Oral Diabetes Medications

What are oral diabetes medications?

Oral diabetes medications (taken by mouth) help manage blood sugar (glucose) levels in people who have diabetes but still produce some insulin — mainly people with Type 2 diabetes and prediabetes.

The most effective management of Type 2 diabetes involves:

• Lifestyle and diet modifications.
• Exercise.
• Medications.

Together, you and your healthcare provider will determine a treatment plan that works best for you. You may also work with a dietitian. You’ll need to see your provider regularly to adjust your treatment as needed.

Providers may prescribe more than one oral diabetes medication at a time to achieve the best blood glucose management. You can take some oral diabetes medications alongside insulin injections.

People with gestational diabetes may also need to take oral medication (metformin) if dietary changes and exercise don’t help enough to keep their blood sugar levels within range.

Are there oral medications for Type 1 diabetes?

People with Type 1 diabetes must take synthetic insulin to manage the condition and to live. This may involve using:

• Multiple daily injections (MDI) of insulin.
• An insulin pump.
• Inhalable insulin.

There’s no pill form of insulin.

How do oral diabetes medications work?

All oral diabetes medications share one goal: To help lower blood glucose levels (and your A1c) to a healthy range.

A significant contributor to the development of Type 2 diabetes (and gestational diabetes) is insulin resistance.

Insulin resistance, also known as impaired insulin sensitivity, happens when cells in your muscles, fat and liver don’t respond as they should to insulin. Insulin is a hormone your pancreas makes. It allows your body to turn the glucose (sugar) you consume from food into energy. This is an essential, life-sustaining process.

As a result of insulin resistance, your pancreas has to release more insulin to try to keep your blood sugar levels in a healthy range. If your pancreas can’t release enough insulin, your blood sugar levels rise, causing hyperglycemia (high blood sugar). Long-term hyperglycemia can cause several health issues.

Insulin resistance is a complex phenomenon. Oral diabetes medications work in different ways to lower blood sugar, including helping your pancreas produce more insulin. Beyond medication, exercise is a key part of naturally reducing insulin resistance.

What are the types of oral diabetes medications?

There are several different classes of diabetes medications that work in different ways to help manage blood sugar levels. They include:

• Alpha-glucosidase inhibitors.
• Biguanides.
• Bile acid sequestrants (BASs).
• Dopamine-2 agonists.
• DPP-4 inhibitors (gliptins).
• Meglitinides (glinides).
• SGLT2 inhibitors.
• Sulfonylureas.
• Thiazolidinediones (TZDs).

Alpha-glucosidase inhibitors

Alpha-glucosidase inhibitors help lower blood sugar levels by blocking the breakdown of starches and some forms of sugar in your intestines. Starch is a carbohydrate in foods like potatoes, bread and rice. Carbohydrates (starch and sugar) increase your blood glucose levels the most compared to other nutrients (protein and fat) you get from food.

Side effects of alpha-glucosidase inhibitors may include gas (flatulence), bloating and diarrhea.

Alpha-glucosidase inhibitors include:

• Acarbose (Precose®).
• Miglitol (Glyset®).

Biguanides

Biguanides lower blood glucose levels by decreasing the amount of glucose your liver produces and releases into your bloodstream. They also help lower blood glucose levels by making your muscle tissue more sensitive to insulin so it can absorb glucose for energy.

Side effects may include diarrhea, upset stomach and a metallic taste in your mouth.

Metformin is the main type of biguanide. Its brand names include:

• Glucophage®.
• Glucophage XR®.
• Glumetza®.
• Fortamet®.
• Riomet®.

Bile acid sequestrants (BASs)

Bile acid sequestrants are primarily cholesterol-lowering drugs. They can also help lower blood glucose levels, though researchers don’t know exactly how they do it. These drugs can be helpful since people with diabetes often have high cholesterol.

BASs help remove LDL cholesterol (low-density lipoproteins or the “bad” cholesterol). The drug prevents bile acid in your stomach from being absorbed into your blood. Your liver then needs the cholesterol from your blood to make more bile acid. This process lowers your cholesterol level.

Side effects may include gas and constipation.

The main BAS medication for Type 2 diabetes is colesevelam (Welchol®).

Dopamine-2 agonists

Dopamine-2 agonists reset your hypothalamic circadian rhythm, which obesity can affect. This reset helps reverse insulin resistance and causes a decrease in glucose production in your liver.

Bromocriptine (Cycloset®) is the only U.S. Food and Drug Administration (FDA)-approved dopamine-2 agonist to help treat Type 2 diabetes.

DPP-4 inhibitors (gliptins)

DPP-4 inhibitors (gliptins) help improve blood sugar levels by preventing the breakdown of GLP-1, a compound in your body.

GLP-1 naturally reduces blood glucose levels, but it normally breaks down and stops working very quickly. By interfering with this process, DPP-4 inhibitors allow GLP-1 to remain active in your body longer, lowering blood sugar levels only when they’re elevated. They can also increase satiety (feeling full after eating).

Possible side effects of DPP-4 inhibitors include headaches and gastrointestinal issues.

DPP-4 inhibitors include:

• Alogliptin (Nesina®).
• Linagliptin (Tradjenta®).
• Saxagliptin (Onglyza®).
• Sitagliptin (Januvia®).

