American Diabetes Association

Conference summaries


Results and Comparisons from the RISE Clinical Trial—Adult Medication Study

Presented by: David A. Ehrmann, MD
The University of Chicago, Chicago, IL, USA
Kieren J. Mater, MD
Indiana University School of Medicine, Indianapolis, IN, USA
Sharon Edelstein, ScM
George Washington University, Washington, DC, USA
Steven E. Khan, MD, ChB
VA Puget Sound Health Care System, Seattle, WA, USA
Thomas A. Buchanan, MD
University of Southern California, Los Angeles, CA, USA
Sonia Caprio, MD
Yale University School of Medicine, New Haven, CT, USA
  • Progression from prediabetes to type 2 diabetes is driven by ongoing worsening of b-cell secretory function in the setting of insulin resistance.
  • Restoring ß-cell function is of primary clinical interest.

Prior research has demonstrated that interventions targeting improvements in b-cell function and/or insulin sensitivity can be effective in slowing or reversing progressive loss of glycemic control. The Restoring Insulin Secretion (RISE) Adult Medication Study asked the question of whether β-cell function be preserved or improved during 12 months of pharmacologic intervention, and maintained for 3 months following the withdrawal of therapy, in adults with impaired glucose tolerance (IGT) or recently diagnosed type 2 diabetes.

  • RISE compared pharmacological approaches targeted to improve ß-cell function in individuals with IGT or treatment-naive type 2 diabetes of <12 months duration.

Type of study, patients, and inclusion criteria

  • A total of 267 adults with IGT (n=197, 74%) or recently diagnosed type 2 diabetes (n=70, 26%) were studied.
  • Participants were randomized to one of three groups.
  • Blinded metformin alone and matched placebo:
    • Metformin titrated over 4 weeks from 500 mg/day to 1,000 mg BID.
  • Liraglutide + metformin:
    • Liraglutide titrated over 4 weeks from 0.6 mg/day to 1.8 mg/day.
    • Metformin titrated as above after liraglutide dose stable.
  • Glargine followed by metformin:
    • Once daily insulin glargine, titrated twice weekly over one month based on SMBG to goal of 80-90 mg/dL fasting blood glucose level.
    • Glargine discontinued and metformin titrated after 3 months.
  • ß-cell function was assessed using hyperglycemic clamps at baseline, 12 months (on treatment), and 15 months (3 months off treatment).

Primary outcome measure

  • The primary outcome was ß-cell function at 15 months compared with baseline.
  • All three active treatments produced on-treatment reductions in weight and improvements in HbA1c compared with placebo, with the greatest reductions in the liraglutide plus metformin group.
  • At 12 months, glucose-stimulated C-peptide responses improved in the three active treatment groups and were greatest in the liraglutide plus metformin group, but the arginine-stimulated incremental C-peptide response was reduced in the liraglutide plus metformin group.
  • Despite on-treatment benefits, 3 months after treatment withdrawal there were no sustained improvements in ß-cell function in any treatment group.
  • See Figure.


  • In adults with IGT or recently diagnosed type 2 diabetes, interventions that improved ß-cell function during active treatment failed to produce persistent benefits after treatment withdrawal.

Key Messages/Clinical Perspectives

  • Continued intervention may be required to alter progressive ß-cell dysfunction in IGT or early type 2 diabetes.


Trial: NCT01779362



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 Jun;dc190556.

Present disclosure: D.A. Ehrmann, S. Edelstein, S. Caprio: the presenters has reported that no relationships exist relevant to the contents of this presentation. K.J. Mater: Roche, Abbott, Merch & Co. Inc., Novo Nordisk A/S, Sanofi. K.E. Khan: Boehringer Ingelheim, Eli Lilly, Intarcia, Janssen, Merck & Co., Novo Nordisk A/S, Neurimmune. T.A. Buchanan: Allergan, Apollo EndoSurgery.

Written by: Patrick Moore, PhD

Reviewed by: Marco Gallo, MD

All report

Welcome to the ADA 2019 Highlights

Jose C. Florez, MD, PhD
Chair, ADA Scientific Sessions Meeting Planning Committee
The 79th American Diabetes Association’s Scientific Sessions were held in San Francisco, California from June 7-11, 2019. The meeting was attended by over 15,000 professional attendees from 115 countries, … [ Read all ]



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Results and Comparisons from the RISE Clinical Trial—Adult Medication Study

Presented by: David A. Ehrmann, MD; Kieren J. Mater, MD; Sharon Edelstein, ScM; Steven E. Khan, MD, ChB; Thomas A. Buchanan, MD; Sonia Caprio, MD



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