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03-06-2010 | Diabetes | Article

Low-dose rosiglitazone plus metformin prevents Type 2 diabetes in at-risk patients


Free abstract

MedWire News: Low-dose combination therapy with rosiglitazone and metformin is effective for preventing the onset of Type 2 diabetes in patients with impaired glucose tolerance (IGT), show results from the CANOE trial.

“These results lend support to the notion of use of low-dose combination therapies as an effective means to manage complex metabolic disorders,” say the researchers.

Writing in The Lancet, Bernard Zinman (University of Toronto, Ontario, Canada) and colleagues report results from the CANOE (CAnadian Normoglycemia Outcomes Evaluation) trial.

In total, 207 individuals with IGT, aged 52.5 years on average, were randomly assigned to receive a combination of rosiglitazone 2 mg and metformin 500 mg twice daily (n=103) or matching placebo (n=104). They were followed up for a median period of 3.9 years for incident Type 2 diabetes.

Zinman and team found that incident diabetes was significantly more common in the placebo than in the treatment group, at 39% versus 14%.

Treatment with the combination of rosiglitazone and metformin achieved a reduction in relative and absolute risk for incident Type 2 diabetes of 66% and 26%, respectively, which corresponds to a number needed to treat of 4.

Moreover, 80% of the treatment group had returned to normal glucose status by the end of the study compared with only 53% of the placebo group.

Insulin sensitivity was unchanged in the treatment group, but decreased in the placebo group over the follow-up period. Change in β-cell function over the study period did not differ significantly between the two groups.

Side effects were generally minimal. No cases of myocardial infarction or heart failure were recorded in the treatment group, with one of each recorded in the placebo group. Incidence of bone fracture was similar in the treatment and placebo groups, as was the likelihood of gain or loss of 2–3 kg in weight.

“Low-dose combination therapy with rosiglitazone and metformin was highly effective in prevention of Type 2 diabetes in patients with impaired glucose tolerance, with little effect on the clinically relevant adverse events of these two drugs,” conclude the authors.

The authors of an accompanying commentary, Thomas Buchanan and Anny Xiang (University of Southern California, Los Angeles and Kaiser Permanente, Pasadena, USA), suggest: “We need data on more intensive approaches, including high-dose combination therapy, to provide clinicians with a full range of evidence-based approaches to halt or reverse this progressive disease relatively early in its course.”

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Helen Albert