If one is good, two may be better: Combination therapy for diabetes
If one is good, two may be better: Combination therapy for diabetes
Potent drug cocktail slashes blood sugar levels
Combination therapy, the standard in AIDS treatment, may soon become the watchword for glucose control in diabetes. A study published in the New England Journal of Medicine shows that metformin and troglitazone, which work equally well when used separately to control blood sugar levels, form a potent combination that lowers blood glucose by an additional 18% to 21% when used together.1
The two drugs, taken orally, act on separate parts of the body to lower blood sugar levels. Metformin (Glucophage, Bristol-Myers Squibb Co., Princeton, NJ) decreases production of excess blood glucose by the liver. Troglitazone (Rezulin, Warner-Lambert, Morris Plains, NJ), helps muscle respond to insulin and absorb blood glucose.
"In combination, they had a nice added effect of further lowering blood glucose levels, further than a single agent alone," says Gerald I. Shulman, MD, PhD, professor of medicine and cellular and molecular physiology at Yale University in New Haven, CT, and one of the study's authors.
Yale medical school researchers, in conjunction with researchers from the Howard Hughes Medical Institute at Yale, studied the effects of the medications on 29 patients with Type II diabetes. For three months, patients took one of the drugs, and then for another three months, they took both drugs. Patients were prescribed a diet designed to maintain their baseline body weight.
During both metformin and troglitazone individual therapy, fasting and postprandial plasma glucose concentrations decreased by 20% and 25%, respectively. But when the two drugs were combined, fasting and postprandial plasma glucose concentrations dipped an additional 18% and 21%, respectively.
A second study of 350 diabetics by researchers in Texas, Arkansas, and New York confirmed that troglitazone used with insulin doses helped lower blood sugar levels.2
"The combined therapy was logical and reversed two abnormalities that patients with diabetes experience," says Shulman.
With the effectiveness of combination therapy now demonstrated, research will focus on finding the most effective combinations and dosages. "Our study indicates that this combination is effective," says Silvio E. Inzucchi, MD, leader of the study and an assistant professor of internal medicine at Yale University. "It is not an FDA-approved combination, but it is already being used."
Inzucchi says there are many specific details which have yet to be sorted out. "Which combination is most effective for which patients? That is, how does a physician decide which drug to start with first, which drug to add second, and when [or if] to try three drugs at a time?"
For patients with questions about developments in diabetes treatment, including but not limited to combination therapy, Inzucchi says physicians should stress that the key to their own health is glycemic control. "However they get there is relatively immaterial," he says. "Use whatever combination [medicines, diet, lifestyle changes, or even insulin] that works and is safe."
"The future of treatment in our Type II diabetic patients will likely be combination therapy since no single agent will reverse all of the abnormalities seen in our diabetic patients," says Shulman. "Therefore, it is essential that we understand the mechanism by which these novel oral medications lower patients' blood glucose. We then will be able to combine them in a rational fashion for effective treatment."
For more information on combination therapy for Type II diabetes, contact:
· Silvio E. Inzucchi, MD, Assistant Professor, Internal Medicine, Yale University, New Haven, CT. Telephone;:(203) 785-5564.
· Gerald I. Shulman, MD, PhD, Professor of Medicine and of Cellular and Molecular Physiology, Yale University, New Haven, CT. Telephone: (203) 785-5447.
References
1. Inzucchi SE, et al. Efficacy and metabolic effects of metformin and troglitazone in type II diabetes mellitus. N Engl J Med 1998; 338:867-872.
2. Schwartz S, et al. Effect of troglitazone in insulin-treated patients with type II diabetes mellitus. N Engl J Med 1998; 338:861-866.
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