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Metformin Review: The Gold Standard for Diabetes?

Metformin Review: The Gold Standard for Diabetes?


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Read our Editorial Guidelines to learn more about what makes our site the premier resource for online health information.


Read our Editorial Guidelines to learn more about what makes our site the premier resource for online health information.

Disclaimer: None of the information in this article constitutes medical advice, and is just the opinion of the writer(s). We recommend that patients follow their doctor’s guidance in regard to diabetes.

Metformin is a prescription medication which is approved by the Food and Drug Administration (FDA) in the U.S. to treat type 2 diabetes. It’s one of the most commonly-prescribed diabetes medications, and it’s also used off-label to treat obesity. Metformin is the shortened version of the drug name, and the drug is alternatively referred to as metformin hydrochloride or metformin HCL.

Metformin is the name of the generic form of the drug, and there are branded versions such as Glucophage and Glumetza. Since these names all refer to the same active drug ingredient, we’ll use them interchangeably throughout the article.

In this article we’ll review published medical studies on metformin to determine if it’s safe and effective for treating type 2 diabetes. We’ll highlight side effects of the medication, explain whether it’s effective for weight loss, and provide information about foods to avoid while taking metformin.

Does Metformin Work for Diabetes?

Metformin has been extensively studied for its efficacy in reducing blood sugar levels.

A medical review published in the Diabetes, Obesity & Metabolism journal referred to metformin as the “gold standard” for type 2 diabetes treatment. The study authors found that metformin typically results in a decrease in glucose production of around 10-30% over time. This is significant for diabetics.

A clinical trial compared the efficacy of metformin for type 2 diabetes at various doses: 500 milligrams (mg), 1000 mg, 1500 mg, 2000 mg, and 2500 mg. The researchers documented a dose-dependent response. This means that higher doses of the drug tended to have proportionally greater effect on blood sugar reduction.

Metformin reduced HbA1c levels (a marker for blood sugar control) by 0.9% in the lowest-dose group and 2% in the highest-dose group, compared with a control group taking placebo pills. The trial participants taking metformin had blood sugar levels decreasing over time, while the trial participants taking placebo medication had blood sugar levels increasing over time.

A more recent medical review published in 2017 concluded that metformin is still one of the most effective drugs for treating and managing type 2 diabetes, but the study authors noted that metformin doesn’t have as much cardioprotective effect as some newer diabetes medications.

As we highlighted in our recent Victoza reviews article of a newer-generation diabetes drug, that drug not only reduced blood sugar but also reduced blood pressure in hypertensive patients, suggesting a cardioprotective effect as a secondary benefit.

We will conclude from the available research that metformin is effective for treating type 2 diabetes. In all clinical trials and reviews we examined, metformin caused a reduction in blood sugar levels.

Metformin for Prediabetes

Because metformin is one of the most common treatments of diabetes, patients are often curious about whether the drug is also effective for prediabetes, which is defined as blood sugar levels above the healthy range but not yet in the diabetic range. Diabetes is typically defined as blood sugar levels at or above 126 mg per deciliter (dL).

It’s worth noting that the American Diabetes Association recommends metformin for the treatment of prediabetes, but the drug is not approved by the FDA to treat prediabetes.

A meta-study analyzed data from three individual clinical trials to determine whether or not metformin was effective for prediabetes. The researchers found that the drug was effective at both an 850 mg twice-daily dose and a 250 mg twice-daily or three times daily dose. For every 10 prediabetic patients treated with metformin, around 1 of them would be prevented from getting diabetes.

We don’t recommend “off-label” uses of medications, which is a term referring to uses of medications outside of what the FDA has approved those medications for. Metformin is not approved by the FDA for treating diabetes.

We hope that more clinical trials are funded evaluating the safety and efficacy of metformin for prediabetes. If more trials can replicate these results, the FDA will likely consider approving the drug for prediabetes.

Metformin Side Effects

The side effect profile of metformin is relatively mild, compared to most prescription drugs we’ve reviewed on Illuminate Health. Medical research shows the majority of metformin side effects are gut-related: 20% to 30% of patients on metformin experience gastrointestinal side effects such as nausea and vomiting.

Metformin does carry a “black box” warning on its FDA label, which is the most severe type of warning for a prescription medication. It indicates a side effect that may be life-threatening.

