Can you take glimepiride and metformin together?

In this article:

• Glimepiride vs. metformin
• Can you take glimepiride and metformin together?
• Taking glimepiride and metformin together
• Is glimepiride or metformin better for diabetes?
• Glimepiride vs. metformin: Comparison

In this article

• Glimepiride vs. metformin
• Can you take glimepiride and metformin together?
• Taking glimepiride and metformin together
• Is glimepiride or metformin better for diabetes?
• Glimepiride vs. metformin: Comparison

Metformin and glimepiride are two generic medications that have been approved to treat Type 2 diabetes since 1995. Since Type 2 diabetes is associated with other health risks, such as high blood pressure, heart disease, and stroke, it’s extremely important for diabetes patients to treat their symptoms and high blood sugar before they become worse. Considering the fact that both of these Type 2 diabetes medications have unique benefits, some people may wonder whether it’s advisable to take them together so they can better control their symptoms. Here’s what the experts say. 

Glimepiride vs. metformin: A brief overview

Glimepiride and metformin are both approved to treat Type 2 diabetes, but there are some differences that make these drugs unique. Glimepiride is a sulfonylurea drug that stimulates the pancreas to produce more insulin. It is approved for use in adults, along with diet and exercise, to control blood sugar in people with Type 2 diabetes. Glimepiride is the generic form of the brand-name drug Amaryl.  

Metformin belongs to a class of drugs called biguanides. It works by improving insulin sensitivity and decreasing glucose production. It is FDA approved to treat Type 2 diabetes along with diet and exercise in adults and children 10 years and older, but it also has various off-label uses. Metformin is a generic medication that’s available under the brand names Fortamet, Glucophage, Glumetza, Riomet, and Riomet ER. 

Can you take glimepiride and metformin together?

Logic might suggest that two diabetes medicines can provide double the benefits of one. This isn’t always the case, but for glimepiride and metformin, it can be. “Metformin and glimepiride can be combined for the management of Type 2 diabetes to help lower blood glucose levels,” say Diana Roman, Pharm.D. and Miriam B. Morkos, Pharm.D. of Marshall B. Ketchum University. In fact, a 2019 study demonstrated that this combination therapy is more effective than glimepiride alone, while a study from 2014 showed that it’s more effective than metformin uptitration (the gradual increase of dosage).

That said, it’s not recommended for every patient, specifically those looking to lose weight. “Metformin and glimepiride should not be combined for [the purpose of] weight loss,” Drs. Roman and Morkos say. “Although metformin is considered weight-neutral with the potential for weight loss, glimepiride is associated with weight gain.”

So, in patients whose high blood sugar hasn’t responded to monotherapy, a glimepiride-metformin combination might be a good option—as long as they’re not expecting weight loss. That’s because they work in different ways. Metformin decreases the liver’s glucose production (gluconeogenesis), decreases glucose absorption in the intestines, and increases insulin sensitivity. Glimepiride, on the other hand, works by increasing insulin production in the pancreas. Since they don’t interfere with each other, these actions can work together to effectively manage blood sugar.

Taking glimepiride and metformin together

It’s important to know that you should only take glimepiride and metformin simultaneously if your healthcare provider prescribes them, and it’s crucial to follow the dosage instructions exactly.

The most common dosage for this combination is a 1–2 mg dose of glimepiride with 500–1,000 mg of metformin hydrochloride. Usually, you’ll take glimepiride once daily with breakfast and metformin once or twice a day with meals. And if you forget to take a dose, never make up for it by taking a double dose later; simply take the next scheduled dose as usual.

Your healthcare provider may want to test blood and urine glucose levels throughout glimepiride and metformin combination treatment. As with many diabetes medications, accompanying lifestyle changes—like diet and exercise—can also help manage blood sugar.

