Impact of Insulin and Metformin Versus Metformin Alone on β-Cell Function in Youth With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes
RISE Consortium, Kristen J Nadeau, Tamara S Hannon, Sharon L Edelstein, Silva A Arslanian, Sonia Caprio, Ellen W Leschek, Philip S Zeitler, Thomas A Buchanan, David A Ehrmann, Kieren J Mather, Steven E Kahn, Susan Gross, Jayne Williams, Melanie Cree-Green, Yesenia Garcia Reyes, Krista Vissat, Kathleen Brown, Nancy Guerra, Kristin Porter, Mary Savoye, Bridget Pierpont, Tammy Garrett, Amale Lteif, Aniket Patel, Robin Chisholm, Karen Moore, Vivian Pirics, Linda Pratt, Karla A Temple, Abby Rue, Elena Barengolts, Babak Mokhlesi, Eve Van Cauter, Susan Sam, M Annette Miller, Karen M Atkinson, Jerry P Palmer, Kristina M Utzschneider, Tsige Gebremedhin, Abigail Kernan-Schloss, Alexandra Kozedub, Brenda K Montgomery, Emily J Morse, Anny H Xiang, Enrique Trigo, Elizabeth Beale, Fadi N Hendee, Namir Katkhouda, Krishan Nayak, Mayra Martinez, Cortney Montgomery, Xinhui Wang, John M Lachin, Ashley N Hogan, Santica Marcovina, Jessica Harting, John Albers, Dave Hill, Peter J Savage, RISE Consortium, Kristen J Nadeau, Tamara S Hannon, Sharon L Edelstein, Silva A Arslanian, Sonia Caprio, Ellen W Leschek, Philip S Zeitler, Thomas A Buchanan, David A Ehrmann, Kieren J Mather, Steven E Kahn, Susan Gross, Jayne Williams, Melanie Cree-Green, Yesenia Garcia Reyes, Krista Vissat, Kathleen Brown, Nancy Guerra, Kristin Porter, Mary Savoye, Bridget Pierpont, Tammy Garrett, Amale Lteif, Aniket Patel, Robin Chisholm, Karen Moore, Vivian Pirics, Linda Pratt, Karla A Temple, Abby Rue, Elena Barengolts, Babak Mokhlesi, Eve Van Cauter, Susan Sam, M Annette Miller, Karen M Atkinson, Jerry P Palmer, Kristina M Utzschneider, Tsige Gebremedhin, Abigail Kernan-Schloss, Alexandra Kozedub, Brenda K Montgomery, Emily J Morse, Anny H Xiang, Enrique Trigo, Elizabeth Beale, Fadi N Hendee, Namir Katkhouda, Krishan Nayak, Mayra Martinez, Cortney Montgomery, Xinhui Wang, John M Lachin, Ashley N Hogan, Santica Marcovina, Jessica Harting, John Albers, Dave Hill, Peter J Savage
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.
Trial registration: ClinicalTrials.gov NCT01779375.
© 2018 by the American Diabetes Association.
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Source: PubMed