In the case of metformin, this black box warning describes a rare but severe side effect called lactic acidosis. When lactic acid builds up in the bloodstream it can cause death, and according to the first review linked in this section, this side effect occurs in around 1 in 30,000 patients. The medical review states that this side effect primarily occurs in diabetic patients with liver and kidney dysfunction.

Even though the risk of lactic acidosis is rare, it seems prudent for diabetic patients with liver and kidney dysfunction to speak with their doctor about potential alternative diabetes medications which don’t confer this risk.

Does Metformin Cause Weight Loss?

Many patients are curious about whether metformin causes weight loss, and whether it’s safe to take for weight loss alone. 

As we detailed in our metformin weight loss article, the medication does cause weight loss in overweight and obese patients at a dosage between 1000 mg/day and 2,550 mg/day. This makes metformin a good option for overweight or obese diabetic patients to speak with their doctor about, because the drug can potentially benefit two separate health conditions.

We don’t recommend metformin for weight loss in patients without type 2 diabetes, as the drug is not FDA-approved for weight loss alone. It also hasn’t been thoroughly studied in non-diabetic patients, so researchers cannot conclude whether it would be effective in non-diabetic overweight or obese patients.

Metformin Real User Review

A popular YouTube review of metformin is published by a channel called "The Hangry Woman" and is a real user's experience on the drug. She shares how she attempts to avoid side effects, and the video appears unsponsored:

Metformin Dosage

As referenced in the section on metformin for diabetes, the drug is prescribed at a wide dosing range.

StatPearls, which is one of the largest free medical databases in the U.S., documents how most adults are prescribed a starting dose of 500 mg once or twice daily, or 850 mg once-daily. A maximum dose of 2000 mg once or twice daily can be prescribed using the extended-release (XR) version of the drug.

Typically, doctors will prescribe diabetic patients a metformin dose on the lower end of the therapeutic range, because this reduces the risk of side effects. If the drug fails to successfully lower blood sugar on the lowest dose, the doctor may slowly increase the dose to test its efficacy.

For both blood sugar and weight loss, metformin appears to be more effective at the higher doses of the therapeutic range than the lowest doses, which would be logically expected.

Foods to Avoid While Taking Metformin 

Metformin’s label does not indicate any specific foods to avoid while using the drug.

That being said, we know that high-glycemic foods like baked goods and white bread cause blood sugar spikes, so it seems logical to avoid such foods while using the drug. Eating a whole foods diet free of any packaged or processed foods should benefit most diabetic patients, but as always it makes sense to speak with a doctor prior to making any significant dietary changes.

A medical review published in 2016 found that diets rich in whole grains, fruits, vegetables, nuts and beans, with moderate-to-low alcohol consumption can improve blood sugar control. This type of diet, combined with metformin, may have greater effects on blood sugar than metformin combined with a Standard American Diet high in processed foods like pizza and burgers.

How Does Metformin Work?

Metformin decreases production of glucose by the body and increases insulin sensitivity. In many type 2 diabetics, insulin sensitivity and metabolism is dysregulated due to years of consumption of inflammatory foods.

Not only does metformin decrease the body’s production of glucose, but it has beneficial downstream effects such as decreased intestinal absorption of glucose and therefore decreased blood levels of glucose.

The same mechanism of action of metformin that is beneficial for type 2 diabetics is likely what’s beneficial for weight loss in overweight and obese diabetics. Insulin dysregulation is associated with weight gain. There’s even a medical term “insulin-associated weight gain.”

By normalizing insulin function, metformin may reduce blood sugar levels and weight.

Metformin 2022 Recall

In January of 2022, the FDA announced a recall of metformin in the U.S. manufactured by a company called Viona Pharmaceuticals Inc. 

The metformin extended-release tablets manufactured by Viona Pharmaceuticals had levels of a compound called N-Nitrosodimethylamine (NDMA) which exceeded federal limits. According to the Environmental Protection Agency (EPA) in the U.S., this compound is both toxic and carcinogenic (potentially cancer-causing).

Since metformin is available from a variety of manufacturers, we would recommend that consumers avoid purchasing metformin from this company in the future, as this recall indicates a potential lack of appropriate quality control measures.

