Restoring Insulin Secretion - Adult Medication Study (RISE Adult Medication)
Number of Subjects in Study Archive: 267
Study Design: Interventional
Conditions: Diabetes Mellitus, Type 2, Prediabetic State
Duration: April 2013 – August 2019
# Recruitment Centers: 3
Treatment: Metformin, Liraglutide, Glargine
Available Genotype Data: No
Image Summary: No
Transplant Type: None
Does it have dialysis patients: No
Clinical Trials URL: https://clinicaltrials.gov/ct2/show/NCT01779362
Approximately 10 percent of Americans have diabetes and at least 33 percent of American adults are considered prediabetic. The increasing loss of beta-cell function is one of the key factors in the pathogenesis of type 2 diabetes. Over time, increased insulin resistance and beta-cell dysfunction can lead to serious health complications in diabetics. Research efforts have begun to focus on the effects of certain interventions on insulin resistance and beta-cell function at the early stages of the disease. The Restoring Insulin Secretion (RISE) Adult Medication Study was established to determine if pharmaceutical treatment could preserve or improve beta-cell function in adults with prediabetes or recent onset type 2 diabetes.
The RISE Adult Medication Study was a partially double-blind, placebo-controlled, four-arm clinical trial. Study participants were randomized into four groups and received treatment for 12 months. During the treatment period, the first group received Metformin alone; the second group received Glargine for three months, followed by Metformin for the remaining nine months; the third group received Liraglutide in combination with Metformin; and the fourth group was treated with placebo. Following the 12-month treatment period, each group underwent treatment withdrawal for three months. Insulin sensitivity and beta-cell function was evaluated at baseline, the end of the treatment period, and the end of the withdrawal period.
The purpose of the RISE Adult Medication Study was to determine if pharmacologic intervention could sustain or enhance beta-cell function in adults who were prediabetic or recently diagnosed with type 2 diabetes, and if the effects could be maintained after treatment withdrawal.
Primary Outcome Measure:
After 15 months, which consisted of 12 months of active treatment followed by three months of therapy withdrawal, beta-cell function and insulin sensitivity were assessed in study participants and compared to baseline assessments.
Secondary Outcome Measures:
Beta-cell function and glucose tolerance were measured at the end of the 12-month active treatment period and compared to baseline measurements.
Study participants were age 20 – 65 years; had diabetes for less than one year; had no prior insulin or other glucose lowering agents; body mass index 25 – 50 kg/m2; and met the glucose-based parameters (HbA1c ≤7.0%, as well as fasting plasma glucose 95-125 mg/dl and OGTT 2-hour glucose ≥140 mg/dl).
Individuals were excluded from participation if they had cardiovascular disease or another condition that would prevent them from safely undergoing clamp studies; serum potassium abnormality or renal disease; anemia or coagulopathy; active infections; underlying disease or condition that would increase the risk of intervention, limit life span, or limit participation in outcomes assessment; had an underlying disease (other than type 2 diabetes) that affects glucose metabolism; taking or needing medication that affects glucose metabolism; a history of conditions that could be negatively impacted by the study drug; or they had behaviors or conditions that could impede study procedures.
After the 12-month treatment period, the three active treatment groups showed improvements in glucose-stimulated beta-cell responses compared to baseline measurements. The group that received Liraglutide combined with Metformin had the most significant improvements in beta-cell responses. However, the assessments that were conducted at the end of the withdrawal period indicate the treatment benefits didn’t persist after withdrawal. These findings suggest that continual treatment may be necessary in order to improve or maintain beta-cell function in adults with prediabetes or in the early stages of type 2 diabetes.