Objective: The aim of this study was to test the effectiveness of the OPTIFAST program (OP), a total meal replacement dietary intervention, compared with a food‐based (FB) dietary plan for weight loss.Methods: Participants with BMI 30 to 55 kg/m², age 18 to 70 years old, were randomized to OP or FB dietary and lifestyle interventions for 26 weeks, followed by a weight‐maintenance phase. Outcomes were percent change in body weight (%WL) from baseline to weeks 26 and 52, associated changes in body composition (using dual energy x‐ray absorptiometry), and adverse events. Primary analysis used repeated‐measures multivariable linear mixed models to compare outcomes between groups in a modified intention‐to‐treat fashion (mITT).Results: A total of 273 participants (83% of randomized; 135 OP, 138 FB) made up the mITT population. Mean age was 47.1 ± 11.2 years; 82% were female and 71% non‐Hispanic white. Baseline BMI was 38.8 ± 5.9 kg/m². At 26 weeks, OP %WL was 12.4% ± 0.6% versus 6.0% ± 0.6% in FB (P < 0.001). At 52 weeks, OP %WL was 10.5% ± 0.6% versus 5.5% ± 0.6% in FB (P < 0.001). Fat mass loss was greater for OP; lean mass loss was proportional to total weight loss. There was no difference in serious adverse event rates between groups.Conclusions: Compared with an FB approach, OP was more effective with greater sustained weight loss.

Recent publicity around the use of new antiobesity medications (AOMs) has focused the attention of patients and healthcare providers on the role of pharmacotherapy in the treatment of obesity. Newer drug treatments have shown greater efficacy and safety compared with older drug treatments, yet access to these drug treatments is limited by providers’ discomfort in prescribing, bias, and stigma around obesity, as well as by the lack of insurance coverage. Now more than ever, healthcare providers must be able to discuss the risks and benefits of the full range of antiobesity medications available to patients, and to incorporate both guideline based advice and emerging real world clinical evidence into daily clinical practice. The tremendous variability in response to antiobesity medications means that clinicians need to use a flexible approach that takes advantage of specific features of the antiobesity medication selected to provide the best option for individual patients. Future research is needed on how best to use available drug treatments in real world practice settings, the potential role of combination therapies, and the cost effectiveness of antiobesity medications. Several new drug treatments are being evaluated in ongoing clinical trials, suggesting that the future for pharmacotherapy of obesity is bright.