Are There Signs Metformin is Working?

Patients are often curious about whether there are early signs that a drug is working. In the case of metformin, we would not recommend using physical symptoms as signs the drug is working or not working.

Metformin is a diabetes drug, so the only way to test whether or not the drug is working is to regularly get blood levels of glucose checked. Doctors will often require type 2 diabetics to get an at-home blood sugar monitor and test their glucose levels once or even multiple times per day. 

There are no well-established physical symptoms of blood sugar normalization based on medical literature that we can identify. Patients could theoretically experience fewer symptoms of hyperglycemia while on metformin, such as blurred vision and frequent urination, but these symptoms will vary patient-to-patient.

Does Metformin Work for PCOS?

Patients diagnosed with polycystic ovary syndrome (PCOS) are often curious about whether metformin is effective for their condition, given that some medical studies have shown an association between PCOS and insulin dysfunction.

There actually have been medical studies conducted to assess whether metformin is effective for reducing PCOS symptoms.

One medical review published in 2015 examined whether the combination of metformin and lifestyle modifications such as improved diet and exercise routine could improve PCOS. The study authors found that metformin plus lifestyle changes was more effective for weight loss than lifestyle changes alone. Weight gain is often associated with PCOS, so this suggests that metformin may be effective for managing this condition.

Another meta-study, published in the Endocrine journal, found that metformin may be effective for a wider range of therapeutic outcomes in women with PCOS than weight loss alone. In particular, metformin was found to improve live birth rate and ovulation rate when combined with standard PCOS treatments like clomiphene citrate.

We do not recommend using metformin for PCOS as this would be an off-label use, but the early research is promising, and we look forward to seeing more clinical trials conducted establishing the safety and efficacy of metformin as a secondary treatment option for this condition.

Blood Sugar Support Supplement

Cinnamon extract is a dietary supplement that can help support healthy blood sugar levels. We are not suggesting this supplement should be used to treat any disease or medical condition, but we would like to share some clinical research on the effects of cinnamon supplementation and blood sugar.

A medical review published in the Annals of Family Medicine journal found that cinnamon consumption reduced fasting blood sugar levels, reduced total cholesterol levels and reduced triglyceride levels.

A clinical trial from 2006 found that cinnamon extract caused a 10.3% blood sugar reduction in type 2 diabetics, while placebo pills only caused a 3.4% reduction.

For consumers interested in cinnamon extract supplements, we recommend choosing a ceylon cinnamon extract rather than a cassia cinnamon extract, because ceylon cinnamon has negligible levels of a toxin called coumarin that's high in cassia cinnamon. A medical review published in the Nutrition Journal concluded that ceylon cinnamon was safer for this reason.

Illuminate Labs manufactures a ceylon cinnamon extract supplement that's potent (standardized to minimum 8% flavonoids) and is third-party tested to ensure purity and label accuracy. 

Interested consumers can check out Illuminate Labs Ceylon Cinnamon Extract at this link.

Metformin and Alcohol

There is a section on metformin’s FDA label, which we’ve linked to previously, indicating that excessive alcohol use may make the drug more dangerous. The label references excessive alcohol use “acute or chronic,” which suggests that even one night of binge drinking may significantly impact risk.

Metformin use may increase lactate metabolism, and as we referenced in the Side Effects section of this article, lactic acidosis is the most severe potential side effect of metformin.

In the context of this information, we would recommend that diabetic patients with an alcohol use disorder consider speaking with their doctor about alternative medications which may not confer this risk. It’s important for patients to be honest with their doctor about their drinking habits to protect their health. Some patients may consider a once-weekly binge drinking event “normal,” but even this may increase the risk of lactic acidosis while on metformin.

Metformin User Reviews

Metformin has been reviewed over 600 times on Drugs.com, which is a website that allows users of prescription medication to publish reviews of their experience on the drug.

We cannot verify the accuracy or authenticity of any information on this site, but we believe it can still be a valuable resource to patients.

The top review of metformin for type 2 diabetes on Drugs.com is written by a user named “Averageguy50yrsold” who claims that he lost weight and improved his quality of life:

“So far Metformin has been a wonder drug for me. I'm dropping weight, not hungry at all, and my energy levels are up. I'm taking one with each meal. I'm losing 5+ lbs a week and it's all from my stomach fat.”

