METFORMIN FOR WEIGHT LOSS

If you were to ask a chemist, they might describe metformin as a “biguanide antihyperglycemic agent.” That really just means that metformin is a drug belonging to the biguanide class that functions as a blood sugar-reducing or stabilizing agent. 

Interestingly, metformin is the only member of its biguanide class currently available in the United States. In Europe, it has been prescribed since the 1950s but in use for far longer: The drug was first discovered as a compound within French lilacs, a plant used in folk medicine for centuries. 

As mentioned previously, metformin is prescribed for individuals who could benefit from tighter glucose regulation and improved insulin sensitivity in order to improve blood sugar control. It is meant to be taken while simultaneously making lifestyle changes, including changes to food and regular exercise. 

Metformin is available as an oral tablet or solution in immediate-release as well as extended-release forms. For some individuals, it may support weight loss, and is a safe and cost-effective option to explore alone or in combination with other agents. 

As a glucose inhibitor, metformin is highly efficient. Meformin works by inhibiting glucose production in the liver. The drug also helps increase the body’s insulin sensitivity (counteracting insulin resistance) and may reduce the amount of glucose absorbed in the bloodstream from food. Summarized, its three primary mechanisms of action are: 

- It decreases hepatic glucose production

- It decreases intestinal glucose absorption

- It increases insulin sensitivity

How, exactly, this happens on a molecular level is poorly understood. Recent studies have sought to uncover more of the mystery and, while we don’t yet know how it suppresses glucose production, other findings have brought renewed attention to the legacy drug:

According to a 2015 study, metformin boasts possible preventive and therapeutic effects on many types of human cancers. The researchers note, “Several biologically plausible mechanisms exist to explain an association between metformin and reduced cancer development and progression. These mechanisms focus largely on inhibiting growth stimuli and metabolic processes within cancer cells.”

For individuals with type-2 diabetes, a 2020 study concluded that metformin treatment may even be an independent protective factor for cancer, including cancers of the breast, colon, and prostate. 

In terms of weight loss, metformin's ability to improve insulin sensitivity is most helpful. Insulin is anabolic, meaning it promotes fat storage. By improving insulin sensitivity, the body is able to control glucose levels with less insulin secretion. Less insulin reduces anabolic signaling and better facilitates lipolysis (the breakdown of fat).

Metformin is not indicated for the treatment of obesity or overweight. However, it is often prescribed alongside other medications (such as GLP-1s) to support weight loss and promote blood sugar control. In addition, clinical studies support the off-label use of metformin for weight loss. These studies have found that metformin is generally most effective in individuals with insulin resistance regardless of a diabetes diagnosis. 

What about taking metformin alone? Can metformin cause weight loss? The often-cited Diabetes Prevention Study (DPP), conducted in 2012, “examined the preventative impacts of metformin on metabolic parameters” in patients considered high-risk for type-2 diabetes.  

Researchers found that metformin reduced the incidence of diabetes in those patients by 31% over a 3-year period. In addition, participants experienced an average 3.5% weight reduction, with more significant weight loss correlating with stronger adherence to the protocol. This is a fairly small percentage, but still meaningful. 

Another 2017 study found that metformin may prevent or mitigate weight gain in patients taking antipsychotic medications (of which weight gain is often a side effect). In these patients, weight gain often leads to poor health outcomes and low self-esteem. Researchers noted that “young, healthy patients beginning olanzapine or clozapine probably will experience less weight gain if they concomitantly initiate metformin.”

Overall, while metformin is infrequently prescribed for weight loss alone, the drug has a strong safety profile and is well-tolerated when used as prescribed. Severe side effects with metformin are rare (see more about side effects below).

Typically, adults prescribed immediate-release metformin for type 2 diabetes will take 500 mg orally twice a day. The dose may then be titrated up in 500 mg increments weekly as tolerated.

After titration, the maintenance dose of immediate-release metformin is 2000 mg/day in divided doses. Divided doses should be taken with meals, typically twice per day (for example, with breakfast and dinner). The maximum dose is 2550 mg/day. 

Extended-release metformin has a slightly different dosing schedule. The initial dose is generally 500 to 1000 mg per day, taken with your evening meal. The dose may be increased by 500 mg weekly as tolerated. The maximum dose of extended-release metformin is 2000 mg/day.

Again, follow your doctor’s instructions when taking metformin, and talk to your doctor if you have any questions or concerns about dosage or timing. Your care plan may vary based on other medications you are taking or preexisting conditions. 

When you join Calibrate, you’ll complete a comprehensive health intake, including blood work, that your Calibrate doctor will carefully review before customizing your treatment plan and prescribing your GLP-1 medication. Calibrate doctors prescribe GLP-1s because research shows they are the safest and most effective medications for weight loss. Calibrate members lose on average 15% of their body weight with treatment plans on GLP-1s—metformin, in comparison, has shown an average of 3-5% weight loss in clinical studies. 

GLP-1s can be safely taken with other common prescription medications—including those for blood pressure, thyroid, and diabetes—and have no contraindications with other prescription or over-the-counter medications. Keep in mind, however, that GLP-1s should be used cautiously and under doctor supervision with certain medications for diabetes such as insulin and sulfonylureas. 

GLP-1 medications currently available to Calibrate members include Wegovy®, Mounjaro™, Ozempic®, Rybelsus®, Saxenda®, and Trulicity®. Calibrate doctors will prescribe whichever medication will work best for you based on your unique needs and health insurance coverage.

The most common side effects of metformin include:

- Abdominal or stomach discomfort

- Diarrhea

- Decreased appetite

- Gas

- Bloating

- Constipation

Taking metformin with food can help reduce or mitigate side effects. Dangerous side effects are very rare, but can include lactic acidosis, allergic reaction, or hypoglycemia. 

Keep in mind that these are not all the possible side effects of metformin. Talk to your health care provider about any side effects of metformin that become bothersome or that don’t go away. 

The medical team can offer recommendations and supportive care for any issues that arise.  If you experience any allergic reaction such as anaphylaxis or shortness of breath, please seek immediate medical care.

Metformin is FDA-approved and is safe when used as prescribed. As with all prescription medications, there are warnings and contraindications to keep in mind prior to starting treatment with metformin.

Contraindications:

Metformin is contraindicated in patients with:

- Severe renal dysfunction, defined as a glomerular filtration rate (GFR) less than 30 ml/min/1.732

- Congestive cardiac failure needing drug treatment

- Hypersensitivity to metformin 

- Acute or chronic metabolic acidosis

- Impaired hepatic function

Warnings & precautions:

Providers will advise patients to limit or discontinue metformin in the following circumstances:

- When patient reaches an age >80 years, until renal dysfunction is ruled out

- With acute myocardial infarction

- During radiological studies involving iodinated contrast

- During surgical procedures

- With excessive alcohol intake

- When patient begins taking contraindicated medications, e.g. topiramate

Here’s what you need to know about metformin at a glance:

- Metformin is a safe and effective, low-cost diabetes medication prescribed to improve blood sugar control

- Metformin has been FDA-approved since 1995 and prescribed since the 1950s.

- Metformin is not specifically a weight loss drug, but studies have found it effective in producing modest weight loss in patients with type-2 diabetes and insulin resistance

- Calibrate doctors prescribe GLP-1 medications, which are the safest and most effective for sustained weight loss, such as Wegovy®, Mounjaro™, and Rybelsus®

- Recent studies have found that metformin may offer protective effects against certain cancers

- Metformin is generally well-tolerated, with few side effects; severe side effects are very rare