Low-dose combination therapy to prevent type 2 diabetes mellitus

January 01, 0001

Low-dose combination therapy to prevent type 2 diabetes mellitus

The evolving epidemic of type 2 diabetes has challenged health-care providers to assess the safety and efficacy of various diabetes prevention strategies. The CANOE (CAnadian Normoglycemia Outcomes Evaluation) trial investigated whether low-dose combination therapy would affect development of type 2 diabetes. In this double-blind, randomised controlled trial undertaken in clinics in Canadian centres, 207 patients with impaired glucose tolerance were randomly assigned to receive combination rosiglitazone (2 mg) and metformin (500 mg) twice daily or matching placebo for a median of 3.9 years. Randomisation was computer-generated in blocks of four, with both participants and investigators masked to treatment allocation. 103 participants were assigned to rosiglitazone and metformin, and 104 to placebo; all were analysed. Vital status was obtained in 198 (96%) participants, and medication compliance (taking at least 80% of assigned medication) was 78% (n=77) in the metformin and rosiglitazone group and 81% (n=80) in the placebo group.

Incident diabetes occurred in significantly fewer individuals in the active treatment group (14%) than in the placebo group (39%). The relative risk reduction was 66% and the absolute risk reduction was 26%, yielding a number needed to treat of 4. 80% patients in the treatment group regressed to normal glucose tolerance compared with 53% in the placebo group (significant). Insulin sensitivity decreased by study end in the placebo group and remained unchanged with rosiglitazone and metformin treatment. The change in beta-cell function, as measured by the insulin secretion-sensitivity index-2, did not differ between groups. We recorded an increase in diarrhoea in participants in the active treatment group compared with the placebo group (16% vs 6%; significant).

The researchers concluded: "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."

May be beneficial if rosiglitazone remains around. If so, long-term adverse effects will need to be analyzed.

For the full abstract, click here.

The Lancet 376(9735):103-111, 10 July 2010
© 2010 Elsevier Ltd
Low-dose combination therapy with rosiglitazone and metformin to prevent type 2 diabetes mellitus (CANOE trial): a double-blind randomised controlled study. Bernard Zinman, Stewart B Harris, Jan Neuman et al. Correspondence to Bernard Zinman: [email protected]

Category: T. Endocrine/Metabolic/Nutritional. Keywords: low dose, combination, rosiglitazone, metformin, type 2 diabetes mellitus, CANOE, double-blind randomised controlled study, journal watch.
Synopsis edited by Dr Stephen Wilkinson, Melbourne, Australia. Posted on Global Family Doctor 30 July 2010

Pearls are an independent product of the Cochrane primary care group and are meant for educational use and not to guide clinical care.