Preserving Beta-cell Function in Type 2 Diabetes With Exenatide and Insulin (PREVAIL)

What Was Tested

This registered phase 3 trial tested Exenatide.

Type 2 diabetes mellitus is a chronic metabolic disorder characterized by progressive deterioration in the function of the pancreatic beta-cells, which are the cells that produce and secrete insulin (the hormone primarily responsible for the handling of glucose in the body).

The investigators propose a randomized controlled trial to determine whether combining basal insulin with a new medication called exenatide is a therapeutic strategy that can preserve beta-cell function early in the course of type 2 diabetes.

It had three arms (groups): Basal insulin and exenatide (experimental), Basal insulin only (active comparator) and Basal Insulin and bolus insulin (active comparator).

Participants in this arm will undergo an 8-week course of treatment with glargine sc injection at bedtime, titrated to target fasting glucose.

Participants in this arm will undergo an 8-week course of multiple daily insulin injection therapy, consisting of titrated basal insulin glargine at bedtime and insulin lispro before each meal.

The registry classes the interventions as drug.

More on the Plan

They will then go into a 12-week washout on lifestyle modification only.

Beta-cell function will be assessed by determining the Insulin Secretion-Sensitivity Index-2 (ISSI-2) on oral glucose tolerance test (OGTT) performed at baseline, 4-weeks, 8-weeks, and 20-weeks.

The primary outcome will be mean beta-cell function (ISSI-2) over the 8-week treatment period.

Who Took Part

Enrollment: 105 actual participants took part.

It was open to people of any sex aged from 30 years up to 80 years.

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

Examples of who could join: Men and women between the ages of 30 and 80 years inclusive. T2DM diagnosed by a physician ≤7 years prior to enrolment. BMI ≥ 23 kg/m2. Negative pregnancy test at recruitment for all women with childbearing potential.

The full record lists 6 inclusion and 12 exclusion criteria; among the exclusions: current anti-diabetic treatment with insulin or a glucagon-like peptide-1 (glp-1) agonist; type 1 diabetes or secondary forms of diabetes; history of hypoglycemia unawareness or severe hypoglycemia requiring assistance.

How the Study Was Run

Design: randomized, parallel-group and open-label.

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

Groups ran in parallel: each of the participants stayed in one arm throughout.

Being open-label, the Exenatide study did not mask who received what.

It started in 2014-09 with completion listed for 2021-12.

It ran at 1 site in Canada.

Its stated primary purpose is treatment.

What Was Measured

Primary outcome: Mean beta-cell function over the 8-week treatment period, measured using the Insulin Secretion-Sensitivity Index-2 (ISSI-2) (time frame: 8 weeks).

It also tracked 4 secondary outcomes, for example Baseline-adjusted beta-cell function at 20 weeks, Baseline-adjusted glycemic control at 20 weeks, Endothelial function at 8 weeks and Baseline-adjusted glycemic control at 8 weeks.

What This Means in Plain Language

Put simply, this is a phase 3, randomized trial of Exenatide in 105 people.

The trial is marked completed; no results are posted to the registry yet, so nothing here describes outcomes.

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