Side effects of glimepiride with metformin

Glimepiride belongs to a drug class called sulfonylureas, which can increase the risk of hypoglycemia. “Since glimepiride is a secretagogue that stimulates the release of insulin, it is associated with a risk of hypoglycemia, according to Drs. Roman and Morkos. The risk of hypoglycemia is increased when combined with other diabetes medications.” Therefore, “clinicians should inquire about the occurrence of any hypoglycemic events [in patients] while on glimepiride, and this medication should be used with caution in those with risk for hypoglycemia.”

Other than that, the side effects associated with taking these two together are primarily the same as the side effects of each one individually (see below). In some cases, these overlap and may cause an amplified version of that side effect. Of course, every patient is different, so not everyone experiences the same effects, and some might not experience any at all.

Is glimepiride or metformin better for diabetes?

Both drugs are approved for the treatment of Type 2 diabetes mellitus, and both drugs have been proven effective. But which one is better? Metformin is recommended as a first-line treatment, while glimepiride typically is not. But the answer can sometimes be more complicated than it might initially seem, since the best option for each person depends on various factors.

Drug class

As we’ve established, metformin and glimepiride are from two different drug classes. Metformin is a biguanide, a drug class that decreases glucose production and absorption, while glimepiride is a sulfonylurea, which stimulates insulin production. Some people may respond better to one than the other or have preexisting conditions that prohibit the use of certain drug classes.

On top of that, metformin is sometimes prescribed off-label to treat Type 1 diabetes, while glimepiride is only suitable for Type 2. Healthcare providers make the call on which type of diabetes medication is best for their specific patients.

Side effects

Side effects might make one of these drugs unappealing or even unusable for certain people, so it’s important to review them beforehand. The most common side effects of glimepiride include low blood sugar, weakness, headache, and dizziness. A few of metformin’s most common side effects include diarrhea, nausea, vomiting, flatulence, weakness, indigestion, and abdominal pain.

Contraindications

Side effects may or may not be cause for concern, but people with certain conditions should avoid these drugs entirely. For example, people with a known hypersensitivity to glimepiride shouldn’t take it, nor should people who have diabetic ketoacidosis—a serious medical condition where the body’s insulin level is too low to use glucose effectively.

Similarly, anyone with a hypersensitivity to metformin or metabolic acidosis (including diabetic ketoacidosis) shouldn’t take it. Plus, people who have severe renal dysfunction from kidney disease should avoid it since it may affect renal function. You should check with your prescribing healthcare provider if you are unsure whether you have any of these conditions.

Other warnings and precautions

Some populations could be more susceptible to low blood sugar than others, and those individuals should use glimepiride with caution. This includes older adults and malnourished people, as well as people with kidney problems, liver disease, thyroid disease, and adrenal or pituitary gland dysfunction. The Amaryl (glimepiride) label also says the use of glimepiride might lead to an increased risk of cardiovascular mortality.

Metformin, on the other hand, 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. According to the metformin label, this occurs primarily in patients with severe renal impairment. People who have liver problems, a recent heart attack, severe infections, or other kidney issues should take metformin with caution.

Metformin is typically considered safe to take while pregnant or breastfeeding. Glimepiride is often considered safe for pregnancy but may not be safe with breastfeeding since there’s very little information on how it affects breast milk and breastfed infants.

Price

Neither medication is particularly pricey, although glimepiride might be slightly less expensive. Without insurance coverage, the average out-of-pocket cost for a one-month supply of metformin is around $170, while glimepiride’s average cash price is $22. Glimepiride is commonly used when the cost is a barrier to other more preferred therapies that have proven heart and kidney benefits or protection, according to Dr. Roman and Dr. Markos—even though it isn’t typically a preferred first-choice medication for Type 2 diabetes. 

Bottom line

Glimepiride and metformin are two popular and effective antidiabetic agents commonly prescribed together to help people with diabetes manage their blood glucose. Typically, this combination therapy is recommended in situations when diet, exercise, and monotherapy have not delivered the desired results. However, it’s not effective when used off-label for weight loss since glimepiride can actually cause weight gain. Regardless, the best way to know if glimepiride and metformin will work for you is to see a healthcare provider who’s familiar with your health history and any other medications you may be taking.