Weight loss and β-cell responses following gastric banding or pharmacotherapy in adults with impaired glucose tolerance or type 2 diabetes: a randomized trial

Obesity (Silver Spring). 2022 Aug;30(8):1579-1588. doi: 10.1002/oby.23475.


Objective: The extent to which weight loss contributes to increases in insulin sensitivity (IS) and β-cell function after surgical or medical intervention has not been directly compared in individuals with impaired glucose tolerance or newly diagnosed type 2 diabetes.

Methods: The Restoring Insulin Secretion (RISE) Study included adults in the Beta-Cell Restoration Through Fat Mitigation Study (n = 88 randomized to laparoscopic gastric banding or metformin [MET]) and the Adult Medication Study (n = 267 randomized to placebo, MET, insulin glargine/MET, or liraglutide + MET [L + M]). IS and β-cell responses were measured at baseline and after 12 months by modeling of oral glucose tolerance tests and during arginine-stimulated hyperglycemic clamps. Linear regression models assessed differences between and within treatments over time.

Results: BMI decreased in all treatment groups, except placebo, at 12 months. IS increased in all arms except placebo and was inversely correlated with changes in BMI. L + M was the only treatment arm that enhanced multiple measures of β-cell function independent of weight loss. Insulin secretion decreased in the laparoscopic gastric banding arm proportional to increases in IS, with no net benefit on β-cell function.

Conclusions: Reducing demand on the β-cell by improving IS through weight loss does not reverse β-cell dysfunction. L + M was the only treatment that enhanced β-cell function.

Trial registration: ClinicalTrials.gov NCT01779362 NCT01763346.

Publication types

  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Blood Glucose
  • Diabetes Mellitus, Type 2* / diagnosis
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / surgery
  • Gastroplasty*
  • Glucose Intolerance* / drug therapy
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Insulin / therapeutic use
  • Insulin Resistance* / physiology
  • Metformin* / pharmacology
  • Metformin* / therapeutic use
  • Weight Loss


  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Metformin

Associated data

  • ClinicalTrials.gov/NCT01779362
  • ClinicalTrials.gov/NCT01763346