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Single-pill combinations: New therapy for Type 2 diabetes

Patients with Type 2 diabetes now have therapeutic options that combine two medications in one pill. The Food & Drug Administration recently approved Metaglip (glipizide/metformin, Bristol-Myers Squibb) and Avandamet (rosiglitazone/metformin, GlaxoSmithKline).

As stated in Metaglip's package insert (PI), the drug is indicated as initial therapy, in addition to diet and exercise, to improve glycemic control in patients with Type 2 diabetes whose hyperglycemia cannot be satisfactorily controlled with diet and exercise alone. It is indicated as second-line therapy in patients with Type 2 diabetes whose hyperglycemia cannot be adequately controlled with diet, exercise, and initial treatment with a sulfonylurea or metformin.

In the case of Avandamet, it is indicated as an adjunct to diet and exercise to improve glycemic control in patients with Type 2 diabetes who are already receiving treatment with a combination of rosiglitazone and metformin or who have inadequate glycemic control on metformin alone.

Metaglip and Avandamet became available in pharmacies last month.

Metaglip is available in several dosage strengths: 2.5 mg/250 mg, 2.5 mg/500 mg, and 5 mg/500 mg tablets. Avandamet comes in 1 mg/ 500 mg, 2 mg/500 mg, and 4 mg/ 500 mg tablets.

According to Barry Goldstein, M.D., Ph.D., director, division of endocrinology, diabetes, and metabolic diseases, Jefferson Medical College, Philadelphia, the contraindications for and adverse effects associated with Metaglip and Avandamet use are the same as those of the individual component drugs. Metaglip and Avandmet are contraindicated in patients with renal insufficiency, congestive heart failure requiring pharmacologic treatment, or acute or chronic metabolic acidosis. Both PIs have a boxed warning about the risk of lactic acidosis, due to metformin accumulation. Persons with hepatic insufficiency should avoid therapy with Metaglip or Avandamet. Adverse effects associated with Metaglip in clinical trials were diarrhea, nausea, and vomiting. Adverse effects associated with Avandamet were diarrhea and anemia.

The advantage of using combination therapy to treat Type 2 diabetes, said Goldstein, is that patients may reap additional clinical benefits from taking drugs with different, but complementary, mechanisms of action. Diabetes is so difficult to treat, said Anne Peters Harmel, M.D., professor of medicine, Keck School of Medicine, University of Southern California, Los Angeles, because patients take as many as nine different medications due to their increased risk for heart disease and stroke. A leading risk factor associated with these conditions is elevated triglyceride levels.

Harmel, who is also director of clinical diabetes programs at the University of Southern California, was one of the authors of the Impact of Pioglitazone and Rosiglitazone on Risk Factors for Cardiovascular Disease (IMPROVE) study. IMPROVE was a retrospective chart review study to evaluate the effect of adding either pioglitazone (Actos, Takeda Pharmaceuticals) or rosiglitazone (Avandia, GlaxoSmithKline) to metformin in patients with Type 2 diabetes, she said. The primary endpoint of the study was a change in triglyceride levels.

Patients received either pioglitazone and metformin or rosiglitazone and metformin, said Harmel. Persons who received pioglitazone and metformin had a highly statistically significant decrease in their triglyceride levels (48.0 mg/dL, or 19.8% from baseline) compared with those taking rosiglitazone and metformin, she reported. Those in the rosiglitazone group actually had an increase of 22.0 mg/dL (or 10.8% from baseline) in their triglyceride levels.

"These findings are particularly significant because of the link between diabetes and heart disease," said Harmel. "Diabetes dramatically increases the risk of heart disease and stroke. It is important that we learn which therapies can potentially minimize that risk by improving clinical factors for heart disease."

"These results suggest that pioglitazone and rosiglitazone differ from one another in terms of effects on lipids," Harmel continued, "and that pioglitazone may actually provide additional cardiovascular benefits. That cannot be definitely determined, however, until outcomes data are available, which will not be for a long time. Although decreases in triglycerides are a marker for something better, it does not prove a difference in outcomes."

Sales of single-pill combination drug therapies will increase at a rate of 24% annually, capturing 16% of the Type 2 diabetes market by 2011, according to Decision Resources, a research and advisory firm focusing on pharmaceutical and healthcare issues. Said Carole deDios, a Decision Resources analyst, "The Type 2 diabetes market will double to $17.2 billion in 2011, reflecting annual growth of 7% from 2001 through 2011. Much of this growth will be from single-pill combinations, which improve ease of dosing."

Charlotte LoBuono

Charlotte LoBuono. Single-pill combinations: New therapy for Type 2 diabetes.

Drug Topics

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