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26-04-2012 | Diabetes | Article

Incretin-based therapy effective as add-on to metformin


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MedWire News: Incretin-based therapy is effective at improving glycemic control when added to metformin treatment in patients with Type 2 diabetes, show study findings.

The results also indicate that within 16 to 30 weeks, significantly greater reductions in glycated hemoglobin (HbA1c) occur with long-acting glucagon-like peptide (GLP)-1 receptor agonists than short-acting ones, or with dipetidyl peptidase (DPP)-4 inhibitors.

The findings come from a meta-analysis of studies evaluating glycemic control, body weight, and adverse events in diabetes patients after 16 to 30 weeks of treatment with different incretin-based add-ons to metformin.

"This is a relevant comparison, because add-on to metformin is a major clinical use for incretin-based therapy," remark Bo Ahrén (Lund University, Sweden) and team.

The analysis included a total of 27 study populations across 21 studies assessing the effects of clinically-recommended doses of exenatide, liraglutide, exenatide long-acting release (LAR), sitagliptin, vildagliptin, saxagliptin, linagliptin, and alogliptin.

As reported in Diabetes, Obesity and Metabolism, incretin-based therapy significantly reduced HbA1c by 0.7-1.3% from baseline levels of 8.0-8.5%.

The reduction in HbA1c was a significant 0.3-0.5% greater with long-acting GLP-1 receptor agonists such as liraglutide or exenatide LAR, than with short-acting exenatide twice-daily or DPP-4 inhibitors. There were no significant differences in HbA1c reduction between exenatide twice-daily and DPP-4 inhibitors.

However, there was a negative correlation between baseline HbA1c and change in HbA1c across the population as a whole, so the magnitude of the effect on HbA1c was dependent on HbA1c baseline value.

The researchers also report that body weight was reduced significantly and to a similar extent with long- and short-acting GLP-1 receptor agonists, but was not significantly altered with DPP-4 inhibitors. There was no correlation between baseline body weight and change in body weight.

The reported numbers of adverse events, including hypoglycemia, were few and comparable to those observed with placebo in those studies that were placebo-controlled. However, GLP-1 receptor agonists were associated with a greater incidence of gastrointestinal side effects and a tendency to increase heart rate compared with DPP-4 inhibitors.

The authors say the findings confirm a previous meta-analysis evaluating the efficacy of incretin-based therapies as reported in published clinical trials.

"It should, however, be emphasized that comparison between different compounds requires head-to-head studies, when various confounding factors can be controlled for, such as baseline HbA1c," note the researchers.

MedWire ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2012

By Sally Robertson

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