Restoring Insulin Secretion Study (RISE)

The primary questions asked by RISE are, in participants with IGT or recently diagnosed type 2 diabetes:

Pediatric and Adult Medication Studies

Can β-cell function be preserved or improved during 12 months of active treatment and maintained for 3 months following the withdrawal of therapy?

Adult Surgery Study

Can β-cell function be preserved or improved 24 months following laparoscopic banding weight loss surgery?

The 3 RISE Studies are:

1) The RISE Adult Medication Study is a 4-arm clinical trial in adults with prediabetes and early type 2 diabetes. A total of 267 adult participants (ages 20-65) were randomized to (1) metformin alone, (2) insulin glargine followed by metformin, (3) liraglutide plus metformin, or (4) placebo. The main study results will be presented at the American Diabetes Association (ADA) and simultaneously published in June 2019.

2) The RISE Pediatric Medication Study is a 2-arm clinical trial in youth with prediabetes and early type 2 diabetes. A total of 91 pediatric participants (ages 10-19) were randomized to either: (1) insulin glargine followed by metformin or (2) metformin alone. The main study results were presented at the ADA and simultaneously published in June 2018, and at the European Association for the Study of Diabetes (EASD) in October 2018.

3) The Adult Surgery Study (BetaFat) is a 2-arm clinical trial in adults with prediabetes and early, drug-naive, type 2 diabetes. A total of 88 adult participants (ages 22-65) were randomized to gastric banding or metformin. The primary study results were presented at the EASD and simultaneously published in October 2018.

VISIT STUDY WEBSITE

BSC INVESTIGATORS

Sharon Edelstein

ADDITIONAL INVESTIGATOR(S)

John Lachin

RESEARCH STAFF

Ashley Hogan Tjaden

Mark Tripputi

Laure El ghormli

MAJOR PUBLICATIONS

The RISE Consortium. Lack of Durable Improvements in β-Cell Function Following Withdrawal of Pharmacological Interventions in Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes. Diabetes Care 2019 Sep;42(9):1742-1751. dc190556; DOI: 10.2337/dc19-0556. PMID: 31178434. PMCID: PMC6702605. PubMed

The RISE Consortium. Effects of Treatment of Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes With Metformin Alone or in Combination With Insulin Glargine on β-Cell Function: Comparison of Responses In Youth And Adults. Diabetes 2019 Aug;68(8):1670-1680; db190299. https://doi.org/10.2337/db19-0299. PMID: 31178433. PMCID: PMC6692818. PubMed.

RISE Consortium. Impact of Insulin and Metformin versus Metformin along on β-Cell Function in Youth with Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes. Diabetes Care. Diabetes Care Aug 2018; 41 (8): 1717-1725.

Xiang AH, Trigo E, Martinez M, Katkhouda N, Beale E, Wang X, Wu J, Chow T, Montgomery C, Nayak K, Hendee F, Buchanan T, RISE Consortium. Impact of Gastric Banding Versus Metformin on β-Cell Function in Adults With Impaired Glucose Tolerance or Mild Type 2 Diabetes. Diabetes Care 2018; 41(12): 2544-2551.

RISE Consortium. Metabolic Contrasts between Youth and Adults with Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes: I. Observations Using the Hyperglycemic Clamp. Diabetes Care 2018; 41 (8): 1696-1706.

RISE Consortium. Metabolic Contrasts between Youth and Adults with Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes: II. Observations Using the Oral Glucose Tolerance Test. Diabetes Care 2018; 41 (8): 1707-1716.

Additional Publications

RISE Consortium. Restoring Insulin Secretion (RISE): Design of studies of β-cell preservation in prediabetes and early type 2 diabetes across the life span. Diabetes Care 2014; 37 (3):780-8.

Hannon TS , Kahn SE , Utzschneider KM , Buchanan TA , Nadeau KJ , Zeitler PS , Ehrmann DA, Arslanian SA , Caprio S , Edelstein SL , Savage PJ , Mather KJ ; for the RISE Consortium. Review of methods for measuring β-cell function: Design considerations from the Restoring Insulin Secretion (RISE) Consortium. Diabetes Obes Metab. 2018;20:14–24.

RISE includes 3 randomized clinical trials examining whether aggressive glucose lowering will lead to recovery of pancreas function (β-cell function) in adults and youth with impaired glucose tolerance (IGT) and early type 2 diabetes.

Adult Medication Study:
•   Insulin resistance and β-cell dysfunction in adults with obesity with IGT or early type 2 diabetes were significantly improved by liraglutide+metformin, and moderately responsive to metformin alone or glargine following metformin.
•   Three months after withdrawal of the intervention, β-cell function returned to baseline levels in all groups.
•   While improvement in β-cell function in the liraglutide+metformin arm was significantly higher than in the other groups after 12 months of treatment, there were no significant difference in β-cell function by treatment group following 3 months of washout.

Pediatric Medication Study:
•   Insulin resistance and β-cell dysfunction in obese youth with IGT or early type 2 diabetes were unresponsive to metformin alone or glargine followed by metformin.
•   Three months after withdrawal of the intervention, β-cell dysfunction progressed and was worse than at baseline.
•   There were no significant differences in β-cell function by treatment group after 12 months of active treatment or following 3 months of washout.

Adult Surgery Study:
•   Insulin resistance and β-cell function in obese adults with IGT or early type 2 diabetes were unresponsive to metformin alone or lap band surgery.
•   After two years of lap band surgery or metformin use, β-cell dysfunction progressed and was worse than at baseline.
•   There were no significant differences in β-cell function by treatment group after two years of active treatment.

NIDDK