Impact of insulin and metformin versus metformin alone on β-cell function in youth with impaired glucose tolerance or recently diagnosed type 2 diabetes

Kristen J. Nadeau, Tamara Hannon, Sharon L. Edelstein, Silva A. Arslanian, Sonia Caprio, Ellen W. Leschek, Philip S. Zeitler, Thomas A. Buchanan, David A. Ehrmann, Kieren Mather, Steven E. Kahn

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

OBJECTIVE: Pediatric type 2 diabetes prevalence is increasing, with β-cell dysfunction key in its pathogenesis. The RISE Pediatric Medication Study compared two approachesd glargine followed by metformin and metformin alonedin 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.

Original languageEnglish (US)
Pages (from-to)1717-1725
Number of pages9
JournalDiabetes Care
Volume41
Issue number8
DOIs
StatePublished - Aug 1 2018
Externally publishedYes

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Glucose Intolerance
Metformin
Type 2 Diabetes Mellitus
Insulin
Glucose
Therapeutics
Pediatrics
Glucose Tolerance Test
Insulin Resistance
Fasting
Research Design
Insulin Glargine

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Cite this

Impact of insulin and metformin versus metformin alone on β-cell function in youth with impaired glucose tolerance or recently diagnosed type 2 diabetes. / Nadeau, Kristen J.; Hannon, Tamara; Edelstein, Sharon L.; Arslanian, Silva A.; Caprio, Sonia; Leschek, Ellen W.; Zeitler, Philip S.; Buchanan, Thomas A.; Ehrmann, David A.; Mather, Kieren; Kahn, Steven E.

In: Diabetes Care, Vol. 41, No. 8, 01.08.2018, p. 1717-1725.

Research output: Contribution to journalArticle

Nadeau, KJ, Hannon, T, Edelstein, SL, Arslanian, SA, Caprio, S, Leschek, EW, Zeitler, PS, Buchanan, TA, Ehrmann, DA, Mather, K & Kahn, SE 2018, '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, vol. 41, no. 8, pp. 1717-1725. https://doi.org/10.2337/dc18-0787
Nadeau, Kristen J. ; Hannon, Tamara ; Edelstein, Sharon L. ; Arslanian, Silva A. ; Caprio, Sonia ; Leschek, Ellen W. ; Zeitler, Philip S. ; Buchanan, Thomas A. ; Ehrmann, David A. ; Mather, Kieren ; Kahn, Steven E. / Impact of insulin and metformin versus metformin alone on β-cell function in youth with impaired glucose tolerance or recently diagnosed type 2 diabetes. In: Diabetes Care. 2018 ; Vol. 41, No. 8. pp. 1717-1725.
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abstract = "OBJECTIVE: Pediatric type 2 diabetes prevalence is increasing, with β-cell dysfunction key in its pathogenesis. The RISE Pediatric Medication Study compared two approachesd glargine followed by metformin and metformin alonedin 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.",
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AU - Hannon, Tamara

AU - Edelstein, Sharon L.

AU - Arslanian, Silva A.

AU - Caprio, Sonia

AU - Leschek, Ellen W.

AU - Zeitler, Philip S.

AU - Buchanan, Thomas A.

AU - Ehrmann, David A.

AU - Mather, Kieren

AU - Kahn, Steven E.

PY - 2018/8/1

Y1 - 2018/8/1

N2 - OBJECTIVE: Pediatric type 2 diabetes prevalence is increasing, with β-cell dysfunction key in its pathogenesis. The RISE Pediatric Medication Study compared two approachesd glargine followed by metformin and metformin alonedin 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.

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