Type 2 Diabetes

Metformin & Oral Meds

What they do, how to take them, and more

Things to know about metformin

  • TIP 1
    Reducing your risk of side effects
  • TIP 2
    What to avoid when taking metformin
  • TIP 3
    How to take metformin
How different oral medications for type 2 diabetes work
To understand why your doctor might prescribe one oral medication over another, it’s helpful to know what they do in the body, along with any side effects they may have.

    Some types of type 2 diabetes medications stimulate the beta cells in the pancreas to release insulin. 

    Meglitinides are taken before each meal to help lower your blood sugar after you eat. Common meglitinides are:

    • repaglinide (Prandin) 
    • nateglinide (Starlix)

    Sulfonylureas are typically taken once or twice a day before meals to help lower blood sugar. Examples include:

    • glyburide (Micronase, Glynase, Diabeta)
    • glimepiride (Amaryl)
    • glipizide (Glucotrol)

    The most common side effects of these medications are hypoglycemia and weight gain.

    DPP-4 inhibitors help lower blood sugar levels only when they’re elevated. They do this by blocking the action of an enzyme called dipeptidyl peptidase-4 (DPP-4). 

    This enzyme breaks down hormones that reduce blood sugar levels. By interfering with this process, DPP-4 inhibitors allow these hormones to remain active in the body for a longer period of time, lowering blood sugar.

    Examples of DPP-4 inhibitors include: 

    • sitagliptin (Januvia)
    • saxagliptin (Onglyza)
    • linagliptin (Tradjenta)
    • alogliptin (Nesina)

    DPP-4 inhibitors are taken once a day, before or after meals. They’re generally well-tolerated and don’t cause hypoglycemia when taken alone or with metformin. (DPP-4 inhibitors also limit the ability of the liver to release glucose. See below.)

    GLP-1 agonists stimulate the body to produce more insulin when blood sugar levels start to rise after you eat. This helps lower blood sugar. 

    Most GLP-1 agonists are taken as a shot. Oral semaglutide (Rybelsus) is currently the only oral option. It’s taken once a day on an empty stomach.

    The liver both stores and produces glucose. Some type 2 diabetes medications limit the liver’s ability to release glucose, helping to lower blood sugar levels.

    Biguanides are taken twice a day. Metformin (Glucophage) is the only medication in this class and is often used as a first-line treatment for type 2 diabetes. Metformin may cause diarrhea, but you can reduce this risk by taking it with food. (Metformin also improves insulin sensitivity. See below.)

    Thiazolidinediones are taken once a day with or without food. Pioglitazone (Actos) is an example of a thiazolidinedione. 

    Thiazolidinediones may increase the risk of heart problems in some people. You should speak with your doctor about whether these medications are safe for you. (Thiazolidinediones also improve insulin sensitivity. See below.)

    DPP-4 inhibitors are taken once a day, before or after meals. Examples include:

    • sitagliptin (Januvia)
    • saxagliptin (Onglyza)
    • linagliptin (Tradjenta)
    • alogliptin (Nesina)

    DPP-4s are typically safe and don’t cause hypoglycemia when taken alone or with metformin.

    GLP-1 agonists are most commonly taken as shots. Oral semaglutide (Rybelsus) is currently the only oral option. It should be taken once a day on an empty stomach.

    Some type 2 diabetes medications make your body more sensitive to the effects of insulin. This allows more glucose to move from the bloodstream into your cells, where it can be used for energy.

    Biguanides are taken twice a day. The only medication in this class is metformin (Glucophage). It’s often prescribed as a first-line treatment for type 2 diabetes. A potential side effect of metformin is diarrhea, but you can reduce this risk by taking it with food. 

    Thiazolidinediones are taken once a day with or without food. Pioglitazone (Actos) is an example of a thiazolidinedione. 

    Talk with your doctor about the potential side effects of thiazolidinediones. They may increase the risk of heart problems in some people.

    Alpha-glucosidase inhibitors slow the breakdown of starches, such as bread, pasta, and potatoes, into sugar. This helps slow the rise of blood sugar after you eat. Examples include:

    • acarbose (Precose) 
    • miglitol (Glyset)

    Alpha-glucosidase should be taken with the first bite of each meal, so many people take them three times a day. They may cause GI side effects, such as gas and diarrhea.

    SGLT2 inhibitors help lower blood sugar by preventing glucose from being reabsorbed in the kidney. Excess glucose instead leaves your body through urine. Examples of SGLT2 inhibitors include:

    • bexagliflozin (Brenzavvy)
    • canagliflozin (Invokana)
    • dapagliflozin (Farxiga)
    • empagliflozin (Jardiance)
    • ertugliflozin (Steglatro)

    SGLT2 inhibitors are taken once a day. In addition to lowering blood sugar, they may also help lower blood pressure and improve outcomes for people with heart or kidney disease. Potential side effects of SGLT2 inhibitors include yeast infections and urinary tract infections.

Frequently Asked Questions

As of 2023, beta cell regeneration and Immunotherapy are two potentially new treatments for diabetes that show promise. There are also recent advancements in insulin formulations and affordability through the production of biosimilars, or cheaper medications that are biologically similar to more expensive options on the market.

There are a number of ongoing clinical trials for type 2 diabetes research. The National Institutes of Health (NIH) offers a clinical trials database with details on current trials as well as how to enroll. The American Diabetes Association (ADA) also provides a list of type 2 diabetes trials on which they collaborate.

Ongoing T2D research continues to investigate immunotherapy and regenerative medicine. There are a number of clinical trials that consider pharmacologic, behavioral, surgical, and practice-level approaches to treating and preventing type 2 diabetes.

There are a number of new treatments for T2D that have recently become available to consumers. These include bexagliflozin (Brenzavvy, TheracosBio), which has been approved by the Food and Drug Administration (FDA) for the treatment of adults with type 2 diabetes, as well as Tirzepatide, a new GLP-1 receptor agonist approved in the United States as a supplement to diet and exercise.