Weight change in the management of youth-onset type 2 diabetes: the TODAY clinical trial experience

Abstract

Background: The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial documented that metformin plus rosiglitazone, but not metformin plus lifestyle intervention, provided superior durability of glycemic control relative to metformin monotherapy.

Objectives: We examined weight changes among TODAY participants that completed at least 6 months of treatment, evaluated predictors of lifestyle outcome, and examined whether weight changes were related to cardiometabolic outcomes across treatment arms.

Methods: The 595 youth with type 2 diabetes, (85.1% of randomized participants aged 11-17 years) completed assessments of weight-related and cardiometabolic measures at months 0, 6, 12 and 24. Repeated measures models were used to investigate associations over time.

Results: Lifestyle intervention did not enhance outcome relative to metformin alone and no predictors of response to lifestyle treatment were identified. However, changes in percent overweight across treatment arms were associated with changes in multiple cardiometabolic risk factors, and decreases of ≥ 7% in overweight were associated with significant benefits over 24 months.

Conclusions: Although adjunctive intensive lifestyle intervention did not improve weight-related outcomes, weight changes in the full TODAY sample were associated with small, but significant improvements in cardiometabolic status, highlighting the importance of optimizing weight management in youth with T2DM.

Trial registration: ClinicalTrials.gov NCT00081328.

Keywords: behavioral weight control; cardiometabolic risk; lifestyle; type 2 diabetes.

Conflict of interest statement

Conflicts of interest

The TODAY Study Group thanks the following companies for donations in support of the study’s efforts: Becton, Dickinson and Company, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, LifeScan, Inc., Pfizer, and Sanofi-Aventis. MDM is a member of the Scientific Advisory Board of Weight Watchers International, Inc. DEW is a consultant for Shire Pharmaceuticals. PZ is a consultant for Daiichi-Sankyo, Astra-Zeneca, Merck, Takeda, and Eli Lilly. NWA is a consultant for Daiichi-Sankyo. LE, BL, KH, CEIL and DJB have nothing to disclose.

© 2016 World Obesity Federation.

Figures

Figure 1

Multi-panel figure of change from baseline (mean and SE bars) in cardiometabolic outcome (hemoglobin A1c [HbA1c] (A); systolic blood pressure [SBP] (B); diastolic blood pressure [DBP] (C); low-density lipoprotein LDL cholesterol (D); high-density lipoprotein (HDL) cholesterol (E); total cholesterol (F); triglycerides (G); and c-peptide oral disposition index [oDI] (H) at month 6, 12 and 24, separately for youth who achieved a drop of ≥7% in percent overweight since baseline vs. those who did not. The ‘*’ indicates a significant difference (P < .001) between the two groups at a particular time point, based on GEE repeated-measures models adjusted for the baseline value of the cardiometabolic outcome, visit, treatment, sex, race-ethnicity, age at baseline and change in percent overweight during run-in. C-peptide oDI based on OGTT data not available at month 12 per study protocol.