Antidiabetic Effects of Adding a DPP-4 Inhibitor to Pre-Existing Treatment With an Incretin Mimetic in Patients With T2D

What Was Tested

The trial (phase 3) is built around Liraglutide.

Objectives: To quantify differences in control of glycemia (primary objective) and the secretion of endogenous incretin hormones (secondary objective) comparing sitagliptin or placebo added to pre-existing therapy with liraglutide and metformin.

It had two arms (groups): Sitagliptin, then Placebo (experimental) and Placebo, then Sitagliptin (experimental).

The registry classes the interventions as drug and other.

More on the Plan

This is a double blind, controlled, cross-over comparison of adding sitagliptin (or placebo) to pre-existing metformin+liraglutide therapy.

At the end of this 2 weeks therapy, a mixed meal challenge will take place, with the assessment of glucose and hormone responses (insulin, C-peptide, glucagon, GLP-1 \[glucagon-like peptide-1\], GIP (gastric inhibitory peptide) and gastric emptying as measured by 13C (carbon 13)-octanoate breath tests.

Who Took Part

16 actual participants took part.

It was open to people of any sex aged from 25 years up to 75 years.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: Signed \& dated written informed consent. Male \& female subjects with a diagnosis of type 2 diabetes mellitus according to ADA criteria at least 4 months prior to screening. Medical history without major pathology (with the exception of type 2 diabetes) as judged by the investigator. Age: 25 - 75 years, both inclusive. Body mass index (BMI): 22 - 40kg/m\^2, both inclusive.

The full record lists 8 inclusion and 27 exclusion criteria; among the exclusions: subjects with type 1 diabetes, maturity onset diabetes of the young (mody) or secondary forms of diabetes such as due to pancreatitis; treatment with any hypoglycaemic medication other than metformin and liraglutide within one month prior to screening; known of diabetic gastroparesis and / or prokinetic therapy.

How the Study Was Run

The set-up was randomized, crossover and double-blind.

Random assignment meant chance, not the researchers, decided who got Liraglutide and who got the comparison, which limits bias.

In the crossover set-up each of the participants took both Liraglutide and the comparison in turn, acting as their own control.

Blinding on both sides kept the participants and researchers unaware of who received Liraglutide.

Those kept unaware of assignments: participant and investigator.

It started in 2013-08 with completion listed for 2014-04.

It ran at 1 site in Germany.

Its stated primary purpose is basic science.

What Was Measured

Primary outcome: Incremental Area Under the Plasma Glucose (BG) Concentration-time Profile (AUC) (time frame: 0 to 300 min post mixed meal test).

It also tracked 8 secondary outcomes, for example AUC Plasma Glucose, AUC Insulin, AUC C-peptide, AUC Glucagon, AUC Total GLP-1 and AUC Total GIP.

What This Means in Plain Language

Put simply, this is a phase 3, randomized trial of Liraglutide in 16 people.

Its size is small, so on its own it can only give an early look.

The trial is marked completed; results are posted on the registry, and this page does not restate them.

More context: the Liraglutide compound page, all human trials.