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02-05-2012 | Cardiology | Article

Benefits of recommended Type 2 diabetes therapy dubious


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MedWire News: Patients with Type 2 diabetes do not necessarily have improved outcomes if they take a combination of metformin and insulin instead of insulin alone, report researchers.

Although metformin combined with insulin seems to cause favorable reductions in glycated hemoglobin (HbA1c), weight, and insulin doses compared with insulin alone, there is no evidence for improved all-cause or cardiovascular mortality with the combination regimen, they say.

"This lack of evidence means that possible harm cannot be excluded according to current criteria," they warn.

Led by Bianca Hemmingsen (Copenhagen University Hospital, Denmark), the team conducted a systematic review of 23 clinical trials to compare the benefits and harms of metformin and insulin versus insulin alone in 2117 individuals. All trials included interventions of at least 12 weeks duration.

The researchers assessed data for bias risk across the following domains: generation of the allocation sequence, allocation concealment, blinding of investigators and participants, blinding of outcomes assessors, incomplete outcome data, selective outcome reporting, and other sources of bias. Trial sequential analysis was conducted to decide whether the studies obtained sufficiently low p-values to show reliable effects.

The researchers report that metformin and insulin versus insulin alone did not significantly affect all-cause mortality or cardiovascular mortality, at relative risks of 1.30 and 1.70, respectively. However, trial sequential analysis showed that only 2.93% and 0.65%, respectively, of the required amount of data was accrued to reliably establish these effects.

In addition, all trials had a high risk for bias and only two were considered to have a low risk for bias, report the authors.

"This finding could lead to a systematic overestimation of beneficial effects and an underestimation of adverse effects," remarks the team.

In a random effects model, insulin dose, weight and HbA1c were significantly reduced with the combination of metformin and insulin compared with insulin alone, and trial sequential analysis showed that sufficient evidence was available to support these conclusions.

However, "these variables are, at best, unvalidated surrogate indicators of a potentially reduced risk for microvascular and macrovascular complications," write the researchers in the BMJ.

"The incomplete evidence on patient relevant outcomes is surprising, in view of current international consensus statements on diabetes clearly recommending the use of metformin and insulin in almost all patients with Type 2 diabetes," remark Hemmingsen et al.

By Sally Robertson

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