Metformin is a popular prescription drug that is used as a first-line treatment for type 2 diabetes. It’s also an active ingredient in two-ingredient combination drugs.
Combination drugs for people with type 2 diabetes frequently integrate metformin along with another drug that acts differently, because doing this allows both drugs to maximize their effectiveness.
This article will investigate the use of metformin combination drugs for type 2 diabetes and will answer some common questions you might have about combination drugs.
What are combination drugs?
Combination drugs are more complex than just being prescribed two separate pills at once.
Rather, combination drugs integrate two different active ingredients into a single prescription drug. Each of the two (or more) drugs has a unique mechanism of action, meaning it has its own set of effects on the body.
Combination drugs may be approved for use for several reasons, including that there may be a synergistic effect – meaning that the effect of the two drugs when combined is better than it would be if the two drugs were taken separately.
Combination drugs may also be easier for patients to keep track of, because the number of pills you have to take is reduced, and each pill does not have its own requirements for a person to keep track of.
Combination drugs, officially known by the FDA as “fixed-dose combination drugs” (or FDCs), first began coming to market in significant numbers in the 1980s in the United States and truly accelerated in popularity through the mid-1990s.
What is the best combination with metformin?
Just by itself, metformin comes in many brands and is taken daily as an oral pill, generally once or twice each day. Metformin helps you to manage your blood sugar levels, and fight insulin resistance, and it can even help you to lose weight.
However, metformin is not always sufficiently effective on its own. In these cases, a doctor or medical provider may recommend adding a second medication to the treatment regimen.
These are often in the form of fixed-dose combination drugs.
Doctors use many factors when assessing which metformin combination drug will best help in the management of type 2 diabetes. It may also be necessary to try more than one combination drug before finding one that best meets your blood sugar and other health goals while minimizing side effects.
Metformin combination drugs that include SGLT-2 inhibitors are both commonly prescribed and have a strong evidence base.
These combination drugs, which include empagliflozin (brand names: Synjardy or Jardiamet), dapagliflozin (Xigduo XR), and ertugliflozin (Segluromet), work by helping your kidneys to excrete more glucose through the urine, which reduces your overall blood sugar levels.
These combination drugs have been shown to have an HbA1c reduction superior to the use of metformin alone and a clinical trial of over 600 patients with type 2 diabetes also indicated some in this class of combination drugs reduce the risk of heart attack and other serious cardiovascular incidents when compared to taking metformin by itself.
Other effective, though less common, combination drugs that have been shown to be highly effective in decreasing HbA1C levels are “triple combination therapies” with metformin, a DPP-4 inhibitor, and a sulfonylurea agent.
Small-scale trials with this triple combination drug yielded significant A1C improvements, but subsequent triple combination trials with other active ingredients have shown broader effectiveness for larger groups of people with type 2 diabetes.
In large-scale trials, triple combination drugs like Trijardy (which combines empagliflozin, linagliptin, and metformin) have been shown to improve A1C by more than 1.1% compared to taking metformin alone.
It is important to note that while triple combination drugs (or any other kind of combination drug) can be an effective way to help manage blood sugar levels, they aren’t right for everyone.
A doctor or other medical provider will evaluate if these drugs are appropriate for you and if the benefits outweigh any of the potential side effects.
Which antidiabetic drugs can be taken in combination with metformin?
There is a difference between what drugs can be taken at the same time as metformin and what drugs can be taken as a combination drug with metformin.
Metformin is generally well-tolerated and can be taken with a number of other drugs if prescribed by your doctor. It’s always a good idea to tell your medical care team what prescription drugs you are taking to make sure there are no unexpected interactions.
Though plenty of other drugs can be taken at the same time as metformin, there are only a handful of metformin combination drugs that have been approved.
FDA-approved metformin combination drugs include:
- ActoPlus Met (metformin and pioglitazone)
- Avandamet (metformin and rosiglitazone)
- Glucovance (metformin and glyburide)
- Invokamet (metformin and canagliflozin)
- Janumet (metformin and sitagliptin)
- Jentadueto (metformin and linagliptin)
- Kazano (metformin and alogliptin)
- Kombiglyze XR* (metformin and saxagliptin)
- Metaglip (metformin and glipizide)
- PrandiMet (metformin and repaglinide)
- Segluromet (metformin and ertugliflozin)
- Synjardy (metformin and empagliflozin)
- Xigduo XR (metformin and dapagliflozin)
- Trijardy XR (empagliflozin, linagliptin, and metformin)
* All the drugs listed above with “XR” include an extended-release formulation of metformin, which many people find helps to avoid gastrointestinal side effects and sensitivity that is common, even with metformin alone.
What’s next if metformin isn’t enough to manage type 2 diabetes?
It can be discouraging if your blood sugar levels remain elevated even after taking metformin and making dietary and lifestyle changes.
Many people with type 2 diabetes wonder what options they have left if their blood sugar is out-of-range even while taking metformin, or if it feels like metformin is losing its effectiveness over time.
Learn more: Signs Metformin Is Working (Or Isn’t Working).
As discussed in the sections above, oftentimes a doctor will prescribe a metformin combination drug to improve blood sugar control.
Because these drugs have different active ingredients and different mechanisms of action, they often have “synergistic” effects, bringing down your blood sugar more than metformin would alone.
Combination drugs are also considered to be the best next step after metformin therapy because their side effects are well understood and tend to be less serious than other drugs.
A doctor may also consider beginning insulin therapy in conjunction with Metformin.
Synthetic insulin is usually taken as an injection to supplement your body’s own insulin that’s produced by the pancreas. Insulin comes in many formulations, which broadly include rapid-acting (bolus insulin) and long-acting (basal insulin).
In type 2 diabetes, insulin therapy tends to help lower blood sugar levels more quickly than other medications, but it requires careful management and can come with significant side effects, like serious low blood sugar (hypoglycemia), if you take too much insulin at once.
If your average blood sugar levels (as measured by an HbA1c test or long-term use of a continuous glucose monitor) don’t come down, and if you’re already taking the maximum recommended dose of metformin or a combination drug, then your doctor may consider insulin therapy.
If metformin alone just isn’t enough to manage blood sugar, it’s important to talk with a doctor about other options. Everyone’s needs, response to prescription drugs, and overall medical history are different, so discussing the pros and cons of different types of treatment with your doctor is a great place to start.
Learn more: The Best Alternatives to Metformin for Type 2 Diabetes Management.
Frequently asked questions
Combination drugs come in a single pill and are prescribed under a single prescription. They have been tested together and the doses of the two (or more) active ingredients have been calibrated to work together.
A combination drug combines two or more active ingredients into a single pill or dose. Combination therapy uses two or more different drugs to treat a condition and it can also involve taking multiple medications in different ways (e.g., daily metformin pill, plus injectable Ozempic or insulin).
Combination therapy can also involve the use of medical devices, like insulin pumps.
Because combination drugs have fixed ratios of their active ingredients, it may be more difficult to adjust the dosages than if you were taking metformin and the other drug as two separate pills.
Finally, because each active ingredient also has its own potential side effects, increasing the number of active ingredients in a prescription drug often can increase the number of unwanted side effects.
Pharmacists and doctors generally advise that metformin is the safest (and among the most studied) drug for helping blood sugar management for people with type 2 diabetes. However, many metformin combination drugs also have excellent safety profiles.
Nonetheless, it’s always important to discuss treatment options with your doctor to get individualized guidance.
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