BOSTON — The addition of the dipeptidyl-peptidase-4 (DPP-4) inhibitor sitagliptin provided no added benefit in patients with diabetes who were being treated with the glucagon-like peptide (GLP-1) receptor agonist liraglutide, according to data presented at the American Diabetes Association (ADA) 75th Scientific Sessions.

“Both GLP-1 receptor agonists and DPP-4 inhibitors are incretin-based drugs. That, in the end, should at least partly explain the mechanism of action by an increased stimulation of GLP-1 receptors,” Michael A. Nauck, MD, of St. Josef Hospital in Bochum, Germany, said during his presentation.

It is unknown, however, whether co-administration of agents from both classes leads to more glucose-lowering effects. Therefore, Nauck and colleagues sought to study this more formally and mechanistically.

In their study, the researchers evaluated 16 patients with type 2 diabetes (5 women, 11 men) with a mean age of 55 years and BMI of 31.7. Mean duration of diabetes was 9.4 years, metformin dose was 2,044 mg daily and HbA1c was 7.5%. At the time, patients were treated with metformin and liraglutide 1.2 mg daily, and were then randomly assigned sitagliptin or placebo. 

Glucose excursions after a mixed meal served as the primary endpoint, with researchers also looking at insulin secretion, C-peptide, glucagon, GLP-1 and total and intact gastric inhibitory polypeptide (GIP).

The researchers assessed patients after an overnight fast, in randomized order, with sitagliptin 100 mg p.o. or matched placebo given 60 minutes before consumption of a standard mixed meal.

Sitagliptin appeared to augment meal-induced responses of GLP-1 by 78.4% and GIP by 90.2% (P<.0001). Total GLP-1 and GIP responses were decreased by 36.5% and 18.2%, respectively.

Results showed that sitagliptin did not significantly affect insulin, C-peptide, glucagon and glucose concentrations (P=.60-1.00). This is “most likely because GLP-1 receptors are maximally stimulated by liraglutide alone,” according to the researchers.

Sitagliptin’s influence on incretin plasma concentrations were on par with those seen in patients with type 2 diabetes on metformin alone.

“Co-administration of a GLP-1 receptor agonist and a DPP-4 inhibitor does not improve glycemic results compared to a GLP-1 receptor agonist alone,” Nauck said. “Our results do not support the use of a GLP-1 receptor agonist and a DPP-4 inhibitor in combination.”

Reference

  1. Nauck MA et al. Abstract 10-OR: Adding a DPP-4 Inhibitor to Ongoing Therapy with a GLP-1 Receptor Agonist and Metformin Increases Intact GLP-1, But Does Not Change Insulin or Glucagon Secretion nor Plasma Glucose Excursions following a Mixed Test Meal in Patients with Type 2 Diabetes. Presented at: American Diabetes Association (ADA) 75th Scientific Sessions; June 5-9, 2015; Boston.