Preventing Weight Regain After Glucagon-Like Peptide‑1 Therapy Discontinuation: A Pilot Randomized Controlled Trial

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are effective treatments for obesity, but discontinuation is common due to cost, insurance coverage limitations, side effects, patient preference, and other factors. Weight regain often occurs rapidly after cessation, yet few evidence-based strategies exist to support weight maintenance during this transition. This pilot randomized trial examined whether a digital wellness application or medically tailored meals (MTM) could mitigate weight gain during the first 4 months after GLP-1 cessation.

In this pilot randomized trial, adults with prior GLP-1-induced weight loss were randomized to usual care, wellness application, or MTM at the time of GLP-1 cessation. Surveys assessed adherence and satisfaction (primary outcome) as well as exploratory outcomes, diet quality, and perceived health. Weight (exploratory) was measured monthly using validated Bluetooth scales.

Participants (n = 39) were randomized to control (N = 14), digital wellness application (N = 12), or MTM (N = 13) and had a mean baseline BMI 31.4 (SD 6.3) kg/m². Diet quality, perceived health, adherence, and satisfaction did not significantly differ by group, though some estimates suggested possible trends favoring the wellness application. Relative to control, both the wellness application and MTM groups had less total weight gain: Wellness application -7.16% (95% CI: -12.27, -2.04) and MTM -7.17% (-12.20, -2.14).

These findings suggest that structured support may attenuate early weight gain after GLP-1 cessation. Larger, more diverse trials with longer follow-up and clinical outcomes are needed to confirm results and clarify mechanisms.