A pilot sequential multiple assignment randomized trial for developing a biobehavioral adaptive intervention to improve insulin sensitivity in patients with stage 1 obesity

Abstract

Background: Intervention packages targeting obesity-related conditions often include multiple behavioral and pharmacological components, yet the independent and synergistic effects of these strategies on disease progression remain largely unexplored. Adaptive interventions offer a structured approach to tailoring treatments based on individual responses, but feasibility data in primary care settings are limited. The objective of this pilot Sequential Multiple Assignment Randomized Trial (SMART) was to investigate the feasibility of a 25-week adaptive biobehavioral intervention designed to improve insulin sensitivity among patients with stage 1 obesity. Methods: Forty participants were initially randomized to either nutrition counseling (NC) or exercise counseling (EC), both employing a weight-neutral approach. At week 8, insulin sensitivity was reassessed using the Quantitative Insulin Sensitivity Check Index (QUICKI). Participants with a > 5% improvement were classified as responders, while non-responders were re-randomized to either augment their first-stage intervention with metformin or switch to weight loss counseling (WLC). Feasibility outcomes included recruitment and retention, adherence to intervention components, and preliminary treatment effect estimates. Results: Findings support the overall feasibility of the SMART design, with high adherence to virtual counseling sessions and favorable participant retention. The study effectively differentiated responders from non-responders at week 8, with responders showing greater improvements in insulin sensitivity. Among non-responders, WLC and metformin provided a potential rescue effect, but overall insulin sensitivity remained lower than at of responders. While NC and WLC were preferred over EC and metformin, adherence to counseling sessions remained high across all interventions, regardless of preference. Metformin adherence posed challenges due to frequent gastrointestinal side effects and difficulties tracking usage. Conclusions: This pilot study supports the feasibility of an adaptive biobehavioral intervention for improving insulin sensitivity among adults with obesity in a primary care setting. However, further refinement is needed to enhance clinical integration, optimize intervention messaging, and improve medication tracking. Findings from this study will inform a second pilot SMART, laying the foundation for a full-scale primary-care embedded intervention delivering personalized, adaptive strategies for improving cardiometabolic health. Trial registration: NCT04392283 on April 19th, 2020.