An Overview of Oral Diabetes Medication

It's important to know what medications you are taking if you have diabetes. You should know what they do, when to take them, and why you are taking them. Increasing your awareness can help you to better manage your condition and avoid complications.

While there are guidelines to direct which drugs should be used at what stage of treatment, there is no one-size-fits-all solution.

For its part, the American Diabetes Association (ADA) advises that the choice of medications should be individualized, taking into account a person's age, medical history, blood sugar readings, cost of treatment, possible side effects, and—just as importantly—personal preferences.

Here's a brief overview of all the oral medications currently available to treat type 2 diabetes.

Biguanides

Biguanides, specifically the drug metformin, are the most commonly used first-line drugs for the treatment of type 2 diabetes. They act on the liver, the organ which is responsible for glucose (sugar) to fuel cells.

Medication Names

• Brand names: Fortamet, Glucophage, Glucophage XR (extended-release), Glumetza, Riomet
• Generic name: metformin

What It Does

• Metformin prevents the liver from releasing too much glucose.
• Metformin helps reduce insulin resistance (in which your body is less sensitive to the effects of insulin).
• Metformin can reduce your A1C (the measurement of your average blood sugar over the past three months) by 1%.

How to Take It

• Take metformin with food to prevent side effects, such as upset stomach, nausea, or diarrhea.
• Metformin should be started at a low dose and increased gradually to achieve glycemic (glucose) control.
• Metformin is taken once to twice daily.
• Usual dosing: 500 to 2,000 milligrams (mg) daily

Potential Side Effects

• Upset stomach
• Nausea
• Diarrhea
• Gas
• Headache
• Weight loss
  

Other Important Information

• Metformin can be used in certain people with prediabetes to prevent type 2 diabetes.
  
• If you drink alcohol or have a history of kidney disease, liver disease, heart attack, or stroke, advise your healthcare provider before starting metformin.
• Metformin costs about $4 per month.

Thiazolidinediones

Thiazolidinediones can be used alone or in combination with other medications to help with insulin resistance and glycemic control, particularly when first-line medications cannot be used. There is one oral thiazolidinedione available for us.

Medication Names

• Actos (pioglitazone)

What It Does

• Actos works mainly on the muscle and fat cells to make the cells use insulin more efficiently. This means that glucose can enter the cells more easily to be used for energy.
• Actos can reduce A1C by about 1% to 1.25%.

How to Take It

• Actos is taken once daily with or without meals.
• Usual dosing: 15, 30, or 45 mg daily

Potential Side Effects

• Swelling in feet or hands due to fluid retention
• Weight gain
• Increased risk of fractures

Other Important Information

• It takes six to eight weeks for Actos to start working and the same amount of time for the drug to leave your system.
• Actos is not recommended for people with congestive heart failure.
• Because Actos can cause liver toxicity, it is important to get routine liver function tests.
• If you have a personal or family history of bladder cancer, advise your healthcare provider before starting Actos. 

Sulfonylureas

Sulfonylureas are a class of medications that have been around for a long time and are usually used as a secondary agent to help control mealtime blood sugars.

Medication Names

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

What It Does

• Sulfonylureas stimulate the pancreas to release more insulin, immediately following meals and for several hours after. Regardless of whether your blood sugar is high or low, these medications will increase insulin output.
• Sulfonylureas can reduce A1C by 1.25%,

How to Take It

Take this medication before you eat. If you skip a meal, do not take it.

Usual dosing:

• Amaryl: 1 to 4 mg daily
• Diabeta, Glynase: 2.5 to 10 mg daily
• Glucotrol: 2.5 to 10 mg once or twice a day 
• Glucotrol XL: 5 to 20 mg once per day 

The dose may need to be adjusted based on your activity level, weight, or calorie intake.

Potential Side Effects

• Sulfonylureas can cause hypoglycemia (low blood sugar). Always carry a fast-acting carbohydrate with you (such as glucose tablets, juice, or glucose gel) in case of a hypoglycemic attack.
• Weight gain

Other Important Information

• Sulfonylureas should be used with caution in older adults due to an increased risk of hypoglycemia.
• If you have poorly-controlled diabetes, sulfonylureas may not work well for you.
• Sulfonylureas cost about $4 per month.

Meglitinides

Meglitinides are similar to sulfonylureas in that they work to increase insulin output, but they are shorter acting. These medicines are often good for older people who need help with lowering their mealtime blood sugar.

Medication Names

• Prandin (repaglinide)
• Starlix (nateglinide)

What It Does

• Meglitinides work on the pancreas to produce more insulin to reduce after-meal blood sugar spikes.
• Meglitinides can reduce A1C by 0.75%.

How to Take It

Take this medication 15 to 30 minutes before the start of each meal. If you skip a meal, do not take it.

