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.

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.

Medication Names

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

What It Does

• Inhibits the liver from releasing too much glucose (sugar)
• May also reduce insulin resistance (i.e., makes your body more sensitive to insulin)
• Can reduce A1C by 1%

How to Take It

• Take with food to prevent side effects, such as upset stomach, nausea, or diarrhea
• 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 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 cause weight loss

Thiazolidinediones

Thiazolidinediones (TZDs) can be used as a first- or second-line agent for people with diabetes. 

Medication Names

• Actos (pioglitazone)

Note: 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. 

What It Does

• 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.
• Can reduce A1C by about 1% to 1.25%

How to Take It

• Once daily without regard to meals
• Usual dosing: 15, 30, or 45 mg daily

It takes about six to eight weeks to start working and the same amount of time to leave your system. 

Potential Side Effects

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

Other Important Information

• 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.

Medication Names

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

What It Does

• 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.
• 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:

• 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

If there is an increase in your activity level or reduction in your weight or calorie intake, the dose may need to be lowered.

Potential Side Effects

• These medicines can cause low blood sugar. 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

• These drugs should be used with caution in the elderly because this population is at increased risk of developing low blood sugars.
• 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.

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

• Works on the pancreas to produce more insulin to reduce after-meal blood sugars.
• Can reduce A1C by .75%.

How to Take It

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

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

Cost

• Can be expensive

Other Important Information

• If you skip meals frequently, mention that to your health provider. 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

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

What It Does

• 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.
• Can reduce A1C by .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:

• Sitagliptin: 100 mg daily*
• Saxagliptin: 5 mg daily*
• Linagliptin: 5 mg daily 
• Alogliptin: 25 mg daily*

^{*These drugs are excreted through the kidneys. People who have decreased kidney function may need to have their dose adjusted.}

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

• 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

• Works with your kidneys to help remove excess glucose (sugar) from your body when you urinate.
• Can reduce A1C about 0.5% to 0.7%

How to Take It

Take 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
• Increased risk of amputations (with Canagliflozin)

Euglycemic diabetic ketoacidosis (with glucose <250 mg/dL) is also a potential side effect of the drug class.

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:

• 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
• Tell 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

• Delays the breakdown of carbohydrates in the small intestine, thereby reducing the rise in blood sugars and insulin levels after meals.

How to Take It

Usually taken three times per day; take with the first bite of each meal.

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

• A history of inflammatory bowel disease, GI obstruction, or other malabsorption syndromes is a contraindication for these drugs.
• If you experience low blood sugar (anything less than 70 mg/dL), you must treat it with glucose tablets or gels, skim milk, or juice as the breakdown of other sugar sources is too slow.
• May help people to eat fewer carbohydrates. 

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

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

What It Does

• Reduces glucose absorption
• Can reduce A1C by about 0.5%

How to Take It

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 

• 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)