Adaptive dietary and exercise strategies for weight loss in Adults with Prediabetes Trial (ADAPT): a sequential...

Dietary carbohydrate restriction, time-restricted eating (TRE), and exercise are common strategies for weight loss and improving glycemic control. However, the optimal combination and sequence of these strategies is unclear.

We investigated adaptive treatment strategies for weight loss and improving cardiometabolic health in adults with overweight or obesity (BMI [in kg/m²] ≥27) and prediabetes.

ADAPT was a 16-wk group-based weight loss Sequential Multiple Assignment Randomized Trial. In total, 83 adults were initially randomized to either a calorie-restricted reduced carbohydrate (RC) diet or high-carbohydrate (HC) diet. Nonresponders (<2.5% weight loss at week 4) were rerandomly assigned to augment initial dietary prescriptions with either TRE or exercise counseling.

Of 82 participants (53.8 ± 11.7 y; 84.3% females; BMI: 38.3 ± 7.2) who completed week 4 assessments, 46 (55.4%) were nonresponders and rerandomly assigned to TRE (n = 22) or exercise (n = 24). Weight loss at week 16 was similar between HC and RC (0.15 kg; 95% CI: -1.86, 2.16 kg; P = 0.88). Although the HC group showed greater improvements in fasting glucose, (-8.0 mg/dL; 95% CI: -15.29, -0.67 mg/dL), changes in A1c, fasting insulin, and quantitative insulin sensitivity check index were not different between HC and RC. Among nonresponders, assignment to second-stage interventions of TRE or exercise did not differentially affect changes in any study outcomes, and less weight loss was achieved among early nonresponders compared with responders despite the addition of TRE or exercise.

The group-based program resulted in clinically significant weight loss that was similar between calorie-restricted HC and RC diets. However, counseling to follow a HC diet reduced fasting glucose compared with RC. Patients with obesity and prediabetes who are unable to achieve early weight loss may require more intensive and costly intervention strategies (i.e., meal provisions and supervised exercise) to improve obesity treatment outcomes. This trial was registered at ClinicalTrials.gov as NCT04745572 (https://clinicaltrials.gov/study/NCT04745572?term=NCT04745572&rank=1).