Antihyperglycemic agents useful as third agent, but class preference unclear

There is no clear difference in benefit between drug classes when adding an antihyperglycemic as a third agent to the treatment of patients with type 2 diabetes who are already receiving metformin and a sulfonylurea, according to a meta-analysis published in the May 17 issue of Annals of Internal Medicine.

To compare the efficacy of add-on antihyperglycemic drugs in patients with type 2 diabetes that is not controlled with metformin and a sulfonylurea, investigators looked at several data sources for studies that were at least 24 weeks in length and that evaluated the effects of adding a third antihyperglycemic drug to the treatment of adults aged 18 years or older with type 2 diabetes and an HbA_1c level >7.0% who were already receiving the metformin-sulfonylurea combination. The study included 18 trials involving 4,535 participants. Researchers examined the change in HbA_1c level and change in weight before and after interventions, and recorded the frequency of severe hypoglycemia.

Compared with placebo, the results indicated that drug class did not differ in effect on HbA_1c level (reduction ranging from -0.70% [95% credible interval {CrI}, -1.33% to -0.08%] for acarbose to -1.08% [CrI, -1.41% to -0.77%] for insulin). Weight increase was seen with insulins (2.84 kg [CrI, 1.76 to 3.90 kg]) and thiazolidinediones (4.25 kg [CrI, 2.76 to 5.66 kg]), and weight loss was seen with glucagon-like peptide-1 agonists (-1.63 kg [CrI, -2.71 to -0.60 kg]). Insulins caused twice the absolute number of severe hypoglycemic episodes than noninsulin antihyperglycemic agents.

With regard to the outcome of the analysis, it was concluded that, when choosing a third drug to be added to metformin and sulfonylurea therapy in patients requiring additional glycemic control, the patient’s clinical features, such as importance of weight changes and incidence of hypoglycemia, should be taken into account. The most appropriate drug option should be individualized to each patient’s clinical characteristics.