Ideal Add-On to Metformin Therapy Is Still Unclear

A meta-analysis has failed to clarify whether one drug is better than another when added to metformin in patients with type 2 diabetes.

Sulfonylureas and α-glucosidase inhibitors, and possibly glinides, seem to have about equal efficacy when used as add-ons to failed metformin monotherapy, Dr. Matteo Monami and colleagues from the University of Florence (Italy) found in an analysis of 27 clinical trials (Diabetes Res. Clin. Pract. 2008;79:196–203).

Thiazolidinediones seem to have a lesser effect on hemoglobin A_1c (HbA_1c) at 6 months, though in the long term, they may work better than insulin secretagogues.

The authors conducted their Medline search in January 2007, looking for randomized clinical trials in which metformin was associated with any one of a large number of add-on therapies. They included only trials in which a hypoglycemic agent was compared with either placebo or with another active drug in combination with metformin for at least 16 weeks.

They identified 16 placebo-controlled trials and 11 trials in which two active treatments were compared. Of the placebo-controlled trials, five included sulfonylureas, five included α-glucosidase inhibitors, three included thiazolidinediones, two included glinides, and one included GLP-1 agonists. Combining trials for each class of drugs, sulfonylureas reduced HbA_1c by an average of 0.85%, thiazolidinediones by 0.42%, and α-glucosidase inhibitors by 0.61%. After correcting for baseline HbA_1c, the reduction obtained with sulfonylurea with respect to placebo was significantly greater than that of thiazolidinediones. There were no significant differences between sulfonylurea and α-glucosidase inhibitors or between α-glucosidase inhibitors and thiazolidinediones.

Among the trials in which two active agents were compared, sulfonylureas were significantly superior to thiazolidinediones, with an overall difference between the two treatments of 0.17% in reducing HbA_1c. There were no significant differences between sulfonylureas and insulin. Insulin regimens that were based on two administrations of biphasic insulin analogues were more effective than insulin glargine once a day, with an overall difference of 0.26% in reducing HbA_1c.

The researchers had received speaking fees, consultancy fees, and research grants from several pharmaceutical firms.