Despite the increasing use of pharmacological and bariatric surgery to treat obesity, weight-loss lifestyle intervention remains the first-line treatment. Digital health is coming to meet individual needs and makes obesity treatment more accessible, so this work aims to evaluate the safety and performance of a Digital Therapy for Obesity App (DTxO) in improving weight loss and weight-loss maintenance in obese patients exposed to an experimental nonpharmacological treatment program. Here we present the study protocol of a prospective, multicenter, pragmatic, randomized, double-arm, placebo-controlled, parallel, single-blind study on obese patients who will be treated with a new digital therapy to obtain an improvement in their disease condition through the application of different simultaneous strategies (a dietary plan and customized advice program, a customized physical exercise program plan, a cognitive–behavioural assessment and program, alerts and reminders, dedicated section on prescribed drugs intake, and chat and online visits with clinical professionals). We believe that DTxO will offer a promising intervention channel and self-regulation tool holding the potential to reduce treatment burden and reach more people by replacing some in-person contact with phone or digital communication, improving self-engagement and reducing the high demands the “obesity pandemic” for both patients and national health services in terms of time, cost, and effort.
Background: Obesity is a chronic, relapsing disease influenced by environmental, lifestyle, biological, and genetic factors, affecting over 1 billion people globally. Treatment for adults typically involves multicomponent lifestyle interventions—diet, physical activity, and behavior change—for at least 6-12 months. However, adherence is often low, and in-person sessions can be time-consuming and costly. Digital therapeutics (DTx), which enhance patient engagement and support long-term outcomes, have proven effective in managing chronic and mental health conditions. DTx offer scalable, evidence-based solutions with the potential to improve obesity management. Objective: The Digital Therapy to Promote Weight Loss in Patients With Obesity by Increasing Their Adherence to Treatment (DEMETRA) study is a prospective, multicenter, pragmatic, randomized, double-arm, single-blind, placebo-controlled trial evaluating the 6-month efficacy of an innovative, multicomponent digital intervention for obesity, which combines dietary, physical activity, and behavioral strategies in people with obesity (primary objective). Secondary objectives were assessing changes in BMI, waist circumference, blood pressure, glucose metabolism, lipid profile, adherence, and factors associated with absolute 6-month weight loss. Methods: The trial was conducted at 2 obesity centers in Italy with 246 participants aged 18-65 years (BMI 30-45 kg/m2), randomly assigned to either the Digital Therapeutics for Obesity (DTxO) app or a placebo app. DTxO offered personalized diet plans, exercise routines, and psycho-behavioral support, while the placebo app only allowed users to log data without feedback. Both groups followed a Mediterranean-style low-calorie diet with an 800 kcal/day deficit. On average, participants used the DTxO app for 42 minutes/day and the placebo app for 35 minutes, primarily for physical activity tracking. Univariable and multivariable generalized linear models were used to assess associations with 6-month absolute weight change (primary end point) and percent weight change (secondary end point). Results: Overall, 207 participants (84.1%) completed the 6-month visit. Both arms achieved a statistically significant absolute (DtxO: –3.2 kg, IQR –6.0 kg to –0.9 kg; placebo: –4.0 kg, IQR –6.9 kg to –0.5 kg; P<.001) and percent loss in body weight (DtxO: –3.0%, IQR –5.7% to –0.8%; placebo: –4.0%, IQR –8.5% to –0.5%; P<.001) after 6 months, without significant between-group differences (univariable generalized linear models: P=.34 and P=.17, respectively). Univariable regression analyses showed a significant association between adherence to app use and 6-month absolute weight loss (β=–.06, SE 0.02, P=.01) as well as percent weight loss (β=–.05, SE 0.01, P=.01). Adherent participants, defined as those with overall adherence at or above the 75th percentile of daily usage, included 35 individuals in the intervention group and 10 in the placebo group. In this subgroup, the estimated 6-month mean absolute weight change was –7.02 kg (95% CI –9.45 to –4.59) in the DTxO-adherent group and –3.50 kg (95% CI –7.01 to 0.01) in the placebo-adherent group (P=.02). The estimated 6-month mean percent change in weight was –6.31% (95% CI –8.86 to –3.76) in the DTxO-adherent group and –2.78% (95% CI –6.48 to 0.92) in the placebo-adherent group (P=.03). A significantly greater weight loss (P=.01 for study arm, either on absolute or percent change in weight from baseline) among adherent participants randomized to the DTxO app was also confirmed by analyses using mixed linear models for repeated measures. Conclusions: Although overall weight loss did not differ significantly between the DTxO and placebo groups, participants who used the DTxO app for at least 40% of the expected time achieved significantly greater weight loss. These results suggest that higher engagement with DTx can improve obesity outcomes. Further research should explore combining DTxO with pharmacological treatments or bariatric surgery. Trial Registration: ClinicalTrials.gov NCT05394779; https://clinicaltrials.gov/ct2/show/NCT05394779