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15-04-2010 | Diabetes | Article

Add-ons to metformin produce similar glycemic effects, but differing side-effects


Free abstract

MedWire News: All noninsulin antidiabetic drugs reduce glycated hemoglobin (HbA1c) to a similar degree when added to the maximum dose of metformin, but have differing effects on body weight and risk for hypoglycemia, show study results.

“Metformin is the recommended initial drug therapy for patients with Type 2 diabetes mellitus,” write Craig Coleman (University of Connecticut, Hartford, USA) and colleagues in the Journal of the American Medical Association.

“However, the optimal second-line drug when metformin monotherapy fails is unclear.”

To investigate this further, Coleman and team carried out a systematic review and meta-analysis of 27 randomized controlled trials involving a total of 11,198 participants.

To be included, trials had to be of at least 3 months’ duration (mean duration 32 weeks) and provide data on the efficacy of noninsulin antidiabetic drugs in Type 2 diabetic patients inadequately controlled on maximized metformin therapy.

The researchers compared the ability of the add-on drugs to reduce HbA1c, allow patients to achieve an HbA1c of less than 7%, change body weight, and induce hypoglycemia.

The different classes of add-on drugs produced similar reductions in HbA1c, ranging from 0.64–0.97%, compared with placebo. In addition, patients who took all classes of noninsulin antidiabetic drugs were significantly more likely to achieve an HbA1c of less than 7% than placebo.

Patients who took thiazolidinediones, sulfonylureas, and glinides gained 1.77–2.08 kg in weight. In contrast, those who took glucagon-like peptide-1 analogs, α-glucosidase inhibitors, and dipeptidyl peptidase-4 inhibitors either had no change in weight or lost up to 1.80 kg.

Regarding hypoglycemia, those who took sulfonylureas and glinides were 4.57- and 7.50-fold more likely to experience hypoglycemia than placebo, respectively, whereas patients who took other noninsulin antidiabetic drugs did not have a significantly increased risk for hypoglycemia compared with placebo.

Coleman et al conclude: “These factors and other considerations should be taken into account when selecting a second-line treatment to add to stable, maximum metformin therapy.”

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