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Semaglutide vs. Metformin for Weight Loss: Which is the Better Treatment?

Managing weight by getting active and following a healthy diet plan isn’t always easy, especially with impaired metabolism. That’s why some patients rely on medications to set them up for success in losing weight, like semaglutide and metformin. These medications might both promote weight loss with their effects on the body, but they are still different. You should know their differences if you’re considering seeking this treatment option.

So which is the better treatment between semaglutide and metformin? Between semaglutide and metformin, once-weekly semaglutide medications provide more significant results in weight reduction than metformin. Wegovy (semaglutide) is also used as a weight management solution, while metformin is used only for weight loss as off-label. But patients can combine these medications with the guidance of reliable healthcare providers.

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Is Semaglutide the Same as Metformin?

Semaglutide and metformin may have similar uses, but they’re completely different from each other. Although they cause almost the same effects on the body, they have different methods of action in treating patients with type 2 diabetes and helping non-diabetic patients to lose weight. They have varying pharmacological properties because they don’t have the same drug class.

The differences between semaglutide and metformin are necessary considerations when choosing the best treatment for controlling your body weight. This allows patients to ensure having the safest and most effective treatment possible.

Comparing Semaglutide and Metformin for Weight Loss

woman measuring her waist

Semaglutide and metformin may have similarities in treating patients with type 2 diabetes and controlling their appetite to prevent unexpected weight gain. But they also have stark differences you need to consider when choosing the best treatment option. These differences are the following:

1. What They’re Used for

Semaglutide and metformin are medications usually prescribed for preventing and treating type 2 diabetes, an impairment in regulating insulin for stabilizing blood sugar levels. Semaglutide isn’t advisable for pregnant women, so metformin is preferred for treating gestational diabetes over semaglutide.

Aside from being medications for diabetic patients, semaglutide and metformin may also be used by non-diabetic obese and overweight patients for controlling weight gain. Their biological effects on glycemic control also result in weight reduction. Because of this, healthcare providers prescribe these medications for weight management.

2. Type of Medication

Their drug class is one of the primary differences between semaglutide and metformin because this puts them at entirely varying pharmacological properties, from chemical composition to method of action.

Semaglutide belongs to a drug class called incretin mimetics or GLP-1 receptor agonist. As the term implies, medications under this type of drug mimic your incretin hormones to stimulate insulin release, resulting in blood sugar control. The secondary effects of these drugs cause weight reduction due to slowing down gastric emptying and controlling your appetite and cravings.

On the other hand, metformin is included in a type of drug called biguanide. This oral diabetes medication stimulates insulin sensitivity by controlling glucose production in the liver, resulting in the intestines absorbing smaller amounts of sugar.

Semaglutide medications come in oral form or pills and solutions for subcutaneous injections. It comes in brands such as Wegovy, Ozempic, and Rybelsus. Metformin usually comes in tablets and solutions, both taken via the oral route. The common brands of this diabetes medication are Glucophage, Glucophage XR, Glumetza, Fortamet, and Riomet.

3. Dose

Semaglutide and metformin vary in dose when prescribed to diabetes patients – this variation in dose is also the same for those taking these medications for weight reduction. Their differences in chemical structure and potency will also be factors in determining the proper dose to be given to you. 

Semaglutide for weight loss is usually given to obese and overweight patience in once-weekly subcutaneous injections. Your healthcare provider will start by prescribing a low dose, which will escalate after getting your body accustomed to the drug after a few weeks. Its drug escalation usually goes as follows:

DurationWegovy (semaglutide)
Week 1 to 40.25 mg
Weeks 5 to 80.5 mg
Weeks 9 to 121 mg
Weeks 13 to 161.7 mg
Maintenance Dose2.4 mg

There isn’t an official metformin dose recommendation for weight loss. For off-label uses, your healthcare provider will prescribe the proper dose according to your bodily needs and medical history. But usually, patients will start with these low doses of metformin:

  • Immediate-release type:
    • 500 mg 1 to 2 times a day
    • 850 mg once a day
    • 750 mg to 2000 mg for maintenance dose
  • Extended-release type:
    • 500 mg to 2000 mg for extended-release medications.

Your healthcare provider will adjust your dose according to your body’s response to the medications. They can increase or decrease your dose. They can also delay your dose escalation if your body is having a hard time tolerating the medication’s effects.

4. Mechanism of Action

Semaglutide and metformin come from different classes of drugs, so you can expect them to have varying mechanisms of action in controlling blood sugar levels and promoting weight reduction.

Semaglutide belongs to a class of drugs called incretin mimetic or GLP-1 receptor agonist. This drug promotes glycemic control by mimicking the function of incretin hormones and promoting insulin secretion in the pancreas. 

The incretin hormones are released by the intestines when we eat to communicate to the body the type of nutrients and compounds your body has received from your food. These hormones send signals to the pancreas to monitor glucagon and insulin secretion. 

Receiving GLP-1 RA medications stimulates the beta cells, which contain GLP-1 receptors. The beta cells are responsible for lowering blood glucose levels by releasing insulin, which will prompt the liver and fat and muscle cells to absorb more glucose from the blood. GLP-1 receptor analogs also hinder glucagon secretion.

Metformin is considered one of the first lines of defense for diabetes patients. As a drug belonging to the biguanide class, metformin activates enzymes in the liver responsible for glucose production. Metformin also improves insulin sensitivity, enhancing the liver's glucose absorption. This method of action results in blood sugar control. 

