ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2019) 16 12.4 | DOI: 10.1530/ey.16.12.4

Type 2 Diabetes

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

Bai RISE Consortium


Diabetes Care 2018;41:1717–1725.
DOI: 10.2337/dc18-0787

Summary: In a randomized, open label clinical trial of 91 adolescents with IGT or new onset T2DM, one-year early interventions with long-acting insulin followed by metformin, or with metformin alone failed to prevent deterioration in beta-cell function.

Comment: Among adults with IGT or recent-onset T2DM, treatment with metformin has previously been reported to improve β-cells function and reduced diabetes progression by 31% over 3 years; and 2 weeks of intensive insulin therapy improved and maintained beta-cell function, resulting in prolonged remission from requiring diabetes medication.

T2DM in adolescents appears to be more aggressive than in adults, therefore interventions to preserve or improve beta-cell function in youth are highly important. The Restoring Insulin Secretion (RISE) Pediatric Medication Study assessed whether initial short-term treatment with insulin glargine for 3 months followed by metformin for 9 months would preserve or improve beta-cell function compared with metformin alone, with a sustained effect after withdrawal of therapy.

No significant differences were observed between treatment groups at baseline, 12 months or 15 months in beta-cell function, BMI percentile, HbA1c, fasting glucose, or oral glucose tolerance test 2-h results. In both treatment groups, clamp-measured beta-cell function was significantly lower at 12 and 15 months versus baseline. BMI was higher in the glargine followed by metformin versus metformin alone group between 3 and 9 months. These findings may indicate a more aggressive disease course for T2DM in younger patients, and highlight the need for alternate approaches to preserve beta-cell function in youth.

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