PI-086 - COMPARISON OF DISEASE CHARACTERISTICS IN ADULTS AND CHILDREN WITH TYPE 2 DIABETES MELLITUS: IMPLICATION FOR ANTIDIABETIC DRUG DEVELOPMENT IN CHILDREN.

T. Liu, J. Penzenstadler, J. Earp, J. Vaidyanathan; US Food and Drug Administration, Silver Spring, MD, USA.

Background: In addition to insulin injection, currently, only three drugs (exenatide, liraglutide, and metformin) have been approved in children with type 2 diabetes mellitus (T2DM) by FDA. Majority of the clinical studies in children with T2DM failed to meet their primary efficacy endpoint.

Methods: We reviewed all the pediatric T2DM clinical trials submitted to US FDA from 2000 to 2021 and the TODAY trial conducted by NIH. Demographics and disease characteristics (fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), Homeostatic model assessment (HOMA)-Insulin Resistance (IR), and HOMA-β-cell function(Beta)) were compared with adults with T2DM and healthy subjects.

Results: 1470 children with T2DM from 10 clinical studies were included. On average, children and adults (N=857) with T2DM had a FPG of 158.8±60.1 mg/dL and 200±57.6 mg/dL, HbA1c of 8.0%±1.4% and 8.9%±1.3%, HOMA-Beta of 266.3%±426.0% and 40.2%±42.0%, HOMA-IR of 16.5±19.6 and 6.2±5.0, and BMI of 32.4±9.0 and 29.1±5.0 at baseline (mean±SD), respectively.

Conclusion: In children, the elevated HOMA-IR is likely responsible for the elevated FPG and HbA1c. However, adults with T2DM showed both decreased HOMA-beta and increased HOMA-IR. Particularly, HOMA-IR is much higher in children with T2DM than adults. Therefore, children with T2DM could respond to treatment differently than adults.

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Figure 1 Distribution of Homeostatic model assessment (HOMA) β-cell function (Beta) and insulin resistance (IR) in children with T2DM, adults with T2DM, and healthy subjects