RISE Study to Evaluate Liraglutide, Metformin, and Insulin Glargine for Durable Beta-Cell Function Recovery in Prediabetes and Early Type 2 Diabetes

The progression from prediabetes to type 2 diabetes (T2D) is characterized by progressive beta-cell dysfunction and insulin resistance. Current standard-of-care often focuses on glucose control but may not fully address the underlying beta-cell decline, leading to long-term complications. Understanding if intensive glucose-lowering therapies can induce durable recovery of beta-cell function, sustained even after treatment withdrawal, is crucial for developing disease-modifying strategies. This study aims to fill that gap by comparing different therapeutic approaches.

The RISE Adult Medication Study is a 4-arm, 3-center, randomized, controlled clinical trial enrolling adults aged 20-65 with prediabetes and early type 2 diabetes. Participants will be randomized into one of four treatment regimens: (1) blinded placebo, (2) blinded metformin alone, (3) early intensive insulin treatment with basal insulin glargine followed by open-label metformin, or (4) the GLP-1RA liraglutide plus open-label metformin. The active treatment phase will last 12 months, followed by a 3-month post-treatment observation period to assess durability.

The RISE study is designed to address a critical clinical question: Will improvements in ß-cell function observed after 12 months of active treatment be maintained for 3 months following the withdrawal of therapy? The primary endpoint focuses on this durability. Secondary outcomes will assess the sustained nature of glucose tolerance after treatment cessation and identify biomarkers obtained in the fasting state that predict parameters of ß-cell function, insulin sensitivity, and glucose tolerance, as well as the response to the interventions. As an ongoing study, specific results regarding these outcomes are not yet available.