Metformin is a popular prescription drug that is used as a first-line treatment for type 2 diabetes. It is also the active ingredient in combination drugs.
Combination medicines for people with type 2 diabetes often combine metformin with another medicine that works differently, as this allows you to maximize the effectiveness of both medicines.
In this article, we will examine the use of combination drugs with metformin in the treatment of type 2 diabetes and answer some frequently asked questions about combination drugs.
What are combination drugs?
Combination medications are more complex than just prescribing two separate pills at once.
On the contrary, combination drugs combine two different active ingredients into one prescription drug. Each of the two (or more) drugs has a unique mechanism of action, which means it has its own set of effects on the body.
Combination medicines may be approved for several reasons, including a synergistic effect – meaning that the effect of the two medicines in combination is better than when the two medicines are taken alone.
Combination drugs can also be easier for patients to track because the number of pills that need to be taken is reduced and each pill does not have its own requirements that a person has to keep track of.
Combination drugs, officially known by the FDA as “fixed-dose combination drugs” (or FDCs), first began to appear on the market in significant numbers in the 1980s in the United States and really took off in the mid-1990s.
What is the best combination with metformin?
Metformin itself comes in many brands and is taken daily as an oral pill, usually once or twice a day. Metformin helps control blood sugar levels and fight insulin resistance, and may even help with weight loss.
However, metformin alone is not always effective enough. In these cases, your doctor or health care professional may recommend adding a second drug to your treatment regimen.
They are often in the form of fixed-dose combination drugs.
Doctors consider many factors when evaluating which combination medicine with metformin will best help treat type 2 diabetes. It may also be necessary to try more than one combination medicine before finding one that best suits your blood sugar and other health goals while minimizing side effects.
Combination drugs with metformin that contain SGLT-2 inhibitors are widely prescribed and have a solid evidence base.
These combination drugs, which include empagliflozin (trade names: Synjardy or Jardiamet), dapagliflozin (Xigduo XR), and ertugliflozin (Segluromet), work by helping the kidneys excrete more glucose in the urine, which lowers overall blood sugar levels.
These combination medicines have been shown to reduce HbA1c better than metformin alone, and a clinical trial involving over 600 patients with type 2 diabetes has also shown that some of this class of combination medicines reduce the risk of heart attack and other serious cardiovascular events compared to taking metformin alone.
Other effective, though less common, combination drugs that have been shown to be highly effective in lowering HbA1C levels are the ‘triple combination therapies’ of metformin, a DPP-4 inhibitor and a sulfonylurea.
Small-scale trials with this triple combination drug showed significant improvements in HbA1c, but subsequent trials of the triple combination with other active ingredients have shown wider efficacy in larger groups of people with type 2 diabetes.
In large-scale studies, triple combination drugs such as Trijards (which combines empagliflozin, linagliptin and metformin) have been shown to improve HbA1C by more than 1.1% compared to taking metformin alone.
It is important to note that while triple combination drugs (or any other combination drug) can be an effective way to help control blood sugar, they are not suitable for everyone.
Your doctor or other health care provider will assess whether these medications are appropriate for you and whether the benefits outweigh any potential side effects.
What diabetes medicines can be taken in combination with metformin?
There is a difference between drugs can be taken at the same time like metformin and what drugs you can take combination medicine with metformin.
Metformin is generally well tolerated and can be taken with many other medications if directed by your doctor. It’s always a good idea to tell your medical team what prescription medications you’re taking to make sure there are no unexpected interactions.
While many other medications can be taken at the same time as metformin, there are only a few approved medications that are combined with metformin.
FDA-approved combination drugs with metformin 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)
- Trijards XR (empagliflozin, linagliptin and metformin)
* The drugs listed above with “XR” all contain an extended-release formulation of metformin, which many people believe helps avoid the gastrointestinal side effects and hypersensitivity that are common, even with metformin alone.
What next if metformin is not enough to treat type 2 diabetes?
Elevated blood sugar levels can be discouraging even after taking metformin and making changes to your diet and lifestyle.
Many people with type 2 diabetes wonder what their options are if their blood sugar is out of range even when taking metformin, or if metformin seems to lose its effectiveness over time.
Learn more: Signs Metformin Is Working (or Not Working).
As discussed in the sections above, often your doctor will prescribe a combination medicine with metformin to help improve blood sugar control.
Because these drugs have different active ingredients and different mechanisms of action, they often have a “synergistic” effect, lowering blood sugar more than metformin alone.
Combination drugs are also considered the best next step after metformin therapy because their side effects are well understood and appear to be less serious than other drugs.
Your doctor may also consider starting insulin therapy in combination with metformin.
Synthetic insulin is usually taken as an injection to supplement the body’s own insulin produced by the pancreas. Insulin comes in many formulations, which include fast-acting (bolus insulin) and long-acting (basal insulin).
For type 2 diabetes, insulin therapy usually helps lower blood sugar more quickly than other medications, but needs careful management and can have significant side effects, such as severe low blood sugar (hypoglycemia) if you take too much insulin for a day. once .
If your average blood sugar level (measured by HbA1c test or long-term use of a continuous glucometer) does not fall and you are already taking the maximum recommended dose of metformin or a combination medicine, your doctor may consider insulin therapy.
If metformin alone isn’t enough to control your blood sugar, it’s important to talk to your doctor about other options. Everyone’s needs, response to prescription medications, 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 treating type 2 diabetes.
Frequently asked questions
Combination drugs are available in one tablet and are prescribed on a single prescription basis. They have been tested together and doses of two (or more) active ingredients have been calibrated to work together.
A combination drug combines two or more active ingredients into one tablet or dose. Combination therapy uses two or more different drugs to treat the condition and may also involve taking multiple drugs in different ways (e.g. a daily metformin pill and Ozempic or injectable insulin).
Combination therapy may also include the use of medical devices such as insulin pumps.
Because combination medicines have fixed proportions of active ingredients, adjusting doses can be more difficult than when taking metformin and the other medicine as two separate tablets.
Finally, since each active ingredient also has its potential side effects, increasing the number of active ingredients in a prescription drug can often increase the number of unwanted side effects.
Pharmacists and doctors generally advise that metformin is the safest (and one of the most studied) drugs to help control blood sugar levels in people with type 2 diabetes. However, many combination drugs with metformin also have excellent safety profiles.
Nevertheless, it is always important to discuss treatment options with your doctor for individualized guidance.
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