An Overview of Oral Diabetes Medication

It's important to know what medications you are taking for 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 improve your overall wellness.

Close up of man holding a glass of water and medication in his hand
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The American Diabetes Association (ADA) guidelines state that medication choices should be based on a patient-centered approach, taking into consideration blood sugars, past medical history, age, efficacy, cost, potential side effects, effects on weight, hypoglycemia (low blood sugar) risk, and patient preferences.

There is an algorithm to decide which medicines to start first, but all of this is subjective based on the actual patient. Importantly, all medicines are prescribed as an adjunct to diet and exercise—lifestyle changes are incredibly important in diabetes treatment.

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

Biguanides

Metformin, a biguanide, has long been the standard of care in first-line type 2 diabetes treatment.

Updated clinical guidelines from the ADA note that patients with certain risk factors, including cardiovascular or kidney conditions, can benefit from starting metformin plus another class of medications in combination.

Medication Names:

  • Fortmate, Glucophage, Glucophage XR (extended release), Glumetza, Riomet
  • Generic for all: metformin

What It Does & How to Take It:

  • Inhibits the liver from releasing too much glucose (sugar).
  • May also reduce insulin resistance (i.e., makes your body more sensitive to insulin).
  • Take with food to prevent side effects, such as upset stomach, nausea, or diarrhea, b12 deficiency, and rare lactic acidosis.
  • Should be started at a low dose and increased gradually to prevent side effects.
  • Taken once to twice a day

Usual dosing:

  • 500 to 2000 milligrams (mg) daily

Potential Side Effects:

  • Upset stomach
  • Nausea
  • Diarrhea
  • Gas
  • Headache

Cost: 

  • About $4 per month

Other Important Information:

  • Can reduce A1C by 1%.
  • Can be heart-healthy. 
  • May reduce some cancer risks.
  • Can be used in certain people with prediabetes to help prevent type 2 diabetes. 
  • If you were prescribed standard metformin and are not tolerating it, ask your healthcare provider about the extended-release version which may be easier on your stomach.
  • If you have a history of kidney disease, liver disease, heart attack, or stroke, you should discuss with your physician before starting this medication.
  • If you drink alcohol excessively, you should discuss this with your healthcare provider before starting this medicine.  
  • May also cause weight gain.

January 6, 2021: The Food and Drug Administration (FDA) has requested that a manufacturer of an additional formulation of extended-release metformin voluntarily withdraw the product from the market. This adds to the list of recalled metformin products that the agency identified as having unacceptable levels of N-Nitrosodimethylamine (NDMA).

Patients should continue taking their metformin as prescribed until their health professional is able to prescribe an alternative treatment, if applicable. Stopping metformin without a replacement can pose serious health risks to patients with type 2 diabetes.

Thiazolidinediones

Actos (pioglitazone) is in a class of medicines called thiazolidinediones (TZDs) and can be used as a first- or second-line agent for people with diabetes. 

Another agent of this class, Avandia (rosiglitazone), is no longer widely available, owing to concerns of increased heart attack risk—but, it is no longer restricted. For the purpose of this article, and its limited use, information about rosiglitazone will not be included. 

Medication Names:

  • Actos (pioglitazone)

What It Does & How to Take It: 

  • 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.
  • Take once daily—can be taken without regard to meals.
  • Takes about six to eight weeks to start working and the same amount of time to leave your system. 

Usual dosing:

  • 15, 30, or 45 mg daily

Potential Side Effects:

  • May cause swelling in feet or hands from fluid retention
  • Weight gain
  • Increases risk of fractures

Other Important Information:

  • Can reduce A1C by about 1% to 1.25%.
  • This medication is not recommended in patients with congestive heart failure.
  • It’s important to get routine liver function tests.
  • Contact your health provider immediately if you have excessive weight gain or swelling in the legs, feet, or hands.
  • If you have a personal or family history of bladder cancer, you should discuss it with your healthcare provider before starting this medication. 

Sulfonylureas

Sulfonylureas are a class of medications that have been around for a long time and are usually used as a second agent to help control mealtime blood sugars. They should be used with caution in the elderly because this population is at increased risk of developing low blood sugars.

Medication Names:

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

What It Does & How to Take It:

  • Works on the pancreas to release more insulin, both right after a meal and then over several hours. Regardless of whether your blood sugar is high or low, this medication will increase insulin output.
  • Take this medication before you eat. If you skip a meal, do not take it.

Usual dosing:

  • Glipizide: 2.5 to 10 mg once or twice a day 
  • Glipizide extended release: 5 to 20 mg once per day 
  • Glyburide: 2.5 to 10 mg daily
  • Glimepiride: 1 to 4 mg daily 

Potential Side Effects:

  • These medicines can cause low blood sugar, therefore you should always carry a source of fast-acting carbohydrate with you, such as glucose tablets, juice or glucose gel.
  • Weight gain

Cost:

  • About $4 per month.

Other Important Information:

  • Can reduce A1C by 1.25%.
  • If you have had diabetes with poorly-controlled blood sugar for an extended period of time, this medication may not work well for you.
  • Follow your meal plan and activity program. Call your healthcare provider if your blood glucose levels are consistently low. If there is an increase in your activity level or reduction in your weight or calorie intake, the dose may need to be lowered.

