All About Oral Diabetes Medication

Why, When, and How to Take Your Oral Medicines

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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 diabetes. And believe it or not, there actually is a method for prescribing these medicines. Both the American Diabetes Association (ADA) and the American Association of Clinical Endocrinologists (AACE) have specific algorithms that they suggest clinicians use when prescribing medication which should be personalized.

The American Diabetes Association guidelines state that medication prescription 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 risk, and patient preferences. There is an algorithm as to which medicines to start first, but again all of this is subjective based on the actual patient. And all medicines are prescribed as an adjunct to diet and exercise - lifestyle changes are always important. If you aren't aware of all the diabetes medicines out there, here is a brief synopsis of each one: 

The First Line of Defense: 

Metformin, a biguanide, remains the most widely used first-line type 2 diabetes drug. 

1. Class of Medication: Biguanides

Name of Medication (Generic & Brand Name)

  • Fortmate, Glucophage, Glucophage XR, Glumetza, Riomet (Metformin)

What it Does & How to Take it:

  • Usually used as the first medicine for diabetes.
  • Inhibits the liver from releasing too much glucose (sugar).
  • May also reduce insulin resistance (makes your body more sensitive to insulin in your body).
  • Take with food to prevent side effects such as upset stomach, nausea, or diarrhea, b12 deficiency and rare lactic acidosis. Increase dose as tolerated. 
  • Usually taken once to twice a day and is dosed 500-2550mg daily. 

Potential Side Effects:

  • Upset stomach, nausea, diarrhea, gas, headache

Cost: 

  • About $4 per month.

Other Important Information About This Medication:

  • Expected to reduce A1c 1-1.5%. 
  • May reduce some cancer risks.
  • Can be heart healthy. 
  • Can be used in certain people with prediabetes to help prevent Type 2 diabetes.
  • It has been around for a long time and is related to a substance found in a French lilac plant. 
  • Metformin should be started at a low dose and increased gradually to prevent side effects.
  • If you were prescribed standard metformin and are not tolerating it, ask your health care provider about the extended release version which may be easier on your stomach.
  • If you have a history of kidney, liver, or coronary heart failure you should discuss with your physician before starting this medication.
  • If you drink alcohol excessively, you should discuss with your health care provider before starting this medicine.  

2. Class of Medication: Thiazolidinediones (TZDs)

Actos, or pioglitazone is a class of medicines called Thiazolidinediones, and can be used as a first or second line agent for people with diabetes. Another agent of this class, rosiglitazone (Avandia), 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 it's limited use we will not discuss rosiglitazone. 

Name of Medication (Generic & Brand Name)

  • Pioglitazone (Actos)

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 6-8 weeks to start working and 6-8 weeks to leave your system. 
  • Dosing: 15, 30, 45mg daily

Potential Side Effects:

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

Other important Information You Should Know:

  • Expected to reduce A1c: 1.5%
  • 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 history of bladder cancer or a family history of bladder cancer you should discuss it with your healthcare provider before starting this medication. 

3. Class of 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 reduce mealtime blood sugars. They should be used with caution in the elderly because this population is at increased risk of developing low blood sugars.

Name of Medication (Generic & Brand Name)

  • Glimepiride (Amaryl) 
  • Glyburide  (Diabeta, Micronase)
  • Glipizide (Glucotrol, GlucotrolXL)

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 with increase insulin output. 
  • Take this medication before you eat, if you skip a meal do not take it.
  • Usual Dosing: 
    • Glipizide: 2.5-10mg once or twice a day 
    • Glipizide ER: 5-20mg once per day 
    • Glyburide: 2.5-10mg daily
    • Glimepiride: 1-4mg 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: Inexpensive medicine ~$4/month. 

Other Important Information about This Medication:

  • Expected to reduce A1c: 2%, but this diminishes over time. The longer you have had diabetes the more likely this medicine may not work for you if your sugars are not controlled. 
  • 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.

4. Class of Medication: Meglitinides

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

Name of Medication (Generic & Brand Name)

  • 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 15-30 minutes before the start of each meal. If you skip a meal do not take it.
  • Usual Dosing: 
    • Repaglinide: .5-4mg three times a day
    • Nateglinide: 60-120mg three times a day

Potential Side Effects:

  • Low blood sugar, upper respiratory infection, headache, diarrhea, weight gain.

Cost: Can be expensive.

Other Important Information About This Medication:

  • Expected to reduce A1c: 1%.
  • If you skip meals, frequently discuss with your primary health provider as this medication may not be the one for you.  

5. Class of Medication: DPP-4 Inhibitors

DPP-4 Inhibitors are typically used as a second line agent to help lower after meal sugars.