The top negative review comes from a user named “Ana ruby” who gave the drug a 1/10 rating and claims it caused uncomfortable side effects:

“I was taken metformin for 5 months now and am losing a bit of my weight but one thing my concerned is I'm having diarrhoea all time and the worst part is if I'm going out like for walking or groceries middle of this situations I really need to go toilet straight away otherwise I will be poop on my jeans. This is really disturbing for me”

Does Metformin Cause Diarrhea?

Diarrhea is obviously an uncomfortable side effect of a medication, and patients are often curious about whether metformin causes this side effect given that it can cause gastrointestinal symptoms in some patients.

Unfortunately, metformin does appear to increase the risk of diarrhea.

Metformin has been identified as a potential cause of late-onset diarrhea, which is defined as chronic diarrhea experienced by patients without a medical history of this condition, in a case report. This type of medical research is weaker than larger clinical studies involving many patients.

An animal study helped researchers understand how metformin may cause diarrhea. The researchers found that mice with low levels of a particular bacteria called Firmicutes in their gut were more likely to experience diarrhea, suggesting that the microbiome may predispose human patients to diarrhea while using metformin.

Metformin will not cause diarrhea in all patients, but in light of this information we believe it’s worthwhile for patients to speak honestly with their doctor if they’re experiencing chronic diarrhea while using metformin, because this is not a healthy event to experience regularly.

Metformin Vs. Berberine

Berberine is a dietary supplement which is available over-the-counter (OTC) in the U.S., which means it doesn’t require a doctor’s prescription. It can be purchased online or in various retailers. This compound is derived from a variety of different plants, and has been shown in early research to be effective for diabetic patients.

One clinical trial compared the effectiveness of berberine and metformin in diabetic patients. Trial participants received either 500 mg of berberine three times daily, or 500 mg of metformin three times daily.

The results of this trial are surprising: berberine was as effective as metformin for reducing blood sugar levels, but also had favorable effects on cholesterol levels (like reducing triglycerides), while metformin did not.

These early results don’t prove that berberine is more effective than metformin; much more research would be needed replicating these results to prove that. We do not recommend that patients discontinue metformin in favor of berberine given that there is far less research on the latter compound.

These results do suggest that prediabetic patients may benefit from speaking with their doctor about berberine, given that there are no approved medications for prediabetics and berberine appears to have a potent anti-hyperglycemic effect.

Metformin Alternatives

There are a variety of type 2 diabetes medications available on the market, some of which may be more effective for certain patients than metformin, given that every patient responds differently to prescription medication.

Victoza is a type 2 diabetes medication. This drug was found to be slightly less effective (but not to a statistically significant degree) in a head-to-head clinical trial on diabetic patients. This drug is injectable rather than available as oral tablets like metformin, so it may be a better option for patients with an aversion to pills or an inability to swallow them.

Rybelsus is another diabetes drug that was found to be equivalently effective to metformin in our Rybelsus reviews article. In that article we detailed how the two drugs were actually tested in combination, and found to yield superior results to either drug in isolation. This suggests that patients with difficult-to-treat diabetes may benefit from speaking with their doctor about taking both Rybelsus and metformin.

Overall we have not come across a prescription medication for type 2 diabetes that’s more effective than metformin.

Stay up-to-date on our research reviews

Conclusion

Metformin is effective for treating type 2 diabetes based on a thorough review of medical research. The drug also appears to cause weight loss on average in overweight and obese patients, but we don’t recommend taking it for that purpose alone, given that it’s not FDA-approved for weight loss.

There is favorable early research on metformin for prediabetes and PCOS, and if more research emerges the FDA may consider approving metformin to treat these conditions as well.

A dietary supplement called berberine is as effective as metformin for glucose control at least based on one clinical trial, and may be a good option for patients with prediabetes.

Metformin’s most common side effects are relatively mild, and tend to be gastrointestinal, such as diarrhea and nausea. The more concerning side effect is lactic acidosis which apparently affects around 1 in 30,000 patients. This condition is potentially life-threatening, and its risk seems to increase with alcohol use, so it’s advisable for patients using metformin to avoid alcohol entirely.





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