5. Weight Loss Effects

While semaglutide and metformin are medications for treating diabetes patients, their secondary effects in glycemic control have resulted in weight loss, especially among obese and overweight patients with medical conditions. This is because both medications cause the following:

SemaglutideMetformin
Delay in gastric emptying
Reduction of appetite due to signals delivered to the brain
Increase in energy levels
Delay in gastric emptying
Reduction of appetite due to signals delivered to the brain
Improvement in insulin sensitivity
Improvement in fat oxidation from stored glucose

These effects have made semaglutide and metformin some of the treatment options for weight management among obese and overweight patients, even those without diabetes. A brand of semaglutide, Wegovy, has been used as a weight loss medication, while many healthcare providers only use metformin off-label for reducing body weight.

6. Adverse Reactions

Semaglutide and metformin can cause side effects as your body interacts with the drug and causes reactions. These adverse reactions are usually normal responses of the body to the medication. Some of the common side effects are:

SemaglutideMetformin
Nausea
Vomiting
Diarrhea
Constipation
Stomach pain
Hypoglycemia or low blood sugar levels
Reduced appetite
Bloating
Indigestion
Heartburn
Nausea
Diarrhea
Flatulence
Indigestion
Bloating
Heartburn
Constipation

These common side effects should resolve after a few days. Semaglutide and metformin may also cause rare and serious side effects. You might want to consult your doctor if you experience the following symptoms from taking any of these anti-obesity medications to assess your condition and receive proper treatment:

SemaglutideMetformin
Mood changes
Fever
Blurry vision
Depression and anxiety
Irregular heart rate
Dizziness
Hoarse voice
Difficulty swallowing
Stomach pain that reaches the back
Yellow eyes and skin
Lactic acidosis
Vomiting
Muscle pain
Cold feeling
Difficulty breathing
Fatigue
Dizziness
Stomach pain
Irregular heart rate

These are only some of the side effects of semaglutide and metformin. Ensure keeping close coordination with a reputable healthcare provider who can observe your body’s reactions to the medications. This allows them to detect serious side effects immediately and perform the proper treatment.

7. Drug Interactions

Semaglutide and metformin also have drug interactions that may affect your treatment or even exacerbate your existing medical condition or cause side effects. That’s why you should seek a reliable healthcare provider to perform a thorough screening, ensuring that the treatment option is suitable for you. Semaglutide and metformin can react negatively to drugs with:

SemaglutideMetformin
Byetta
Dulaglutide
Exenatide
Insulin
Liraglutide
Trulicity
Victoza
Carbonic anhydrase inhibitors
Cimetidine
Cephalexin
Dolutegravir
Ranolazine
Bupropion
Iodine contrast agents
Glycopyrrolate
Lamotrigine
Topiramate

These are only some of the drug interactions of semaglutide and metformin – there are over 200 medications that interact with these anti-diabetes drugs. Patients taking these medicines are also advised to avoid alcoholic beverages. Consult your healthcare provider to determine if any of the drugs you’re currently taking have counter effects on semaglutide or metformin.

8. Clinical Trials

Semaglutide and metformin come from different drug classes and have varying molecular structures. Because of this, they also have distinct pharmacokinetic profiles, making one weight loss drug more potent or effective than the other. 

On its own, metformin can still produce modest weight reduction. A clinical trial has observed the effects of 2500 mg once-daily metformin on patients with a BMI of ≥27 kg/m(2), treated and untreated for obesity, for 6 months. 

The results have reported a mean weight loss of 5.8±7.0 kg (5.6±6.5%) and 0.8±3.5 kg (0.8±3.7%) for the untreated controls from baseline. According to the study, subjects with severe insulin resistance have experienced a more significant weight reduction than insulin-sensitive patients.

However, semaglutide causes more significant weight loss than metformin, according to numerous studies. A clinical trial has studied the effects of semaglutide on non-diabetic obese patients. 

Patients were assigned to a ratio of 2: 1 with 2.4 mg once-weekly subcutaneous semaglutide injections with lifestyle modifications or placebo. They measured the effects of the weight loss drug with the percentage of the change in body weight and at least 5% weight reduction.

The study has reported a more significant mean body weight reduction of -14.9% from baseline in the group taking semaglutide injections more than the -2.4% from placebo. More patients taking these injections also lost more weight by 5% or more.

But patients seeking the most suitable weight loss solution might not choose between semaglutide and metformin alone – they can combine these weight loss medications because they don’t counter each other's effects.

A study has observed the effects of semaglutide on metformin and other weight loss drugs. It has been reported that semaglutide didn’t pose significant effects on these drugs, even their half-lives. The patients have experienced mild to moderate adverse reactions from the addition of semaglutide. The reported side effects were comparable to reactions during the treatment of semaglutide injections alone.

9. Cost

Semaglutide may produce more significant results in weight reduction, but it’s also more expensive than metformin, even when considering the differences in price based on location, brand, and store. A brand of semaglutide, Ozempic, can cost around $2544 per year on average while metformin only costs $130.

Achieve Your Goal Weight for Overall Wellness with Semaglutide Medications at Dr. V Medical Aesthetics

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Aside from being medications for type 2 diabetes mellitus, semaglutide and metformin are also weight reduction solutions because of their effects in reducing appetite and delaying digestion. Between these two medications, semaglutide produces more significant weight loss than metformin, but metformin tends to be a more affordable option. But patients can also opt to combine these drugs to maximize their effects with a proper treatment plan.

Dr. V Medical Aesthetics is one of the best clinics in Florida for providing a wealth of beauty and wellness treatment options for patients. They also offer semaglutide injections for weight management treatment, with highly-trained professionals to prepare a customized treatment plan for you. Get started in managing your weight today for a healthier and more improved quality of life. Book an appointment to learn more.

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