Diabetes Drugs That Improve Insulin Sensitivity

Medically Reviewed by Michael Dansinger, MD on May 24, 2022
3 min read

If you have type 2 diabetes, chances are you take medicine to help manage it, along with lifestyle steps such as following your doctor’s recommendations on nutrition and physical activity. Many diabetes drugs lower blood sugar in different ways. Some help your body make better use of insulin, the hormone that helps your body manage your blood sugar.

Two types, or classes, of diabetes drugs make your cells more open or sensitive to insulin. These medications are biguanides and thiazolidinediones (TZDs).

The only drug in this class is called metformin (Glucophage, Glucophage XR, Riomet). It’s usually the first drug that doctors recommend. Metformin lowers blood sugar (glucose) because it helps insulin work better. This means more sugar leaves your blood and enters your cells. Metformin also lowers the amount of glucose your liver makes so there’s less in your bloodstream.

Unlike with some diabetes pills, weight gain isn’t a typical side effect. You might even shed a few pounds. Metformin may also help prevent heart attacks. Plus, it won’t break the bank. Sixty 500-milligram (mg) tabs cost about $4.


Metformin comes in three forms: immediate-release pills, extended-release pills, and a liquid. You take immediate-release pills and liquid twice a day, with breakfast and dinner. You take extended-release pills once a day. Your dose depends on how well you do on them. You’ll likely start with a low dose and work up slowly.

You shouldn’t take metformin if you have advanced kidney disease, type 1 diabetes, or are an older adult with prediabetes. As with any new treatment, talk about the benefits and risks with your doctor before you start taking it.

Side effects

Metformin can cause diarrhea, nausea, vomiting, and belly pain. These symptoms usually get better, as your body adjusts to the medicine, but can last longer. It’s important to take your meds with your first bite of food. Switching to extended-release tabs may help, too.

It’s rare, but metformin can also cause a life-threatening problem called lactic acidosis. Symptoms include cramps, nausea, weakness, and fast breathing. If you think you have lactic acidosis, get emergency care right away.

There are two drugs in this class: pioglitazone (Actos) and rosiglitazone (Avandia). They help your cells use insulin better and lower the amount of glucose your liver makes. If you have a history of congestive heart failure, you shouldn’t take this kind of medication because it could worsen that condition. Doctors usually consider prescribing metformin before considering TZDs.


With pioglitazone, your doctor will probably first prescribe a low daily dose: around 15 mg. Your doctor may raise the dose slowly to 30 or 45 mg a day. You’ll take tests to see how well your liver is working before and during treatment.

If your doctor prescribes rosiglitazone, your prescription may be for 4-mg or 8-mg tablets once a day or divided and taken twice a day.

Side effects

Apart from swelling and weight gain, TZDs can have serious side effects, including a greater chance of heart failure and fractures. Talk these risks over with your doctor.