Type 2 diabetes - oral medicines

Type 2 diabetes may be controlled with meal planning, weight loss, and exercise. If these steps alone are not enough, you also may need oral medicines to help keep blood sugar in your target range.

Different oral diabetes medicines work in different ways to help control diabetes:

• Help the body produce insulin
• Increase the sensitivity of body tissues to insulin
• Help with carbohydrate digestion and absorption in the body

There are eight major classes of oral medicines for diabetes:

• Biguanides
• SGLT2 inhibitors
• Sulfonylureas
• DPP-4 Inhibitors
• Thiazolidinediones
• Alpha-glucosidase inhibitors
• Meglitinides
• Bile acid sequestrants

These medicines may be used alone or in combination.

BIGUANIDES

Metformin (Glucophage, Glumetza, Riomet, and Fortamet) is a biguanide. This is often the first oral medicine health care providers prescribe for type 2 diabetes.

Metformin is a medicine that stops the liver from making glucose. It also makes body tissues more sensitive to insulin.

This medicine:

• May help improve cholesterol levels
• May help people with diabetes lose some weight
• Has a low risk of low blood sugar

There are two types of metformin:

• Immediate-release: Taken 2 to 3 times a day
• Sustained-release: Taken as a single dose every day, most often with an evening meal

The most common side effect of metformin is diarrhea. Sometimes people taking metformin will become deficient in vitamin B12. If you have liver or kidney disease, tell your provider. People with liver or kidney disease or who are heavy drinkers should not take metformin.

SGLT2 INHIBITORS

SGLT2 inhibitors increase the amount of glucose that goes out in the urine. They may also lead to some weight loss and lower blood pressure in people with diabetes.

SGLT2 inhibitors include:

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

If you have kidney disease, tell your provider before taking these medicines. Side effects include urinary tract infections and yeast infections due to the presence of more sugar in the urine.

SULFONYLUREAS

These medicines help the pancreas produce insulin and help the body use glucose (blood sugar) for energy. Sulfonylureas include:

• Glipizide (Glucotrol)
• Glyburide (Diabeta, Glynase)
• Glimepiride (Amaryl)

Glipizide is taken 30 minutes before a meal. Glyburide and glimepiride are taken with meals.

In the beginning, your provider will:

• Start you on a low dose, taken once a day.
• Increase the dose every 1 to 2 weeks until your blood sugar level comes in range.

When you take sulfonylureas:

• Do not skip meals.
• Limit alcohol (ask your provider how much is safe for you).
• Always carry candy, juice, or sugar in case your blood sugar gets too low.

The most common side effect of sulfonylureas is hypoglycemia. Other side effects include weight gain, irritability, stomach upset, and skin rashes.

Tell your provider if your weight changes or if your blood sugar level is regularly low. Your provider will adjust the dosage of the medicine.

DPP-4 INHIBITORS

These medicines help the body release more insulin. They also lower the amount of glucose made by your body. DPP-4 inhibitors help lower blood sugar without causing hypoglycemia.

DPP-4 inhibitors include:

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

These medicines are taken once a day. Common side effects are:

• Muscle pain
• Stuffy nose
• Sore throat
• Respiratory infection
• Headache
• Stomach ache

These medicines can also cause severe joint pain. If you notice joint pain, contact your provider right away.

THIAZOLIDINEDIONES (GLITAZONES)

Pioglitazone (Actos) and rosiglitazone (Avandia) are in this group of medicines. They lower insulin resistance by making body tissues more sensitive to insulin. These medicines are taken 1 to 2 times a day with or without meals.

Side effects include:

• Weight gain
• Water retention (edema)
• Decreased bone density
• Increased risk of heart failure
• Increased risk for bladder cancer

If you have heart disease or liver disease, and are prescribed a thiazolidinedione medicine, ask your provider if it is safe to take it. If you have side effects, stop taking the medicine right away and tell your provider.

ALPHA-GLUCOSIDASE INHIBITORS

These medicines delay the digestion of carbohydrates (starches and sugars) in the body. This helps lower blood sugar after a meal. Acarbose (Precose) and miglitol (Glyset) are alpha-glucosidase inhibitors.

These medicines are taken with the first bite of each meal. Side effects include bloating, flatulence, and diarrhea.

MEGLITINIDES

Meglitinides such as repaglinide (Prandin) and nateglinide (Starlix) increase insulin production in the pancreas. Avoid alcohol when you are on these medicines.

These medicines:

• Are useful if you don't eat meals at regular times
• Can be taken anytime between 30 minutes before a meal up to mealtime

Side effects can include low blood sugar and stomach upset.

BILE ACID SEQUESTRANTS

These medicines lower blood sugar and cholesterol in people with diabetes. Bile acid sequestrants were originally used to treat high LDL (bad) cholesterol. These medicines also help lower blood sugar.

These medicines are often prescribed for people with type 2 diabetes who also have high cholesterol. They also may be used for people who have liver problems and can't take other medicines.

Cholestyramine (Prevalite, Questran) and colesevelam (Welchol) are bile acid sequestrants. Side effects include flatulence and constipation.

Oral diabetes medicines are often used in combination. Combining one medicine with another may give better blood sugar control than a single medicine.

It is likely that your provider will first recommend that you take metformin. If your blood sugar does not come within range in 3 months, metformin may be combined with another medicine. If your blood sugar target is still not in range after another 3 months, your provider may recommend a three-medicine combination.

Before prescribing oral medicines, your provider will consider the following:

• Risk of low blood sugar (hypoglycemia)
• Your history of heart, liver, or kidney disease
• Other medical conditions you may have such as high cholesterol
• The effect on your weight
• Side effects
• Cost

You and your provider can discuss your options and what will work best for you.

Low blood sugar (hypoglycemia) is common in people with diabetes who use medicines to control their diabetes. Severe low blood sugar is a medical emergency. It can cause seizures and brain damage. Be sure to ask your provider what you should do if you have symptoms of low blood sugar.

Also, be sure you know how to tell when your blood sugar is getting too low.

When your blood sugar does get too low, follow your provider's instructions on how to treat yourself. In general, you should eat or drink something with 15 grams of carbohydrates, such as:

• 3 glucose tablets
• 1/2 cup (118 mL) of fruit juice or non-diet soda
• 5 to 6 chewable candies such as jelly beans

Do not stop taking diabetes medicines suddenly or change the dosage without talking with your provider. Be sure to keep your provider appointments to make sure the medicines are working well.

Contact your provider if you have any of these symptoms or side effects:

• Low blood sugar
• Nausea and flatulence
• Diarrhea
• Skin rash
• Weight gain
• Stomach upset
• Headache
• Constipation

Oral medicines for type 2 diabetes; Type 2 diabetes - oral medicines; High blood sugar - oral medicines; Type 2 diabetes and oral medicines; Oral anti-diabetes medicines

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American Diabetes Association Professional Practice Committee. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2025. Diabetes Care. 2025 Jan 1;48(Supplement_1):S181-S206. PMID: 39651989 pubmed.ncbi.nlm.nih.gov/39651989/.

Dhatariya KK, Umpierrez GE, Crandall JP. Diabetes mellitus. In: Goldman L, Cooney KA, eds. Goldman-Cecil Medicine. 27th ed. Philadelphia, PA: Elsevier; 2024;chap 210.

Updated by: Sandeep K. Dhaliwal, MD, board-certified in Diabetes, Endocrinology, and Metabolism, Springfield, VA. Also reviewed by David C. Dugdale, MD, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team.