BOSTON – Adding a dipeptidyl peptidase-4 (DPP-4) inhibitor to metformin in patients with type 2 diabetes was associated with an increased, earlier need for treatment intensification, compared with adding a sulfonylurea in a large, retrospective, population-based study in the United Kingdom.
Conversely, adding a thiazolidinedione as a second-line glucose-lowering agent resulted in the most durable glycemic response, Jil Mamza reported at the annual scientific sessions of the American Diabetes Association.
Unadjusted survival analysis showed that 23% of 3,080 patients treated with second-line DDP-4 agents experienced treatment failure at 1 year, compared with 15% of 15,508 on a sulfonylurea, and 8% of 1,582 on a thiazolidinedione. The corresponding failure rates at 2 years were 38%, 26% and 12%, said Mr. Mamza, a clinical researcher and doctoral student at the University of Nottingham, Derby, England.
After multivariate adjustment, adding a DPP-4 inhibitor was associated with an increased hazard of intensification of therapy (adjusted hazard ratio, 1.58), while adding a thiazolidinedione was associated with a reduced hazard (adjusted HR, 0.45).
Several baseline factors were also shown to be associated an increased hazard of intensification, including hemoglobin A1c level, diabetes duration, gender, smoking status, and the use of lipid-lowering medications, he said.
Patients included in this study were adults with a mean age of 60 years and a mean disease duration of 3 years from the The Health Initiative Network (THIN) database of United Kingdom general practice patients. All those included had added a second oral glucose lowering therapy (GLT) to metformin between 2007 and 2014.
Time to dual therapy failure was defined as time to treatment substitution or intensification with a third agent at an HbA1c level greater than 58 mmol/mol.
The durability of glycemic response for different second-line treatments was previously unclear. These findings suggest that DPP-4 agents provide the least durable response, compared with sulfonylureas and thiazolidinediones as second-line GLTs, Dr. Mamza said.
Mr. Mamza reported having no disclosures.