For individuals managing type 2 diabetes or seeking effective weight loss strategies, metformin and Wegovy have emerged as potential treatment options. Both are prescription medications that have demonstrated benefits in regulating blood sugar levels and promoting weight loss. While they share similar benefits, it's important to understand that they contain different active ingredients and work through distinct mechanisms.
Understanding Metformin
Metformin is an established medication primarily used to treat type 2 diabetes. It belongs to the biguanide class of drugs and is available as a generic medication under various brand names such as Glucophage, Fortamet, and Riomet. Metformin improves how the body responds to insulin. It is also sometimes used off-label for managing symptoms of polycystic ovary syndrome (PCOS), such as insulin resistance and irregular menstrual cycles.
How Metformin Works
Metformin's primary mechanism of action involves enhancing the body's response to insulin, a hormone that helps regulate blood sugar levels. By improving insulin sensitivity, metformin enables cells to utilize glucose more effectively, leading to lower blood sugar levels.
Administration and Dosage
Metformin is typically administered orally in pill form. It is often taken twice daily, although extended-release versions are available that can be taken once daily. The typical dosage for regular immediate-release tablets is 500 milligrams (mg) twice daily or 850 mg once daily with meals.
Understanding Wegovy
Wegovy is a relatively new brand-name drug manufactured by Novo Nordisk and approved by the Food and Drug Administration (FDA) in 2021. It contains the active ingredient semaglutide and is classified as a glucagon-like peptide-1 (GLP-1) receptor agonist. It’s approved by the Food and Drug Administration for weight management in people with obesity or who are overweight. It’s also approved for the prevention of cardiac events such as heart attack and stroke. The active ingredient in Wegovy is available under a different brand name, Ozempic, which is approved to treat Type 2 diabetes.
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How Wegovy Works
Wegovy mimics the effects of GLP-1, a natural hormone that regulates appetite and food intake. By activating GLP-1 receptors in the brain, Wegovy helps to reduce hunger, increase feelings of fullness, and ultimately, promote weight loss. It also delays gastric emptying partly due to a central action mediated via the autonomous nervous system.
Administration and Dosage
Wegovy is administered as a weekly injection under the skin (subcutaneously). The starting dose is 0.25 mg once weekly for four weeks. It then gradually increases to a target dosage of 2.4 or 1.7 mg once weekly.
Comparing Metformin and Wegovy
While both metformin and Wegovy can contribute to weight loss and improved blood sugar control, they have distinct characteristics that set them apart.
FDA Approval and Uses
Metformin is approved to manage blood sugar levels in adults and children with Type 2 diabetes. Wegovy is FDA-approved for weight management in adults and children with obesity. It is also approved for adults who are overweight with at least one weight-related health condition, such as high blood pressure, diabetes, or high cholesterol.
Weight Loss Effects
Clinical trials have demonstrated that both metformin and Wegovy can lead to weight loss, although Wegovy generally exhibits more pronounced effects. In a clinical trial called the STEP 2 trial, people with Type 2 diabetes and obesity lost an average of 9.6% of their body weight using semaglutide 2.4 mg, compared to just 3.4% with a placebo over 68 weeks. Some studies have shown that metformin can support weight management, though the effects are generally more modest than Wegovy’s. In a study involving people with prediabetes, participants taking metformin lost an average of 4.6 pounds (2.1 kg) within three years. Over time, they maintained an average weight loss of 5.5 pounds (2.5 kg).
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Cost and Availability
As a brand-name drug, Wegovy is generally more expensive than metformin and less likely to be covered by insurance plans. Currently, no generic version of Wegovy is available. Some insurance plans may cover Wegovy if it’s prescribed to reduce heart disease-related risks in people who are overweight with heart disease or have obesity and heart disease. Unlike Wegovy, metformin is a generic drug that is covered by most, if not all, commercial insurance and Medicare plans.
Side Effects
Wegovy and metformin share several common side effects, especially gastrointestinal ones. Both Wegovy and metformin are known to cause nausea, vomiting, diarrhea, constipation, and indigestion. Metformin can cause taste disturbances, diarrhea, and other stomach-related side effects are common side effects. Both medications can cause serious side effects that can differ. For example, metformin has specific serious side effects like lactic acidosis, a rare but dangerous build-up of lactic acid in the blood.
Drug Interactions
Wegovy and metformin have unique and overlapping drug interactions. Taking Wegovy or metformin with insulin or insulin secretagogues, such as sulfonylureas, may increase the risk of low blood sugar (hypoglycemia). When metformin is taken with carbonic anhydrase inhibitors, it can increase the risk of a dangerous condition called lactic acidosis.