Meglitinides (glinides)

Meglitinides are medications that stimulate your pancreas to release insulin. You take them before each meal to help prevent your blood sugar from increasing too much from the food. Because they increase insulin production, you’re more at risk for low blood sugar (hypoglycemia).

Meglitinides include:

• Nateglinide (Starlix®).
• Repaglinide (Prandin®).

SGLT2 inhibitors

SGLT2 inhibitors help lower blood glucose levels by sending extra glucose out of your body through your pee (urine). Glucose in your bloodstream passes through your kidneys. From there, the glucose can go into your pee or back into your body. SGLT2 inhibitors block your body’s ability to reabsorb glucose.

Side effects of SGLT2 inhibitors can include urinary tract infections (UTIs) and vaginal yeast infections. It can cause a serious complication called diabetes-related ketoacidosis (DKA), but this is rare.

SGLT2 inhibitors include:

• Canagliflozin (Invokana®).
• Dapagliflozin (Farxiga®).
• Empagliflozin (Jardiance®).

Sulfonylureas

Sulfonylureas stimulate your pancreas to release more insulin. Because they increase insulin production, you’re more at risk for low blood sugar (hypoglycemia).

All sulfonylurea drugs have similar effects on blood sugar levels, but they differ in side effects and interactions with other drugs. Sulfonylureas can interact with alcohol and cause vomiting, flushing or sickness. Ask your provider if you’re concerned about these side effects.

Sulfonylureas include:

• Glimepiride (Amaryl®).
• Glipizide (Glucotrol® and Glucotrol XL®).
• Glyburide (Micronase®, Glynase®, Glycron® and Diabeta®).

Thiazolidinediones (TZDs)

Thiazolidinediones help your muscle and fat tissues be more sensitive to insulin. They also reduce glucose production in your liver.

TZDs can cause water retention and increase the risk of heart failure in some people.

Thiazolidinediones include:

• Rosiglitazone (Avandia®).
• Pioglitazone (Actos®).

What is the most common oral medication for Type 2 diabetes?

Metformin is the most common oral medication for Type 2 diabetes. It’s been around a long time and is very well studied. Because of this, healthcare providers often recommend trying metformin first.

Providers also prescribe metformin as the first choice for gestational diabetes if medication is necessary.

What are the side effects of oral diabetes medications?

All medications have possible side effects, including oral diabetes medications. Each type of diabetes medication can cause different issues.

Ask your healthcare provider about the possible side effects of the diabetes medication you’re considering starting. Your pharmacist can also answer questions.

In general, common side effects of oral diabetes medications include gastrointestinal issues, such as:

• Diarrhea.
• Constipation.
• Bloating.
• Gas (flatulence).
• Upset stomach.
• Nausea.

Can I take oral diabetes medications if I’m pregnant or thinking of becoming pregnant?

Healthcare providers recommend stopping all Type 2 diabetes oral medications during pregnancy except for metformin. It’s the only oral diabetes medication that the U.S. FDA considers safe during pregnancy.

If you have Type 2 diabetes and become pregnant, your healthcare team may recommend using insulin to manage your blood sugar levels during the pregnancy.

Be sure to talk to your healthcare provider if you have Type 2 diabetes and are thinking of becoming pregnant.

Do oral diabetes medications interact with other drugs?

All diabetes pills can interact with other medications. Because of this, you must tell your healthcare provider about all the medications you’re taking, including prescriptions, supplements and over-the-counter medications.

While you're taking oral diabetes medications, you should check with your provider before starting anything new.

Sulfonylureas, thiazolidinediones and meglitinides are most likely to interact with other drugs.

Can I overdose on oral diabetes medications?

Always take your medications as prescribed by your healthcare provider. Read the directions carefully and follow them. If you’re unsure how much you’re supposed to take, call your provider.

One particular risk of taking certain oral diabetes medications is low blood sugar (hypoglycemia).

As oral diabetes medications work by lowering your blood sugar levels, if your dose is too high or you take more than what’s prescribed, you could experience hypoglycemia — blood sugar that’s lower than 70 mg/dL. This risk is especially increased with meglitinides and sulfonylureas.

Without proper treatment, severe hypoglycemia can be life-threatening. Hypoglycemia symptoms include:

• Shaking or trembling.
• Sweating and chills.
• Dizziness or lightheadedness.
• Weakness.
• Faster heart rate.
• Intense hunger (hyperphagia).
• Difficulty thinking and concentrating.
• Anxiousness or irritability.
• Pale skin (pallor).
• Nausea.

To treat hypoglycemia, you need to consume sugar or carbohydrates:

• Eat or drink 15 grams of carbs, such as half a banana or half a cup of apple juice, to raise your blood sugar.
• After 15 minutes, check your blood sugar.
• If it’s still below 70 mg/dL, have another 15 grams of carbs.
• Repeat until your blood sugar is at least 70 mg/dL.

If a person experiencing low blood sugar is unresponsive or unconscious, don’t give them food or liquid. They could choke. Call 911 and get medical help as soon as possible.

A note from Cleveland Clinic

There’s no “best” oral medication for Type 2 diabetes. Every person is unique and so is each treatment plan. You may need to try more than one type of pill, a combination of pills or insulin in addition to pills. It’s important to remember that diet modifications and exercise are essential parts of managing diabetes. Talk to your healthcare provider about any issues you’re having with your management. They’re available to help.