Impact of Insulin and Metformin Versus Metformin Alone on β-Cell Function in Youth With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes

Diabetes Care. 2018 Aug;41(8):1717-1725. doi: 10.2337/dc18-0787. Epub 2018 Jun 25.


Objective: Pediatric type 2 diabetes prevalence is increasing, with β-cell dysfunction key in its pathogenesis. The RISE Pediatric Medication Study compared two approaches-glargine followed by metformin and metformin alone-in preserving or improving β-cell function in youth with impaired glucose tolerance (IGT) or recently diagnosed type 2 diabetes during and after therapy withdrawal.

Research design and methods: Ninety-one pubertal, overweight/obese 10-19-year-old youth with IGT (60%) or type 2 diabetes of <6 months duration (40%) were randomized to either 3 months of insulin glargine with a target glucose of 4.4-5.0 mmol/L followed by 9 months of metformin or to 12 months of metformin alone. β-Cell function (insulin sensitivity paired with β-cell responses) was assessed by hyperglycemic clamp at baseline, 12 months (on treatment), and 15 months (3 months off treatment).

Results: No significant differences were observed between treatment groups at baseline, 12 months, or 15 months in β-cell function, BMI percentile, HbA1c, fasting glucose, or oral glucose tolerance test 2-h glucose results. In both treatment groups, clamp-measured β-cell function was significantly lower at 12 and 15 months versus baseline. HbA1c fell transiently at 6 months within both groups. BMI was higher in the glargine followed by metformin versus metformin alone group between 3 and 9 months. Only 5% of participants discontinued the interventions, and both treatments were well tolerated.

Conclusions: In youth with IGT or recently diagnosed type 2 diabetes, neither 3 months of glargine followed by 9 months of metformin nor 12 months of metformin alone halted the progressive deterioration of β-cell function. Alternate approaches to preserve β-cell function in youth are needed.

Trial registration: NCT01779375.

Publication types

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

MeSH terms

  • Adolescent
  • Age Factors
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Child
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / physiopathology
  • Drug Therapy, Combination
  • Female
  • Glucose Intolerance / drug therapy*
  • Glucose Intolerance / metabolism
  • Glucose Intolerance / physiopathology
  • Glucose Tolerance Test
  • Humans
  • Insulin / administration & dosage*
  • Insulin / adverse effects
  • Insulin Glargine / administration & dosage
  • Insulin Glargine / adverse effects
  • Insulin Resistance / physiology
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / physiology*
  • Male
  • Metformin / administration & dosage*
  • Metformin / adverse effects
  • Young Adult


  • Blood Glucose
  • Insulin
  • Insulin Glargine
  • Metformin

Associated data