weight loss

Background
Oral semaglutide at a dose of 25 mg may provide an alternative treatment option to injectable semaglutide (2.4 mg) and higher-dose oral semaglutide (50 mg) for persons with overweight or obesity.

Methods
In a 71-week, double-blind, randomized, placebo-controlled trial conducted at 22 sites in four countries, we enrolled persons without diabetes who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30 or higher or a BMI of 27 or higher with at least one obesity-related complication. The participants were randomly assigned in a 2:1 ratio to receive oral semaglutide (25 mg) or placebo once daily, plus lifestyle interventions. The coprimary end points at week 64 were the percent change in body weight and a reduction of 5% or more in body weight; confirmatory secondary end points included reductions in body weight of 10% or more, 15% or more, and 20% or more and the change in the Impact of Weight on Quality of Life–Lite Clinical Trials Version (IWQOL-Lite-CT) Physical Function score.

Results
A total of 205 participants were randomly assigned to receive oral semaglutide, and 102 to receive placebo. The estimated mean change in body weight from baseline to week 64 was −13.6% in the oral semaglutide group and −2.2% in the placebo group (estimated difference, −11.4 percentage points; 95% confidence interval, −13.9 to −9.0; P<0.001). Participants in the oral semaglutide group were significantly more likely than those in the placebo group to have body-weight reductions of 5% or more, 10% or more, 15% or more, and 20% or more (P<0.001 for all comparisons) and to have an improved IWQOL-Lite-CT Physical Function score (P<0.001). Gastrointestinal adverse events were more common with oral semaglutide than with placebo (74.0% vs. 42.2%).

Conclusions
Oral semaglutide at a dose of 25 mg once daily resulted in a greater mean reduction in body weight than placebo in participants with overweight or obesity. (Funded by Novo Nordisk; OASIS 4 ClinicalTrials.gov number, NCT05564117.)

Importance: Approximately 19.7% of children and adolescents aged 2 to 19 years in the US have a body mass index (BMI) at or above the 95th percentile for age and sex, based on Centers for Disease Control and Prevention growth charts from 2000. The prevalence of high BMI increases with age and is higher among Hispanic/Latino, Native American/Alaska Native, and non-Hispanic Black children and adolescents and children from lower-income families.

Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the evidence on interventions (behavioral counseling and pharmacotherapy) for weight loss or weight management in children and adolescents that can be provided in or referred from a primary care setting.

Population: Children and adolescents 6 years or older.

Evidence assessment: The USPSTF concludes with moderate certainty that providing or referring children and adolescents 6 years or older with a high BMI to comprehensive, intensive behavioral interventions has a moderate net benefit.

Recommendation: The USPSTF recommends that clinicians provide or refer children and adolescents 6 years or older with a high BMI (≥95th percentile for age and sex) to comprehensive, intensive behavioral interventions. (B recommendation).

Importance: Obesity is a disease with a large socioeconomic burden. Endoscopic sleeve gastroplasty (ESG) is a minimally invasive endoscopic bariatric procedure with wide global adoption. More recently, new weight-loss medications, such as glucagon-like peptide-1 receptor agonists (eg, semaglutide), have attracted increased attention due to their efficacy. However, their cost-effectiveness over an extended period compared with ESG is a critical gap that needs to be better explored for informed health care decision-making.

Objective: To assess the cost-effectiveness of semaglutide compared with ESG over 5 years for individuals with class II obesity.

Design, setting, and participants: This economic evaluation study, conducted from September 1, 2022, to May 31, 2023, used a Markov cohort model to compare ESG and semaglutide, with a no-treatment baseline strategy. The study comprised adult patients in the US health care system with class II obesity (body mass index [BMI] of 35-39.9). The base case was a 45-year-old patient with class II obesity (BMI of 37). Patients undergoing ESG were subjected to risks of perioperative mortality and adverse events with resultant costs and decrement in quality of life.

Interventions: Strategies included treatment with semaglutide and ESG.

Main outcomes and measures: Costs (2022 US dollars), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) with a willingness-to-pay threshold of $100 000/QALY. A 5-year time horizon with a cycle length of 1 month with a 3% discount rate was used. Probabilities, costs, and quality-of-life estimates of the model were derived from published literature. One-way, 2-way, and probabilistic sensitivity analyses were also performed.

Results: The model found that ESG was more cost-effective than semaglutide over a 5-year time horizon, with an ICER of -$595 532/QALY. Endoscopic sleeve gastroplasty added 0.06 QALYs and reduced total cost by $33 583 relative to semaglutide. The results remained robust on 1-way and probabilistic sensitivity analyses. Endoscopic sleeve gastroplasty sustained greater weight loss over 5 years vs semaglutide (BMI of 31.7 vs 33.0). To achieve nondominance, the annual price of semaglutide, currently $13 618, would need to be $3591.

Conclusions and relevance: This study suggests that ESG is cost saving compared with semaglutide in the treatment of class II obesity. On price threshold analyses, a 3-fold decrease in the price of semaglutide is needed to achieve nondominance.

Importance: More than 40% of US adults have obesity, which increases the risks for multiple chronic diseases and premature mortality. Historically, nonsurgical interventions often have not led to sufficient weight loss and maintenance to improve health, but highly effective antiobesity medications (AOMs) have recently become available, and additional effective therapeutics are under development. Given that most medical care for adults with obesity is delivered in primary care settings, guidance for integrating weight-management approaches is needed.

Observations: Lifestyle interventions can lead to a mean weight loss of 2% to 9% of initial weight at 1 year and increase the likelihood of weight loss of 5% or more, but weight regain over time is common even with continued treatment. Adjunctive treatments, including AOMs and surgical approaches, can lead to larger, more sustained weight loss and improvements in numerous obesity-associated medical conditions. Highly effective AOMs, including nutrient-stimulated hormone-based therapies, induce mean weight loss of 15% or more. Barriers to intervention, including access to care, have a disproportionate influence on populations most affected by obesity and its consequences.

Conclusions and relevance: Primary care clinicians play a vital role in the assessment, management, and support of patients with obesity. With careful clinical assessment and shared decision-making, a flexible treatment plan can be developed that reflects evidence of treatment efficacy, patient preference, and feasibility of implementation. Adjunctive therapies to lifestyle interventions, including more effective pharmacotherapeutics for obesity, offer hope to patients and the potential for considerable improvements in health and quality of life.