Combination Therapy - Treatment For Type 2 Diabetes: Diabetes A Plan For Living

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Combination therapy

Because all the oral medications for diabetes have limited potency, scientists have tried to take advantage of their different mechanisms by using them in various combinations, with or without insulin.

Traditionally, clinicians took a one-treatment-at-a-time approach to type 2 diabetes. If diet and exercise failed, the doctor put the patient on a sulfonylurea. Once the maximum dose was reached, a new medication was started, and once medication options were exhausted, insulin treatment began. But this approach was only modestly successful, with most type 2 diabetic patients unable to achieve near-normal blood sugar levels.

A multiple-drug approach fits the new view of diabetes as a complex disease with at least two deficits that can be addressed: insulin resistance and inadequate insulin secretion. The combination approach may use lower doses of drugs, each with different mechanisms. The most common and widely studied oral drug combination is metformin plus a sulfonylurea.

Some diabetes experts are now going a step further, arguing that people should be prescribed medications, and even insulin, in conjunction with a diet and exercise plan as soon as they're diagnosed. The rationale is that insulin-secreting beta cells may be most salvageable early in the course of the disease, so aggressive therapy may prevent blood sugar levels from worsening. While early combination drug therapy would be expensive, it might be cheaper in the long run than dealing with the complications of the disease. Combination pills currently available combine a sulfonylurea with either metformin or a TZD.

Combination therapy probably increases the risk for hypoglycemia. When you combine drugs that don't usually cause hypoglycemia with drugs that do, the combination leans toward causing low blood sugar.

TABLE 5 Oral medications for type 2 diabetes
Sulfonylureas
Generic name	Brand name	Use	Side effects	Comments
acetohexamide	Dymelor	1–2 doses a day; before breakfast and dinner	Increased risk for hypoglycemia; rarely may cause rashes, chest pain	Effectiveness declines over years. Should not be taken if allergic to sulfa drugs. May increase risk for cardiovascular disease. May lead to weight gain. May interact with other medications, which would require dose adjustments.
chlorpropamide	Diabinese	Once a day	Increased risk for hypoglycemia; rarely may cause rashes; possible water retention; may cause flushing and nausea with alcohol
glimepiride	Amaryl	Once a day, with breakfast Hypoglycemia; rash	Hypoglycemia; rash
glipizide	Glucotrol, Glucotrol XL	1–2 doses a day, before breakfast and/or dinner	Hypoglycemia; rash
glyburide	Glynase PresTab, DiaBeta, Micronase	1–2 doses a day, before breakfast and/or dinner	Hypoglycemia; rash
tolazamide	Tolinase	1–2 doses a day, before breakfast and/or dinner	Hypoglycemia; rash
tolbutamide	Orinase	2 doses a day, before breakfast and dinner	Hypoglycemia; rash; may cause changes in taste
Biguanides
Generic name	Brand name	Use	Side effects	Comments
metformin	Glucophage	2–3 times a day, with meals	Nausea, diarrhea, flatulence; rarely may cause lactic acidosis	Doesn't cause weight gain or hypoglycemia
Glucophage XR (extended release)	1–2 times a day
Alpha-glucosidase inhibitors
Generic name	Brand name	Use	Side effects	Comments
acarbose	Precose	3 times a day, with meals	Abdominal pain, diarrhea, flatulence	Moderate blood sugar surges after a meal. Not to be taken by people with inflammatory bowel disease or other intestinal diseases.
miglitol	Glyset	2–3 times a day, with meals
Thiazolidinediones
Generic name	Brand name	Use	Side effects	Comments
pioglitazone	Actos	1–2 doses a day	Anemia, edema, weight gain; may make birth control pills less effective	Liver enzymes should be checked at start of treatment and regularly thereafter. If you develop jaundice, stop taking the drug and contact a doctor immediately.
rosiglitazone	Avandia	1–2 doses a day
Meglitinides
Generic name	Brand name	Use	Side effects	Comments
nateglinide	Starlix	Taken with meals	Hypoglycemia, but less commonly than with sulfonylureas; also nasal congestion and weight gain	Work faster and have a shorter duration than sulfonylureas, which lowers the risk for hypoglycemia. May be safer than the sulfonylureas in older patients and in those with kidney failure.
repaglinide	Prandin	Taken with meals
Combination medications
Generic name	Brand name	Use	Side effects	Comments
glipizide and metformin	Metaglip	Taken with meals	May cause hypoglycemia, diarrhea, nausea; rarely may cause lactic acidosis	Combinations may be more convenient for people who have previously taken the two medications separately. The adverse events, precautions, and safety issues that apply to the individual components in each combination medication must also be considered for the combination.
glyburide and metformin	Glucovance	Taken with meals	May cause hypoglycemia, diarrhea, nausea, dark urine; rarely may cause lactic acidosis, rashes, and increased sensitivity to sunlight
rosiglitazone and metformin	Avandamet	Taken with meals	May cause hypoglycemia, diarrhea, nausea or edema; rarely may cause lactic acidosis

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Last updated:	January 23, 2007

Medical content reviewed by the Faculty of the Harvard Medical School. Harvard Health Publications, Copyright © 2007 by President and Fellows of Harvard College. All rights reserved. Used with permission of StayWell.

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