Combination Therapy for Type 2 Diabetes

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Most people with type 2 diabetes eventually need multiple medications to help them manage their blood sugar (glucose) levels. Finding the right treatment for your needs can take some time.

Understanding how combination therapy works and who it is best for can help you work with your healthcare provider to find the medication combination that’s right for you.

This article discusses combination therapy for type 2 diabetes—what it is, its benefits, risks, and more.

Someone with diabetes testing their blood sugar levels, with oral medication on hand.

Riccardo Livorni / EyeEm / Getty Images

What Is Combination Therapy?

Combination therapy is when two or more medications treat a condition, such as type 2 diabetes. Treatment for type 2 diabetes likely begins with oral anti-hyperglycemic (glucose-lowering) medication.

If blood glucose monitoring or laboratory blood tests indicate that glucose levels are not effectively managed with a single, oral anti-hyperglycemic medication, your healthcare provider will prescribe additional medication.

When determining the correct combination of diabetic medications, your healthcare provider will consider their effects on other health conditions, if applicable.

Benefits of Combination Therapy for Type 2 Diabetes

Over time, uncontrolled blood glucose levels can cause significant health complications.

When a single medication is insufficient to control blood glucose levels adequately, your healthcare provider will consider combination therapy to prevent long-term complications. Such complications include:

As a chronic and progressive disease, type 2 diabetes often requires treatment changes. Establishing a proactive relationship with your healthcare provider is key to ensuring blood glucose levels are managed effectively and efficiently.

Types of Combination Therapy

Initial (or mono) therapy medication treatment for type 2 diabetes typically includes one of the following oral medications:

  • Metformin: Metformin is often the first medication prescribed. However, there is a rare risk that blood glucose levels can drop too low, causing hypoglycemia (low blood sugar).
  • Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), sodium-glucose cotransporter-2 inhibitors (SGLT2i), or dipeptidyl peptidase 4 inhibitors (DPP-4i): GLP-1RAs such as Ozempic (semaglutide) or Trulicity (dulaglutide), SGLT2is such as Jardiance (empagliflozin) or Farxiga (dapagliflozin), or DPP-4is such as Tradjenta (linagliptin) or Januvia (sitagliptin) might be taken, often in conjunction with metformin, to help control blood glucose levels without the potential risk of hypoglycemia.

Your healthcare provider may prescribe the following medications in conjunction with the oral medications listed above for combination therapy:

  • Thiazolidinediones (TZD): TZD medications, such as Actos (pioglitazone) or Avandia (rosiglitazone), which reduce insulin resistance (when your body doesn't respond properly to insulin). Side effects include weight gain and an increased risk of bone fractures in postmenopausal women and senior men.
  • Insulin-secretagogue/insulin-secretagogue glinides (SU/GLN): These oral medications effectively manage blood glucose levels; however, this medication class has the highest risk of hypoglycemia among non-insulin therapy.
  • Basal insulin: Basal insulin is a single daily dose of insulin (a hormone that helps metabolize food) that provides relatively stable blood glucose management for 24 hours.
  • Mealtime insulin: Mealtime insulin are daily doses of insulin taken just before meals to combat post-meal high glucose levels.

Basal insulin creates a high risk of hypoglycemia, so your healthcare provider will closely monitor your glucose levels to ensure correct dosages when first prescribing it.

Risks of Combination Therapy

Medications that regulate blood glucose levels are generally safe. However, like any medication, there are possible side effects. These include:

  • Low blood glucose levels, known as hypoglycemia
  • Gastrointestinal upset, such as nausea
  • Weight gain
  • Increased risk of fractures, especially in postmenopausal women and senior men

Sometimes, type 2 diabetes medications can interact with other drugs. It is essential to review all of your medications, including over-the-counter (OTC) medications or supplements, with your healthcare provider or pharmacist.

Other Treatment Options

Though many can often manage type 2 diabetes with diet, exercise, and medication, other treatment options are possible. These include:

  • Mounjaro (tirzepatide): Tirzepatide is among the first non-insulin injectable medications; it has demonstrated improved blood sugar control without increasing the risk of hypoglycemia.
  • Artificial pancreas: An artificial pancreas is designed to mimic the functions of a normal pancreas to control blood glucose levels. Components of an artificial pancreas include a continuous glucose monitor and an insulin infusion pump. Together, these can calculate and administer the insulin dosage needed to maintain appropriate blood glucose levels.
  • Weight loss surgery: Obesity can worsen the effects of type 2 diabetes. Bariatric (or weight loss) surgery has proved it can positively affect type 2 diabetes and help stabilize glucose levels to the point that you're no longer affected by it.


Type 2 diabetes is a chronic, progressive disease that sometimes requires medications to control blood glucose levels adequately. Combination therapy for type 2 diabetes involves using two or more medications for treatment.

There are many options for combination therapy, including oral anti-hyperglycemic (glucose-lowering) medications and basal insulin. As with any medication, side effects or drug interactions are possible, so collaborating closely with your healthcare team is essential to ensuring optimal safety.

A Word From Verywell

Managing a chronic and progressive condition like type 2 diabetes can be challenging. It's essential to work closely with your healthcare provider because you may require different treatments at different stages of type 2 diabetes.

Frequently Asked Questions

  • Can you combine metformin with other diabetes drugs?

    If metformin alone does not effectively regulate blood glucose levels, a combination of anti-hyperglycemic medications, such as Avandia (rosiglitazone) or basal insulin, may be prescribed alongside it.

  • What is the most effective treatment for diabetes?

    Type 2 diabetes affects people differently, and treatment options vary depending on other diagnosed health conditions. An appropriate nutrition plan and exercise regimen might be enough for some to manage blood sugar levels effectively. Others may need medication. Work with your healthcare provider to develop a treatment plan that is best for you.

  • Can you combine insulin with other medications for diabetes?

    Multiple studies have shown that prescription insulin is safe to take with other medications. When insulin is combined with other anti-hyperglycemic drugs to help regulate blood glucose levels, there is a risk of hypoglycemia. It is essential to tell your healthcare provider about any medication you are taking and work with them to monitor glucose levels continually.

5 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. American Association of Clinical Endocrinologists. Comprehensive type 2 diabetes management algorithm.

  2. American Diabetes Association. Oral medications: getting it right.

  3. U.S. Food and Drug Administration. FDA approves novel, dual-targeted treatment for type 2 diabetes.

  4. National Institute of Child Health and Human Development. What are the treatments for diabetes?

  5. National Institute of Diabetes and Digestive and Kidney Diseases. Insulin, medicines, & other diabetes treatments.

By Pamela Assid, DNP, RN
Pamela Assid, DNP, RN, is a board-certified nursing specialist with over 25 years of expertise in emergency, pediatric, and leadership roles.