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

• Published in: Diabetes care Vol. 41; no. 8; pp. 1717 - 1725
• Main Authors: Nadeau, Kristen J., Hannon, Tamara S., Edelstein, Sharon L., Arslanian, Silva A., Caprio, Sonia, Leschek, Ellen W., Zeitler, Philip S., Buchanan, Thomas A., Ehrmann, David A., Mather, Kieren J., Kahn, Steven E., Gross, Susan, Williams, Jayne, Cree-Green, Melanie, Reyes, Yesenia Garcia, Vissat, Krista, Brown, Kathleen, Guerra, Nancy, Porter, Kristin, Savoye, Mary, Pierpont, Bridget, Garrett, Tammy, Lteif, Amale, Patel, Aniket, Chisholm, Robin, Moore, Karen, Pirics, Vivian, Pratt, Linda, Temple, Karla A., Rue, Abby, Barengolts, Elena, Mokhlesi, Babak, Van Cauter, Eve, Sam, Susan, Miller, M. Annette, Atkinson, Karen M., Palmer, Jerry P., Utzschneider, Kristina M., Gebremedhin, Tsige, Kernan-Schloss, Abigail, Kozedub, Alexandra, Montgomery, Brenda K., Morse, Emily J., Xiang, Anny H., Trigo, Enrique, Beale, Elizabeth, Hendee, Fadi N., Katkhouda, Namir, Nayak, Krishan, Martinez, Mayra, Montgomery, Cortney, Wang, Xinhui, Lachin, John M., Hogan, Ashley N., Marcovina, Santica, Harting, Jessica, Albers, John, Hill, Dave, Savage, Peter J.
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.08.2018
• Subjects: 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; Pathophysiology/Complications; Young Adult
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/dc18-0787

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. 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). No significant differences were observed between treatment groups at baseline, 12 months, or 15 months in β-cell function, BMI percentile, HbA , 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. HbA 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. 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.