Can you take metformin and phentermine together?

Losing weight can be tough. And it can be even tougher for people who have Type 2 diabetes, which can impair weight loss. That’s why it might seem natural to treat both obesity and diabetes simultaneously. For the past half-century, phentermine has been one of the most commonly prescribed weight loss drugs, and metformin has been one of the most popular diabetes medications—and it’s also prescribed off-label for weight reduction.

People who have been diagnosed with obesity and diabetes (or who just want faster results) might be wondering whether they can take them together to encourage weight loss. The answer isn’t so simple. Here’s what the experts say.

Can you take phentermine and metformin together for weight loss?

You can take phentermine and metformin together, but there are limited situations when a healthcare provider would prescribe them together for weight loss.

“While there are no drug-drug interactions between the two agents, the combination of metformin and phentermine is not one of the preferred or alternative agents formally indicated for weight management,” say Diana Roman, Pharm.D. and Miriam B. Morkos, Pharm.D. of Marshall B. Ketchum University.

That means it’s usually only beneficial under close observation and when a person’s obesity is complicated by another condition. “I usually recommend a combination of metformin and phentermine for patients who have a combination of obesity with a body mass index (BMI) of more than 30 or a BMI of 27 with any of the following conditions: Type 2 diabetes, PCOS, or insulin resistance,” says Yoshua Quinones, MD, board-certified internist with Medical Offices of Manhattan and contributor to LabFinder.com. “Metformin will help with the cravings and sugar levels, while phentermine is an appetite suppressant.”

Here’s more on the conditions that may benefit from this combination therapy:

• Type 2 diabetes: It’s often best to treat obesity and Type 2 diabetes at the same time.

  Studies show that obesity can trigger insulin resistance—increasing the risk of developing Type 2 diabetes—while Type 2 diabetes can also contribute to obesity. If a patient has both and hasn’t been able to lose weight with lifestyle changes, both medications might be necessary.

• Polycystic ovary syndrome (PCOS): This is a hormonal condition that affects women, and it can make the cells less responsive to insulin, causing insulin resistance. Studies have connected PCOS to an increased risk of both

  Type 2 diabetes and obesity, so it can be helpful to treat both insulin resistance and weight gain at the same time in patients with PCOS.

• Metabolic syndrome: This is actually a group of conditions, which all can contribute to the development of Type 2 diabetes and cardiovascular disease. They include insulin resistance, high blood pressure (hypertension), obesity, high blood triglycerides, and low HDL cholesterol. Since it’s a multifaceted condition, metabolic syndrome might require a multi-pronged treatment approach.

One case study examined the effects of phentermine, topiramate, metformin, and semaglutide on an adult male with severe obesity and prediabetes. When combined with a lower-calorie diet, the man saw a 32.5% reduction in total body weight. However, the researchers concluded that more research is necessary to evaluate combinations of weight loss medications.

What about dosages?

“To minimize the gastrointestinal side effects, I usually recommend starting with the lowest dose of metformin,” Dr. Quinones says. He says that would be 500 mg once a day combined with 15 mg of phentermine. “If tolerated, we may go up in the dose. Metformin can go all the way to 2,000 mg a day and phentermine up to 37.5 mg per day.”

The recommended dosage of metformin and phentermine can vary depending on the specific person, their conditions, and other circumstances. The most important thing is to always follow your healthcare provider’s exact dosage instructions when taking both medications together.

Taking metformin with phentermine: Side effects and warnings

You’ll notice that each of the conditions listed in the section above is related to insulin resistance and elevated blood glucose. In those cases, it’s technically possible to take both drugs together since they both can lower blood sugar. For people who don’t have one of the specific conditions listed above, however, taking phentermine and metformin together might cause certain side effects.

“Phentermine is a stimulant that releases norepinephrine, a neurotransmitter from the hypothalamus. This release in norepinephrine results in appetite suppression and satiety,” Drs. Roman and Morkos say. This reduced weight and caloric intake may lower blood glucose. At the same time, “Metformin decreases the production of glucose by the liver, a process called gluconeogenesis, and also decreases intestinal absorption of glucose and increases insulin sensitivity.”

For people with otherwise normal glucose, this dual decrease in blood sugar may cause hypoglycemia. Characterized by abnormally low blood sugar, hypoglycemia can cause dizziness, confusion, increased heart rate, shaking, sweating, chills, and anxiety. In extreme cases, it can be life-threatening, leading to seizures, loss of consciousness, disorientation, and blurred vision. That’s why phentermine’s label lists insulin and oral hypoglycemic drugs under its interactions.

For this reason, anyone taking phentermine and metformin should monitor their blood sugar carefully and follow their healthcare provider’s instructions exactly. If you experience any symptoms of hypoglycemia while taking these drugs together, consult your healthcare provider immediately. And always inform your healthcare provider about any other medical conditions you have or other drugs and supplements you’re taking to avoid interactions with phentermine and metformin.

Is metformin or phentermine better for weight loss?