Name of Medication (Generic & Brand Name)

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

What it Does & How to Take it:

  • Increase 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: 
    • Januvia: 100mg daily unless you have kidney disease 
    • Onglyza: 5mg daily unless you have kidney disease
    • Tradjenta: 5mg daily 
    • Nesina: 25mg daily unless you have kidney disease 

Potential Side Effects:

  • Upper respiratory infection, sore throat, or a 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 About This Medication:

  • Expected to reduce A1c about .5-1%.
  • 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.

6. Class of Medication: SLGT-2 Inhibitors

Name of Medication Generic and Brand

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

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.
  • Using Dosing: 

Potential Side Effects:

  • Urinary tract infection or yeast infections, dehydration, bladder cancer. 

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 About This Medication:

  • Expected to reduce A1c about 0.5-0.7%. 
  • In contrast to other medications, they can be added on with similar efficacy as a 3rd or 4th agent.
  • Yields an approximate 2-3kg (4.4-6.6lb) weight loss over the course of a year.
  • Lipids: Increased HDL (healthy cholesterol), LDL (bad cholesterol) and decreased Triglyceride (strongest lipid effect with Canagliflozin)
  •  Discuss with your health care provider if you have a history of kidney disease before taking this medication. 

7. Class of Medication: Alpha-Glucosidase Inhibitors

Name of Medication (Generic & Brand Name)

  • Miglitol (Glyset)
  • Acarbose (Precose)

What it Does & How to Take it:

  • Inhibits the breakdown of starches, thereby reducing blood sugars. 
  • Take with the first bite of each meal – usually taken 3x per day.
  • Usual dosing: 
    • Acarbose: 25mg three times a day - can increase to 50 or 100 with meals as tolerated
    • Miglitol: 25mg three times a day - can increase to 50 or 100 with meals as tolerated

Potential Side Effects:

  • Gas, diarrhea, abdominal pain, rash

Cost: Relatively inexpensive. 

Other Important Information About This Medication:

  • If you have a history of inflammatory bowel disease, GI obstruction, or other malabsorption syndromes discuss with your primary care provider as this medicine is not for you. 
  • If you experience low blood sugar (anything less than 70mg/dL), you must treat it with glucose tablets or skim milk, as the breakdown of other sugar sources is too slow.
  • May help people to eat fewer carbohydrates

8. Class of Medications: Bile Acid Sequestrant

This is not a typical diabetes medicine, it is usually used to reduce LDL (bad)cholesterol, but it can also help to reduce A1c.

What it Does and How to Take it: 

  • It reduces glucose absorption. 
  • Usual dosing: 
    • 3.75 g (either taken as a powder mixture or 6 tablets) 

Potential Side Effects: 

  • Constipation, nausea, and indigestion. 

Cost: Can be expensive. 

Other Important Information About This Medicine: 

  • Expected to reduce A1c: ~.5%
  • Welchol is contraindicated in individuals with a history of bowel obstruction, those with serum triglyceride (TG) concentrations of >500 mg/dL, or with a history of hypertriglyceridemia-induced pancreatitis.
  • Welchol may decrease the absorption of fat-soluble vitamins A, D, E and K. Patients on vitamin supplements should take their vitamins at least 4 hours prior to Welchol. 

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 perhaps one the combination medicines are good for you. Ask your physician about the following: 

Combination Oral Medicines

Brand Name (Generic Name)

Actoplus Met (pioglitazone metformin)
Avandamet (rosiglitazone maleate-metformin hydrochloride)

Avandaryl (rosiglitazone glimepiride)

Duetact (pioglitazone glimepiride)

Glucovance (glyburide metformin hydrochloride)

Janumet (sitagliptin/metformin HCl)

Janumet XR 

Jentadueto (linagliptin/metformin HCl)

Juvisync (sitagliptin and Simvastatin)

Kazano (alogliptin/metformin)

Kombiglyze XR (saxagliptin/metformin)

Metaglip (glipizide/metformin)

Oseni (alogliptin/pioglitazone)

Invokamet (canagliflozin/metformin HCl)

Xigudo XR (dapagliflozin/metformin HCl)

Sources: 

Inzucchi, Silvio, et. al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach position statement of the American diabetes association (ADA) and the European association for the study of diabetes (EASD). Diabetes Care. November 15, 2014: http://care.diabetesjournals.org/content/35/6/1364.full?sid=046a6218-e23b-42b3-854e-c781313f7425#ref-48

American Diabetes Association. What Are My Options? November 16, 2014: http://www.diabetes.org/living-with-diabetes/treatment-and-care/medication/oral-medications/what-are-my-options.html

dLife. Combination Oral Medicines. November 15, 2014: http://www.dlife.com/diabetes/oral_medications/metformin-combination

Welchol (colesevelam HCI). Prescribing Information. Daiichi Sankyo, Inc., Parsippany, NJ, 01/2014.

Epocrates. November 16, 2014: https://online.epocrates.com/rxmain

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