Metformin and semaglutide are medications primarily used to treat type 2 diabetes. Both drugs effectively lower blood sugar, but they function through different mechanisms and have varying effects on weight loss, administration, side effects, and cost. This article provides a detailed comparison of metformin and semaglutide to help individuals make informed decisions about their treatment options.
Introduction to Metformin
Metformin (Fortamet, Glumetza) has been used to treat diabetes since its approval in 1994, and is often a first-choice treatment for newly diagnosed or mild to moderate cases of diabetes. It lowers the amount of glucose produced by the liver and increases insulin sensitivity. While not FDA-approved for obesity, metformin is sometimes prescribed off-label for weight loss, particularly in individuals with insulin resistance or polycystic ovary syndrome (PCOS).
Introduction to Semaglutide
Semaglutide (Ozempic, Rybelsus) is a newer drug that belongs to the class of GLP-1 (glucagon-like peptide-1) agonists and became available in 2017. Ozempic is the brand name of the injectable form of semaglutide. It mimics the effects of the GLP-1 hormone, stimulating insulin release from the pancreas, slowing down digestion, and signaling the brain to reduce appetite. Semaglutide is particularly beneficial for individuals with diabetes and heart disease, as it lowers the risk of heart attacks and strokes and protects the kidneys. Higher-dose versions of semaglutide, such as Wegovy, are approved for weight loss alone.
How They Work: Mechanisms of Action
Metformin lowers blood sugar by decreasing the amount of glucose produced by the liver and increasing insulin sensitivity, helping cells absorb and use glucose more effectively.
Ozempic mimics the GLP-1 hormone, which is naturally released after eating. It stimulates insulin release from the pancreas when blood sugar is high, reduces glucagon secretion (which raises blood sugar), and slows gastric emptying. This can lead to a feeling of fullness and reduced appetite.
Read also: Berberine and Metformin
Administration Methods
One of the most significant differences between metformin and Ozempic is how they are administered. Metformin is available as a pill or liquid taken daily, typically starting with 500 milligrams at breakfast and dinner, or 850 milligrams at breakfast. The dosage may be increased by a doctor if blood sugar isn’t controlled. There is also an extended-release formula taken once a day with the evening meal.
Ozempic is administered as a once-weekly injection using a disposable push-button pen. The dosage is gradually increased over months, starting with 0.25 milligrams for four weeks, then 0.5 milligrams a week for at least another four weeks, up to a maximum of 2 milligrams each week.
Weight Loss Effects
Although neither metformin nor Ozempic are primarily prescribed for weight loss, both medicines can cause weight loss. Ozempic is typically more effective for weight loss. Research indicates that people with type 2 diabetes and obesity lost an average of 5% to 6% of their body weight after taking Ozempic for a year, compared to a 2% loss for those using metformin after two years. Stronger versions of GLP-1s, such as Wegovy (semaglutide), liraglutide (Saxenda), and tirzepatide (Zepbound), can lead to more significant weight loss, about 10% to 20% of body weight after a year.
Studies show that people taking semaglutide, the active ingredient in Ozempic, lost about 15% of their body weight after 16 months. In contrast, studies show that taking metformin can lead to a 5% to 7% weight loss over several months to a year. The Diabetes Prevention Program (DPP) found that lifestyle changes led to more weight loss than taking metformin alone. The semaglutide in Ozempic tends to produce faster and more significant weight loss, while metformin leads to more gradual changes.
Additional Benefits
Both metformin and Ozempic can help treat the symptoms of polycystic ovary syndrome (PCOS), which often causes insulin resistance and weight gain. Metformin improves insulin sensitivity and is a good option for people with PCOS who don’t need to lose weight. Ozempic lowers blood sugar and leads to significant weight loss. Metformin can lower the risk of developing type 2 diabetes in people with prediabetes when diet and lifestyle changes aren’t enough. Semaglutide lowers the risk of heart attacks and strokes and protects the kidneys in people with diabetes and heart disease.