Meglitinides

Meglitinides are similar to sulfonylureas in that they work to increase insulin output, but they are shorter acting. These medicines are typically good for older patients who need help with lowering their mealtime sugars. However, they must be taken three times a day. 

Medication Names:

  • Prandin (repaglinide)
  • Starlix (nateglinide)

What It Does & How to Take It:

  • Works on the pancreas to produce more insulin to reduce after-meal blood sugars.
  • Take 15 to 30 minutes before the start of each meal. If you skip a meal, do not take it.

Usual dosing:

  • Repaglinide: 0.5 to 4 mg three times a day
  • Nateglinide: 60 to 120 mg three times a day

Potential Side Effects:

Cost:

  • Can be expensive.

Other Important Information:

  • Can reduce A1C by .75%.
  • If you skip meals, frequently discuss with your primary health provider as this medication may not be the one for you.  

DPP-4 Inhibitors

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

Medication Names:

What It Does & How to Take It:

  • Increases insulin production in your pancreas when your blood sugar is high, especially after you eat.
  • Reduces the amount of sugar made by your liver, especially after you eat, when your body doesn't need it.
  • Take this medication once a day at any time. It only works when it comes into contact with sugar, therefore it should not increase the risk of low blood sugar.

Usual dosing:

  • Sitagliptin: 100 mg daily unless you have kidney disease 
  • Saxagliptin: 5 mg daily unless you have kidney disease
  • Linagliptin: 5 mg daily 
  • Alogliptin: 25 mg daily unless you have kidney disease 

Potential Side Effects:

  • Upper respiratory infection
  • Sore throat
  • Headache

Cost:

  • Expensive: Contact your insurance provider to see which medicine is the preferred agent on your plan before filling a prescription. 

Other Important Information:

  • Can reduce A1C by .75%
  • Januvia, Onglyza, and Nesina are excreted through the kidneys. People who have decreased kidney function may need to have their dose adjusted.
  • If you have a history of kidney disease or pancreatitis, you should notify your physician as these medications may not be right for you.
  • If you are taking other medicines that tell your pancreas to make insulin, you are at an increased risk of having a low blood sugar.

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 causing your kidneys to remove excess sugar.

Medication Names:

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

What It Does & How to Take It:

  • Works with your kidneys to help remove excess glucose (sugar) from your body when you urinate.
  • Take before your first meal of the day.

Usual dosing:

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

Potential Side Effects:

Cost: 

  • Can be expensive: Contact your insurance provider to see which medicine is the preferred agent on your plan before filling a prescription. 

Other Important Information:

  • Can reduce A1C about 0.5% to 0.7%
  • In contrast to other medications, they can be added on with similar efficacy as a third or forth agent.
  • Yields an approximate 2 to 3 kilogram (kg), or 4.4 to 6.6 pound (lb), weight loss over the course of a year.
  • Lipids: Increases HDL (healthy cholesterol) and LDL (bad cholesterol); canagliflozin and dapaglifozin may also decrease triglycerides
  • Discuss with your healthcare provider if you have a history of kidney disease before taking this medication. 
  • Canagliflozin, dapaglifozin, and empaglifozin have shown a cardiovascular protection benefit and may reduce or slow the progression of kidney disease.

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 & How to Take It:

  • Delays the breakdown of carbohydrates in the small intestine, thereby reducing the rise in blood sugars and insulin levels after meals.
  • Take with the first bite of each meal. Usually taken three times per day.

Usual dosing:

  • Acarbose: 25 mg three times a day; can increase to 50 or 100 mg with meals as tolerated
  • Miglitol: 25 mg three times a day; can increase to 50 or 100 mg with meals as tolerated

Potential Side Effects:

  • Gas
  • Diarrhea
  • Abdominal pain
  • Rash

Cost: 

  • Relatively inexpensive

Other Important Information:

Bile Acid Sequestrants

Bile acid sequestrants are not typical diabetes medicines. While these drugs are usually used to reduce LDL (bad) cholesterol, they can also help to reduce A1C.

Medication Names:

What It Does and How to Take It: 

  • It reduces glucose absorption.

Usual dosing:

  • Colesevelam: 1.87 grams (g) or 3.75 g in a powder mixture or in tablets
  • Colestipol: 5 g in a powder mixture or 2 g in tablets
  • Cholestyramine: 4 g in powder mixture

Potential Side Effects: 

  • Constipation
  • Nausea
  • Indigestion

Cost: 

  • Can be expensive

Other Important Information: 

  • Can reduce A1C by about 0.5%
  • Welchol is contraindicated in individuals with a history of bowel obstruction, those with serum triglyceride (TG) concentrations of >500 mg/dL, or those with a history of hypertriglyceridemia-induced pancreatitis.
  • Bile acid sequestrants may decrease the absorption of fat-soluble vitamins A, D, E and K. Patients on vitamin supplements should take their vitamins at least four hours prior to the medication. 

Combination Medicines

To simplify things and increase compliance, many medicines have been combined together. If you are taking metformin and another agent but typically forget to take all your medicines, a combination medicine 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)
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Article Sources
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