In a roundup of studies examining the effectiveness of various weight loss medications, phentermine patients saw an average 4.4% weight loss over 28 weeks—although doctors might not always prescribe it for that long. Metformin, when prescribed to people without diabetes or prediabetes, only showed an average weight loss of around 2%. That said, there are a few factors that may determine which of these two is better for particular situations.

Drug class

Both drugs might help you lose weight, but only phentermine is approved by the Food and Drug Administration as a weight loss drug. Metformin is only approved for Type 2 diabetes, although some people also lose weight while taking it. Per Drs. Roman and Morkos, “metformin is considered a weight-neutral agent but can cause modest weight loss; thus, metformin may be used ‘off-label’ by some clinicians for weight loss if the more preferred agents are not affordable or not appropriate for a specific patient.”

So for someone who just wants to lose weight, phentermine might be the better choice. But for someone whose obesity stems from Type 2 diabetes, metformin might be more helpful.

Side effects

Phentermine and metformin each have possible adverse effects that might determine whether they’re viable or desirable for certain people. Some of the most common side effects of phentermine are dry mouth, insomnia, headaches, dizziness, and constipation. A few of metformin’s most common side effects include diarrhea, nausea, vomiting, flatulence, weakness, indigestion, and abdominal discomfort.

Contraindications

For certain populations, taking one of these drugs might actually be dangerous, as they each have contraindications. Phentermine’s contraindications include:

• A history of heart disease or heart failure

• Currently taking or have taken a monoamine oxidase inhibitor (MAOI) in the past 14 days

• Hyperthyroidism

• Glaucoma

• Uncontrolled anxiety or agitated state

• A history of drug abuse

• A hypersensitivity to the sympathomimetic amines

• Pregnancy (since weight loss may harm the fetus)

• Breastfeeding (since it’s unclear if phentermine is excreted in human milk)

And patients should not take metformin if they have:

• Severe renal impairment

• Hypersensitivity to metformin

• Acute or chronic metabolic acidosis

Other warnings

Phentermine is classified by the Drug Enforcement Administration as a Schedule IV controlled substance because of its similarity to amphetamines and its risk of dependence and misuse. It’s typically only prescribed short-term.

Plus, “like any other stimulant, phentermine may cause cardiovascular side effects, which include an increase in heart rate, blood pressure, and heart arrhythmia,” Dr. Quinones says. “This is why it’s important to talk to your primary care doctor about risks and benefits.” The drug label also advises against drinking alcohol while taking phentermine and says it may impair the ability to drive or operate machinery.

Metformin, in rare cases, may cause a condition called lactic acidosis, in which the body produces more lactic acid than it can process. In severe cases, this condition can be life-threatening. However, this occurs primarily in patients with severe renal impairment.

Average cost

Neither drug is extremely expensive, but all other things equal, even small differences in price can make one medication more appealing to some. The average out-of-pocket cost of phentermine is $51 for 30, 37.5 mg tablets, while metformin’s average price is $170 for 60, 500 mg tablets.

With free SingleCare coupons, however, you can get a 30-day supply of phentermine for as low as $8, or a 30-day supply of metformin for $4.

Bottom line

Phentermine and metformin are two drugs that can help patients lose weight, although they aren’t always the best combination. For anyone who has obesity coupled with Type 2 diabetes, PCOS, metabolic syndrome, or another condition that causes insulin resistance, healthcare providers might prescribe them together. For others, the combination of phentermine and metformin could cause severe side effects, so you should only take them together when prescribed and monitored by a healthcare provider.

Sources

• Why does type 2 diabetes mellitus impair weight reduction in patients with obesity? A review, Obesity Pillars (2023)

• Why does obesity cause diabetes?, Cell Metabolism (2022)

• Obesity, insulin resistance, and Type 2 diabetes: associations and therapeutic implications, Diabetes, Metabolic Syndrome, and Obesity (2020)

• Diabetes and polycystic ovary syndrome (PCOS), Centers for Disease Control and Prevention (2024)

• Higher risk of type 2 diabetes in young women with polycystic ovary syndrome: A 10-year retrospective cohort study, World Journal of Diabetes (2022)

• Obesity and polycystic ovary syndrome, Obesity Management (2010)

• What is metabolic syndrome?, National Heart, Lung, and Blood Institute

• Weight loss from combination anti-obesity medication regimens can approach that achieved from bariatric surgery, JCEM Case Reports (2023)

• Phentermine patient information, American Association of Clinical Endocrinology (2013)

• Hypoglycemia (low blood sugar), Cleveland Clinic (2023)

• Phentermine label, Teva Pharmaceuticals USA (2012)

• Pharmacologic treatment of overweight and obesity in adults, Endotext (2000)

• Glucophage (metformin) label, Bristol-Myers Squibb Company (2017)

• Phentermine hydrochloride tablet, DailyMed (2018)

• Metformin hydrochloride tablet, DailyMed (2021)

• Lists of scheduling actions, controlled substances, regulated chemicals, Drug Enforcement Administration (2024)

• Metformin: When should we fear lactic acidosis?, International Journal of Molecular Sciences (2022)

• FDA revises warnings regarding use of the diabetes medicine metformin in certain patients with reduced kidney function, Food and Drug Administration (2016)