance. And in numerous studies, metformin has improved insulin sensitivity, which can improve insulin resistance. Insulin resistance and obesity have a complex association with each other (4).
Boosting appetite-suppressing hormones
The use of Metformin may lead you to feel less hungry.
Metformin, like Wegovy and Ozempic, appears to increase the secretion of GLP-1, a hormone that helps delay stomach emptying and sends “I’m full” signals to your brain (5). GLP-1 can also have a positive effect on insulin-producing pancreatic cells by increasing insulin secretion and production (6). Evidence suggests that people with obesity may have reduced GLP-1 secretion1 (7). That loss of appetite may lead you to eat less, leading you to reduce your calorie intake.
“Metformin can also cause increased leptin sensitivity, an appetite suppressant hormone, in the brain,” Manzana says (8). Too much leptin can lead to leptin resistance, which may increase hunger and drive you to eat more (9). Metformin’s actions on leptin may help curb hunger.
Changing your gut microbiome
Metformin treatment may alter gut microbiota, in part, by boosting the production of short-chain fatty acids (SCFAs). SCFAs appear to have metabolic health benefits, including increasing evidence that they may make us more insulin sensitive, improve appetite regulation, and more (10, 11).
Battling ‘inflammageing’
Metformin is also being studied as a longevity-promoting drug, because it appears that it may boost mitochondrial function and combat inflammation (12). Mitochondrial dysfunction and low-grade systemic inflammation (inflammageing) are also linked to obesity (13).
How Much Weight Can You Lose on Metformin?
Less than you might expect. “It is important to note that these effects of metformin may vary with every individual and not every person on metformin will experience weight loss,” Manzana says. “People who have the most impactful weight loss are those who accompany the medication with improvements in their diet and exercise.”
A research review found that most people lost more weight than those who took a placebo (14). But weight loss results on metformin vary.
One long term study published in 2019 found that 28.5 percent of those taking metformin lost about 5 percent or less of their body weight during the first year. And those who lost weight on metformin during the first year had the greatest success with weight loss during years 6-15 (15).
An older study found that people with obesity or having higher body fat and taking metformin for six months lost around 12-15 pounds. Those with more severe insulin resistance tended to lose more than those who had insulin sensitivity (16). And a research review of studies with participants where the average age was 60 years or older, found about a 3.5-6 pound weight loss difference in those treated with metformin when compared to those given a placebo (17).
All told, the research suggests a potential 5-15-pound average weight loss with metformin.
How Fast Will You Lose Weight on Metformin?
Based on the above studies, any weight loss with metformin appears to occur over the course of about 6 to 12 months. But people may see some results earlier.
Metformin may help you lose weight and ward off age-related illnesses.
Can People Without Diabetes Take Metformin for Weight Loss?
Some doctors are prescribing metformin off-label to people with prediabetes to help them avoid developing diabetes. Physicians may also prescribe metformin to non-diabetic individuals to help treat obesity and weight gain from taking antipsychotic medications (18).
“There are other indications to start metformin other than diabetes,” Manzana says.
In people with obesity, achieving and maintaining long-term weight loss can be challenging for many reasons, including because of the complex hormone signaling processes at play, even if they exercise and watch their diet. But metformin works best in tandem with lifestyle changes, regular exercise, and improved nutrition (19).
Metformin for Weight Loss Dosage
Metformin is available in different dosages and as an immediate-release and extended-release option. Patients usually start on a lower dose with the potential for an increase over time (19), but you should take the dose your doctor prescribes.