Read also: Comprehensive Study: Metformin and Phentermine/Topiramate
Side Effects
Metformin and Ozempic have similar side effects, including diarrhea and upset stomach. The side effects of metformin are usually milder and resolve with time or by eating food, while Ozempic’s side effects can be tougher and trickier to treat.
Common side effects of metformin include:
- Stomach pain or upset
- Diarrhea
- Nausea
- Bloating and gas
- Heartburn and indigestion
- Headache
- Metallic taste
Common side effects of Ozempic include:
- Nausea
- Diarrhea
- Constipation
- Throwing up
- Bloating and gas
- Heartburn and indigestion
In rare cases, GLP-1 agonists like Ozempic have been linked with eye problems, gallbladder and pancreas problems, blocked intestines, and stomach paralysis (a condition in which your stomach muscles don't contract as they should to help you digest food). Metformin can lead to a vitamin B12 deficiency, so your doctor should test for that every year.
Cost and Insurance Coverage
Metformin is a generic drug, making it much more affordable than Ozempic. With insurance, metformin tends to cost around $4 a month, and Medicare may cover much or all of the cost. Without insurance, metformin ranges from $4 to $15.
Read also: Health Benefits of Metformin
Ozempic's monthly cost can range from $25 to $200 with insurance, and without insurance, a month's supply can cost $1,000 to $1,400. Because metformin is more likely to be covered by health insurance, it is often a more accessible option for many patients.
Switching Between Medications
Because the drugs work in different ways, Ozempic won't replace metformin entirely, but a doctor may suggest Ozempic if you have heart disease or need to lose weight. If you have severe diabetes, you may need to take metformin and Ozempic at the same time. On the flip side, you may need to switch to metformin if you can't tolerate Ozempic's side effects or if the price is too high.
Long-Term Effects
Doctors have more data about metformin’s long-term effects. It is safe to use in the long run, and research shows taking it for more than six years may even help protect your mental sharpness. Long-term metformin use can lower B12 levels, leading to fatigue, numbness, tingling in the hands and feet, weakness, pale/yellowish skin, and memory issues.
Because Ozempic is a newer drug, scientists are still studying its long-term effects. In rare cases, GLP-1 agonists like Ozempic have been linked with eye problems, gallbladder and pancreas problems, blocked intestines, and stomach paralysis.
Drug Interactions
Ozempic and metformin can interact with other medications. Semaglutide delays gastric emptying, which may affect the absorption of oral medications. Metformin can interact with drugs like cimetidine, diuretics, and contrast dyes used in imaging procedures, elevating the risk of lactic acidosis, especially in individuals with kidney, liver, or heart conditions.
Taking Metformin and Ozempic Together
Yes, you can take metformin and Ozempic together if you have type 2 diabetes. Since they work in different ways, they can complement each other for better results. Metformin improves insulin sensitivity, while semaglutide regulates appetite and improves blood sugar control. However, both medications can cause stomach-related side effects, like nausea, bloating, or diarrhea, especially when starting out.
Research Studies
A prospective, non-randomised cohort study evaluated the efficacy and safety of oral semaglutide for the treatment of antipsychotic-induced weight gain (AIWG). After 16 weeks, the mean body weight loss was 4.5 kg in the semaglutide group versus 2.9 kg in the metformin group. This corresponds to an average body weight loss of 4% for semaglutide and 2.5% for metformin. The differences between the two groups were not statistically significant.
Alternatives to Metformin and Ozempic
If Ozempic or metformin isn’t the right fit due to cost, availability, or personal preference, several alternatives may support weight loss. These include other GLP-1 receptor agonists.
Making the Right Choice
Choosing between Ozempic and metformin for weight loss isn’t just about which one works faster or leads to more pounds lost, it’s about what fits your life. Ozempic tends to deliver more significant weight loss, but it’s also pricier, less likely to be covered by insurance, and requires weekly injections. Metformin, while not quite as powerful for weight loss, is a more affordable option and often a better starting point, especially if you’re dealing with insulin resistance or prediabetes.
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