Usual dosing:

• Prandin: 0.5 to 4 mg three times a day
• Starlix: 60 to 120 mg three times a day

Potential Side Effects

• Low blood sugar
• Upper respiratory infection
• Headache
• Diarrhea
• Weight gain
  

Other Important Information

• If you skip meals frequently, mention this to your health provider. This medication may not be right for you.  
• Prandin and Starlix can be expensive, retailing from between $350 to $550 per month.

DPP-4 Inhibitors

Dipeptidyl peptidase-4 (DPP-4) inhibitors are typically used as a second-line agent to help lower after-meal blood sugar.

Medication Names

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

What It Does

• DPP4 inhibitors increase insulin production in your pancreas when your blood sugar is high, especially after you eat.
• DPP4 inhibitors also reduce the amount of sugar made by your liver, especially after you eat when your body doesn't need it.
• DPP4 inhibitors can reduce A1C by 0.75%.

How to Take It

Take this medication once a day at any time. It only works when it comes into contact with sugar, so it should not increase the risk of low blood sugar.

Usual dosing:

• Januvia: 100 mg daily
• Nesina: 25 mg daily
• Onglyza: 5 mg daily
• Tradjenta: 5 mg daily 
  

Potential Side Effects

• Upper respiratory infection
• Sore throat
• Headache
  

Other Important Information

• If you have a history of kidney disease or pancreatitis, advise your healthcare provider as these medications may not be right for you. For some people with kidney disease, the dose can be adjusted if the benefits of treatment outweigh the risks.
• If you are taking other medicines that decrease insulin output from the pancreas, you are at an increased risk of low blood sugar.
• DPP4 inhibitors can be expensive, ranging from $400 to $800 per month.

SGLT-2 Inhibitors

Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are typically a second-line or add-on medication that can help lower blood sugar by helping your kidneys remove excess sugar.

Medication Names

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

What It Does

• SGLT-2 inhibitors work with your kidneys to help remove excess glucose from your body when you urinate.
• SGLT-2 inhibitors can reduce A1C about 0.5% to 0.7%.

How to Take It

Take this medication before your first meal of the day.

Usual dosing:

• Canagliflozin: 100 to 300 mg (unless you have kidney disease)
• Dapagliflozin: 5 or 10 mg
• Empagliflozin: 10 to 25 mg
• Ertugliflozin: 5 to 15 mg

Potential Side Effects

• Urinary tract infection
• Yeast infections
• Dehydration
• Weight loss

Diabetic ketoacidosis (the potentially deadly build-up of blood acids called ketones) is also a potential side effect of the drug class.

Other Important Information

• Unlike some of the other diabetes medications, SGLT-2 inhibitors can be added on as a third or fourth agent.
• SGLT-2 inhibitor can increase "good" HDL cholesterol and lower "bad" LDL cholesterol, reducing your risk of heart disease.
• Tell your healthcare provider if you have a history of kidney disease before taking this medication. Your renal (kidney) function will need to be routinely monitored.
• SGLT-2 may help slow the progression of kidney disease by improving urinary excretion.

GLP-1 Receptor Agonists

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are lab-made versions of a natural hormone called GLP-1 that helps regulate the release of glucose from the liver. They are intended for use when metformin and other diabetes drugs fail to control type 2 diabetes. There is one oral GLP-1 RA approved for the treatment of diabetes in the United States.

Medication Names

• Rybelsus (semaglutide)

What It Does

• Rybelsus prevents the liver from making too much glucose.
• Rybelsus helps the pancreas produce more insulin when needed.
• Rybelsus reduce the A1C by 2.2%.

How to Take It

• Rybelsus should be taken at least 30 minutes before the first food, beverage, or other oral medications of the day with no more than 4 ounces of water.
• Usual dosing: 3 mg once daily for 30 days, increasing to 7 mg once daily

Potential Side Effects

• Nausea
• Diarrhea
• Vomiting
• Decreased appetite
• Indigestion
• Constipation

Other Important Information

• Rybelsus has been known to cause pancreatitis (inflammation of the pancreas), diabetic retinopathy (damage to the eye’s retina), hypoglycemia, and acute kidney failure (usually reversible) in some people.
• The risk of hypoglycemia is increased when Rybelsus is combined with sulfonylureas or insulin.
• People with multiple endocrine neoplasia syndrome type 2 (MEN 2) should not use Rybelsus. MEN 2 is an inherited disorder that causes the formation of tumors on endocrine (hormone-producing) organs.
• People who have ever had medullary thyroid carcinoma (a type of thyroid cancer) should also avoid Rybelsus.
• Rybelsus retails for around $850 per month
  

Alpha-Glucosidase Inhibitors

Alpha-glucosidase inhibitors (AGIs) are medications that are used to help keep blood glucose from rising too rapidly after meals.

Medication Names

• Glyset (miglitol)
• Precose (acarbose)

What It Does

• AGIs delay the breakdown of carbohydrates in the small intestine, reducing the level at which blood sugars and insulin rise after meals.

How to Take It

AGIs are usually taken three times per day. Take the drug with the first bite of each meal.

