Impact of Insulin and Metformin Versus Metformin Alone on β-Cell Function in Youth With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes
Author:
, Nadeau Kristen J.1, Hannon Tamara S.1, Edelstein Sharon L.1ORCID, Arslanian Silva A.1, Caprio Sonia1, Leschek Ellen W.1, Zeitler Philip S.1, Buchanan Thomas A.1, Ehrmann David A.1, Mather Kieren J.1, Kahn Steven E.1, Gross Susan1, Williams Jayne1, Cree-Green Melanie1, Reyes Yesenia Garcia1, Vissat Krista1, Brown Kathleen1, Guerra Nancy1, Porter Kristin1, Savoye Mary1, Pierpont Bridget1, Garrett Tammy1, Lteif Amale1, Patel Aniket1, Chisholm Robin1, Moore Karen1, Pirics Vivian1, Pratt Linda1, Temple Karla A.1, Rue Abby1, Barengolts Elena1, Mokhlesi Babak1, Van Cauter Eve1, Sam Susan1, Miller M. Annette1, Atkinson Karen M.1, Palmer Jerry P.1, Utzschneider Kristina M.1, Gebremedhin Tsige1, Kernan-Schloss Abigail1, Kozedub Alexandra1, Montgomery Brenda K.1, Morse Emily J.1, Xiang Anny H.1, Trigo Enrique1, Beale Elizabeth1, Hendee Fadi N.1, Katkhouda Namir1, Nayak Krishan1, Martinez Mayra1, Montgomery Cortney1, Wang Xinhui1, Lachin John M.1, Hogan Ashley N.1, Marcovina Santica1, Harting Jessica1, Albers John1, Hill Dave1, Savage Peter J.1
Affiliation:
1. RISE Coordinating Center, Rockville, MD
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.
Funder
National Institute of Diabetes and Digestive and Kidney Diseases National Center for Advancing Translational Sciences
Publisher
American Diabetes Association
Subject
Advanced and Specialized Nursing,Endocrinology, Diabetes and Metabolism,Internal Medicine
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