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

Abstract：

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.

journal_name

Diabetes Care

journal_title

Diabetes care

authors

RISE Consortium.

doi

10.2337/dc18-0787

subject

Has Abstract

pub_date

2018-08-01 00:00:00

pages

1717-1725

issue

eissn

0149-5992

issn

1935-5548

pii

dc18-0787

journal_volume

pub_type

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