Usual dosing:

• Glyset: 25 mg three times a day, increasing to 50 or 100 mg as needed.
• Precose: 25 mg three times a day, increasing to 50 or 100 mg as needed.
  

Potential Side Effects

• Gas
• Diarrhea
• Abdominal pain
• Rash
  

Other Important Information

• Do not take Glyset or Precose if you have a history of inflammatory bowel disease, bowel obstruction, or other malabsorption syndromes.
• AGIs can increase satiation (the feeling of fullness) for longer, reducing yoru intake of carbohydrates.
  
• AGIs cost between $15 to $55 per month.

Bile Acid Sequestrants

Bile acid sequestrants are not typical diabetes medicines. These drugs are usually used to lower "bad" LDL cholesterol but can also help to reduce your A1C.

Medication Names

• Colestid (colestipol)
• Welchol (colesevelam)
• Questran, Prevalite (cholestyramine)

What It Does

• Bile acid sequestrants reduce glucose absorption.
• Bile acid sequestrants can reduce A1C by about 0.5%.

How to Take It

The medication is usually taken once or twice daily with a meal.

Usual dosing:

• Colestid: 5 grams (g) in a powder form or 2 g in tablets
  
• Questran, Prevalite: 4 g in powder form
• Welchol: 1.87 g in powder form or 3.75 g in tablets

Potential Side Effects 

• Constipation
• Nausea
• Indigestion

Other Important Information 

• Welchol is avoided in people with a history of bowel obstruction or hypertriglyceridemia-induced pancreatitis (pancreas inflammation due to high triglycerides)
• Bile acid sequestrants may decrease the absorption of vitamin A, D, E, and K. To avoid this, vitamin supplements should be at least four hours prior to a dose. 

Dopamine Agonists

Dopamine agonists are usually prescribed when other diabetes drugs have not been able to control blood sugar after a few months. There is currently only one option.

Medication Names

• Cycloset (bromocriptine mesylate)

What It Does

• Cycloset (bromocriptine mesylate) works by affecting the way that the brain processes a hormone called dopamine. This has the effect of increasing a person’s insulin sensitivity, meaning the body does not need as much insulin to transform glucose into energy. 
• Cycloset can reduce A1C by 0.3 to 0.5%.

How to Take It

• Take Cycloset within two hours of waking in the morning.
• Usual dose: 0.8 mg once daily, increasing to a maximum of 4.8 mg as needed.

Potential Side Effects

• Nausea
• Fatigue
• Weakness
• Lack of energy
• Dizziness
• Vomiting
• Headache
• Runny Nose
• Constipation
• Diarrhea

Other Important Information

• Cycloset causes hypotension in 50% of users, leading to dizziness, nausea, and even fainting.
• A one-month supply of Cycloset costs around $270 for 2.4 mg tablets.

Fixed-Dose Combination Drugs

To simplify dosing and increase drug adherence (the ability to take medications routinely as prescribed), there are fixed-dose combination (FDC) drugs that combine two or more diabetes drug agents. If you have problems keeping track of your medicines and are missing doses, an FDC drug may be a good option for you.

Combination oral medicines include:

• Actoplus Met (pioglitazone/metformin)
• Avandamet (rosiglitazone/metformin)
• Avandaryl (rosiglitazone/glimepiride)
• Duetact (pioglitazone/glimepiride)
• Glucovance (glyburide/metformin)
• Glyxambi (empagliflozin/linagliptin)
• Invokamet (canagliflozin/metformin)
• Janumet, Janumet XR (sitagliptin/metformin)
• Jentadueto (linagliptin/metformin)
• Kazano (alogliptin/metformin)
• Kombiglyze XR (saxagliptin/metformin)
• Oseni (alogliptin/pioglitazone)
• Prandimet (metformin/repaglinide)
• Segluromet (ertugliflozin/metformin)
• Steglujan (ertugliflozin, sitagliptin)
• Synjardy (metformin/empagliflozin)
• Qternmet XR (dapagliflozin/metformin/saxagliptin)
• Xigudo XR (dapagliflozin/metformin)

Summary

There are 26 individual oral agents from 10 classes of drugs that can be used for the treatment of diabetes. Some can be used alone, while others are used in combination and/or for later-stage treatment when your blood sugar is not being adequately controlled. The selection of drugs can vary based on numerous factors, including your personal preferences.

There are also no less than 19 fixed-dose combination (FDC) drugs available that combine two or more diabetes drug agents. These reduce the number of pills you have to take each day and can often improve adherence.

A Word From Verywell

Oral diabetes drugs are very effective in controlling blood sugar but only if you take them. While you may think that skipping doses is no big deal, some drugs like meglitinides are unlikely to work while others like Actos will not reach their full potency if you don't commit to complete adherence.

If you have problems taking your medications as prescribed, be honest with your healthcare provider and tell them why. They may be able to offer tips on ways to improve your adherence or adjust treatment if it is causing intolerable side effects.