Potential Risks and Precautions
Both Wegovy and metformin carry potential risks and precautions that should be considered before starting treatment.
Low Blood Sugar (Hypoglycemia)
Both Wegovy and metformin carry a risk of low blood sugar levels, especially when used with insulin or insulin-boosting drugs.
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Wegovy-Specific Risks
- Thyroid cancer risk: Animal studies suggest Wegovy may cause thyroid tumors.
- Pancreatitis: Wegovy can cause inflammation of the pancreas.
- Gallbladder problems: Wegovy can cause issues with the gallbladder.
- Kidney injury: Wegovy can cause kidney problems.
- Eye problems: Wegovy can worsen diabetic eye disease.
Metformin-Specific Risks
- Lactic acidosis: Metformin can cause a serious condition called lactic acidosis, especially in people with kidney or liver problems or those who drink heavily.
Allergic Reactions
Allergic reactions are possible with both Wegovy and metformin.
Combining Metformin and Wegovy
In some cases, healthcare providers may recommend combining metformin and Wegovy to achieve more comprehensive blood sugar control and weight loss.
Is it Safe to Take Wegovy and Metformin Together?
Yes, you can take Wegovy and metformin together. No research has found a significant difference between the safety or effectiveness of the oral and injectable forms of semaglutide. Because they are completely different classes of drugs, metformin and Wegovy don’t interact with one another.
Potential Benefits
Using these two drugs together can help you achieve multiple goals: losing weight, improving your blood glucose levels, and decreasing your risk of cardiovascular events.
Potential Risks
You should also be aware that taking Wegovy and metformin could increase your risk of side effects. Metformin can cause nausea, diarrhea, and upset stomach; Wegovy can cause nausea, vomiting, loss of appetite, and abdominal pain. Taking them both together may further raise your risk of gastrointestinal (GI) distress. Because both medications lower your blood sugar, there’s also the possibility of hypoglycemia, excessively low blood sugar, according to Dr. Mattingly.
Metformin and Liraglutide Combination Therapy for PCOS
Studies have investigated the combined use of metformin with liraglutide, another GLP-1 receptor agonist similar to semaglutide (the active ingredient in Wegovy), in women with PCOS.
Study Design and Results
A study involving 40 obese women with PCOS who had been pretreated with metformin for at least 6 months, participated in a 12-week open-label, prospective study. They were randomized to one of three treatment arms: metformin (MET) arm 1000 mg BID, liraglutide (LIRA) arm 1.2 mg QD s.c., or combined MET 1000 mg BID and LIRA (COMBI) 1.2 mg QD s.c. Lifestyle intervention was not actively promoted. Thirty six patients (aged 31.3±7.1 years, BMI 37.1±4.6 kg/m2) completed the study: 14 on MET, 11 on LIRA, and 11 on combined treatment. The study found that combined liraglutide and metformin therapy was superior to liraglutide and metformin monotherapy in reducing weight, BMI, and waist circumference. Subjects treated with COMBI lost on average 6.5±2.8 kg compared with a 3.8±3.7 kg loss in the LIRA group and a 1.2±1.4 kg loss in the MET group (P<0.001).
Implications
These findings suggest that combining metformin with a GLP-1 receptor agonist may offer a more effective approach to weight loss and metabolic improvement in women with PCOS compared to metformin alone.
Real-World Experience and Considerations
Rapid Weight Loss and Maintenance
The hype around the newest FDA-approved weight loss injections is well-founded. Semaglutide is prescribed as a weekly shot, and in the first three months, the dosage is minimal. Our patients are instructed to follow a Mediterranean diet consisting of nonprocessed foods, fruits, and vegetables, nuts, legumes, poultry, and fish. Our employees who opted for the program have seen an average of 25 lbs of weight loss in the first three months of semaglutide. After that they discontinue the semaglutide and are put on metformin. But two things differ from what our staff (and patients) are doing vs the clinical trials. The second is the use of metformin (oral pill daily), that is safe and synergistic with semaglutide.
Supply Chain Issues and Generic Versions
At the time of this publication, the Wegovy® brand of semaglutide is having supply chain issues and not readily available. This has led to lack of FDA protection, and it is being produced as a generic compounded version at a fraction of the cost. The FDA allows for pharmacists to use generic sources when a commercial product isn’t available for consumers.