Common Side Effects and Precautions
Like any other drug, there are potential side effects of metformin. The most common are gastrointestinal side effects, including nausea/vomiting and diarrhea (19). You may also experience:
- bloating/gas
- constipation
- headache
- heartburn
- upset stomach
- unpleasant taste in mouth
More serious but rare side effects include anemia or hypoglycemia (low blood sugar). Although extremely rare, lactic acidosis—which can be a medical emergency—may be caused by too much metformin in the body. Lactic acidosis is when the body produces too much lactate or underuses it, causing a pH imbalance. Symptoms of lactic acidosis include the following:
- loss of appetite
- dizziness/lightheadedness
- extreme fatigue or weakness
- fast/slow heart rate
- feeling cold
- muscle aches/pain
- nausea/vomiting
- skin flushing/warmth
- stomach pain
- breathing trouble
- fruity-smelling breath
- confusion
- jaundice
One last caveat: If you take metformin for weight loss, you may need to stay on metformin long term to maintain any results.
The Bottom Line
Weight management is complex, for many reasons, for example, because a host of hormone signaling processes that regulate metabolism and appetite are involved. That’s why anti-diabetes medications like metformin are sometimes used to aid weight loss. Weight loss on metformin tends to be modest, and it occurs slowly over time, but it’s a medication that can be used as a helpful tool in conjunction with a healthy diet and lifestyle habits.
Metformin may help you lose weight and ward off age-related illnesses.
References
1. Bailey, Clifford J. (2017). Metformin: Historical Overview.
2. Rena, Graham, et al. (2017). The Mechanisms of Action of Metformin
3. Beysel, S. et al. (2018). The Effects of Metformin in Type 1 Diabetes Mellitus.
4. Barazzoni, Rocco, et al. (2018). Insulin Resistance in Obesity: An Overview of Fundamental Alterations.
5. Bahne, Emilie, et al. (2018) Metformin-Induced Glucagon-like Peptide-1 Secretion Contributes to the Actions of Metformin in Type 2 Diabetes.
6. Latif, Wafa, et al. (2023). Compare and Contrast the Glucagon-like Peptide-1 Receptor Agonists (GLP1RAS).
7. Lee, Chooi Yeng. (2021). A Combination of Glucagon-like Peptide-1 Receptor Agonist and Dietary Intervention Could Be a Promising Approach for Obesity Treatment.
8. Tang, Xuemei, et al. (2016). Metformin Increases Hepatic Leptin Receptor and Decreases Steatosis in Mice.
9. Barrios-Correa, et al. (2018). Leptin Signaling in the Control of Metabolism and Appetite: Lessons from Animal Models.
10. Mueller, Noel T., et al. (2021). Metformin Affects Gut Microbiome Composition and Function and Circulating Short-Chain Fatty Acids: A Randomized Trial.
11. Blaak, E.E., et al. (2020). Short Chain Fatty Acids in Human Gut and Metabolic Health.
12. Bharath, Leena P., et al. Metformin Enhances Autophagy and Normalizes Mitochondrial Function to Alleviate Aging-Associated Inflammation.
13. Livshits, Gregory, and Alexander Kalinkovich. (2019). Inflammaging as a Common Ground for the Development and Maintenance of Sarcopenia, Obesity, Cardiomyopathy and Dysbiosis.
14. Lentferink, Y. E., et al. (2018). Efficacy of Metformin Treatment with Respect to Weight Reduction in Children and Adults with Obesity: A Systematic Review.
15. Apolzan, John W., et al. (2019). Long-Term Weight Loss with Metformin or Lifestyle Intervention in the Diabetes Prevention Program Outcomes Study.
16. Seifarth, C., et al. (2012). Effectiveness of Metformin on Weight Loss in Non-Diabetic Individuals with Obesity.
17. Solymár, Margit, et al. (2018). Metformin Induces Significant Reduction of Body Weight, Total Cholesterol and LDL Levels in the Elderly – a Meta-Analysis.
18. de Silva, Varuni Asanka, et al (2016). Metformin in Prevention and Treatment of Antipsychotic Induced Weight Gain: A Systematic Review and Meta-Analysis.
19. Fortamet (Metformin Hydrochloride) Dose, Indications, Adverse Effects, Interactions. Prescriber’s Digital Reference. Accessed January 13, 2023.
