Combination Therapies

Written by: Matt Zajac | Last reviewed: June 2022 | Last updated: July 2022

A single medicine for type 2 diabetes (T2D) may not lower blood sugar (glucose) levels. So your doctor may suggest a combination therapy. Combination therapies are treatments that have 2 drugs in a single pill or injection. Taking a single drug in a combined dose may be cheaper and easier than taking multiple doses.

Common combination therapies include metformin as 1 of the 2 drugs. Talk to your doctor about benefits and risks of combination therapies. Even if they put you on these therapies, you will still need to eat a healthy diet and exercise regularly.

How do combination therapies work?

Combination therapies lower blood sugar for people with T2D. How they work depends on the 2 drugs they contain. The 2 drugs work in different ways to reduce blood sugar. The combination works better than either drug alone.1,2

Most combination therapies include metformin as 1 of the 2 drugs. Metformin lowers the amount of glucose produced by the liver. Therapies that combine metformin and another drug improve blood sugar levels better than metformin alone.1,2

Single pills are available that combine metformin with:1-3

  • Dipeptidyl peptidase 4 (DPP-4) inhibitors, which increase incretin hormones (that help reduce blood sugar after you eat)
  • Sulfonylureas, which increase the release of insulin
  • Meglitinides, which also increase the release of insulin
  • Selective sodium-glucose transporter 2 (SGLT2) inhibitors, which increase glucose in urine
  • Thiazolidinediones (TZDs), which improve how your body uses insulin

Combinations without metformin are also available. These are helpful for people who cannot take metformin and include:4

  • TZDs with:
    • Sulfonylureas
    • DPP-4 inhibitors
  • SGLT2 inhibitors with:
    • Sulfonylureas
    • DPP-4 inhibitors
    • TZDs

Examples

Most combination therapies contain metformin. For example, therapies that combine metformin with other drugs include:

  • Glyburide (Glucovance®)
  • Glipizide (Metaglip™)
  • Rosiglitazone maleate (Avandamet®)
  • Alogliptin (Kazano)
  • Saxagliptin (Kombiglyze® XR)
  • Sitagliptin (Janumet® and Janumet XR)
  • Linagliptin (Jentadueto® and Jentadueto XR)
  • Canagliflozin (Invokamet® and Invokamet XR)
  • Empagliflozin (Synjardy® and Synjardy XR)
  • Dapagliflozin (Xigduo® XR)
  • Ertugliflozin (Segluromet®)
  • Repaglinide (PrandiMet®)
  • Empagliflozin and linagliptin (Trijardy® XR)

Combination therapies without metformin are also available. Some examples of these are:

  • Pioglitazone and glimepiride (Duetact®)
  • Empagliflozin and linagliptin (Glyxambi®)
  • Pioglitazone and alogliptin (Oseni™)
  • Dapagliflozin and saxagliptin (Qtern®)
  • Insulin glargine and lixisenatide (Soliqua™ 100/33)
  • Insulin degludec and liraglutide injection (Xultophy®)
  • Ertugliflozin and sitagliptin (Steglujan®)

What are possible side effects?

Side effects can vary depending on the specific drugs you are taking. Some possible side effects of therapies that contain metformin are:1,2,4

  • Low blood sugar (hypoglycemia)
  • Gastrointestinal problems, such as:
    • Nausea
    • Vomiting
    • Indigestion
  • Headache
  • High levels of lactic acid (lactic acidosis)

Other side effects depend on the other drug in the combination. For example:1,2

  • DPP-4 inhibitors may cause pancreas inflammation or liver problems.
  • TZDs may cause heart or liver problems.
  • SGLT2 inhibitors may cause ketoacidosis or kidney problems.

These are not all the possible side effects of combination therapies. Talk to your doctor about what to expect when taking combination therapies. You also should call your doctor if you have any changes that concern you when taking combination therapies.

Other things to know

Take combination therapies exactly as your doctor prescribes. You may have to try a few different combinations or doses. Your doctor will monitor the effects of treatment. This can help you find a therapy that works well and causes minimal side effects.

The right combination therapy for you depends on traits that are individual to you. These include:1,2

  • Past effects you had from taking single T2D drugs
  • Risk of side effects
  • Other medical conditions you have
  • Other medicines you take
  • Cost

Before beginning treatment for T2D, tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you take. This includes over-the-counter drugs.

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