No superior third drug for hyperglycaemia

NO ANTIHYPERGLYCAEMIC drug class is superior to any other when added as a third agent in patients with type 2 diabetes, a meta-analysis shows.

Brazilian researchers looked at the efficacy of add-on anti­hyperglycaemic agents in patients not controlled on metformin and sulphonylurea, analysing 18 trials involving 4500 patients.

They found that HbA1c was reduced by 0.9% when a third agent was added, but it didn’t matter if it was insulin, thiazolidinediones, acarbose, glucagon-like peptide-1 (GLP-1) agonists or DPP-4 inhibitors.

Acarbose resulted in the lowest decrease in HbA1c at 0.7% and insulin caused the greatest decrease in HbA1c at 1.08%.

However, insulin caused a 2.8 kg increase in weight, and thiazolidinediones a 4.3 kg increase, compared with a 1.6 kg weight loss with GLP-1 agonists.

Insulin also caused around twice as many severe hypoglycaemic incidences as the other agents.

“When choosing a third drug… the patient’s clinical features, such as importance of weight changes and incidence of hypoglycaemia, should be taken into account,” the authors said. 

Endocrinologist Professor Don Chisholm, from the Garvan Institute of Medical Research in Sydney, said no guidelines advised a particular third agent.

There was no long-term data on glycaemic outcomes for DPP-4 inhibitors or GLP-1 agonists.

“What we do have is that thiazolidinediones possibly would have the best long-term glycaemic control outcomes but the fluid retention and weigh gain is an adverse issue,” he said.

Ann Intern Med 2011; 154:672-79