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Latest evidence in obesity management

CE / CME

The Latest in Obesity Management: Current Evidence for Primary Care

Physician Assistants/Physician Associates: 1.00 AAPA Category 1 CME credit

ABIM MOC: maximum of 1.00 Medical Knowledge MOC point

Nurse Practitioners/Nurses: 1.00 Nursing contact hour

Physicians: maximum of 1.00 AMA PRA Category 1 Credit™

Released: September 25, 2025

Expiration: September 24, 2026

Jay H. Shubrook
Jay H. Shubrook, DO, FACOFP, FAAFP
CME/CE Information

Activity

Progress
1 2 3
Course Completed

REDEFINE 1: Coadministered Cagrilintide and Semaglutide in Adults With Overweight/Obesity, No T2D

Many new agents for obesity management are in development. This section highlights some with recently presented data, but these are not the only agents in the pipeline.

In the REDEFINE 1 trial, cagrilintide and semaglutide were coadministered and compared with cagrilintide alone, semaglutide alone, and placebo in adults with overweight or obesity. This was a multicenter, randomized phase III trial that enrolled adults with BMI ≥30 kg/m2 or adults with BMI ≥27 mg/k2 and ≥1 weight-related complication. Of note, both cagrilintide and semaglutide independently are beneficial, and they may have a synergistic effect when used together.

In looking at weight loss achieved, patients treated with the combination of cagrilintide and semaglutide lost a mean -20% vs -15% with semaglutide alone, -12% with cagrilintide alone, and -3% with placebo. Thinking about weight loss milestones, the overwhelming majority of patients (92%) achieved ≥5% weight loss and more than one half (54%) achieved ≥20% weight loss with the combination of cagrilintide and semaglutide. This looks like another potent agent that could improve obesity-related health problems.42

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REDEFINE 1: Safety

The combination of cagrilintide and semaglutide has an AE profile that is similar to the individual therapies. Most AEs were gastrointestinal. A higher proportion of patients treated with the cagrilintide/semaglutide combination discontinued treatment because of AEs (6%) compared with the individual agents (3% to 4%), but the gastrointestinal and injection-site reactions appear to be the biggest concerns.42

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Amycretin: Unimolecular Dual GLP-1 and Amylin Receptor Agonist

Another novel agent in the pipeline is amycretin, a unimolecular dual GLP-1/amylin receptor agonist. Amylin-based therapy was developed to potentiate insulin secretion, but research is now finding ways to use it in novel therapeutic approaches.

A single-center, double-blind, randomized phase Ib/IIa trial enrolled adults with BMI 27.0-39.9 kg/m2 and A1C <6.5% and treated them with once-weekly, subcutaneous amycretin vs placebo. At 36 weeks, the estimated treatment difference in weight loss was more than -20% with amycretin vs placebo. So this is a another potent AOM, particularly when compared with placebo. Finally, the safety profile of amycretin was similar to what we have seen in this drug class.43

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SCALE Kids: Liraglutide for Children 6 to <12 Years of Age With Obesity

More than 20 years of data and experience with incretin-based therapies has shown that they are efficacious, and they benefit multiple systems. Given the wealth of evidence and increasing rates of obesity in children and young adults, it is likely that there will be more studies investigating use of incretin-based therapies in adolescents and children who have excessive adiposity. In addition to looking at weight loss when used alone, the studies may also examine cardiometabolic benefits and roles in augmenting bariatric surgery.44

 

Highlighting one study in younger children, the SCALE Kids trial looked at liraglutide in children aged 6 to less than 12 years with obesity. It is important to recognize that children with obesity at 6 years of age have a very high likelihood of having obesity for life.

 

This trial was 56 weeks long and had a 26-week follow-up extension. It compared liraglutide 3 mg (or the maximum tolerated dose) with placebo. The mean BMI was 31 kg/m2 and an alarming rate of 55% of patients had ≥1 obesity-related complication at screening. The BMI change was -6% for liraglutide vs 2% for placebo.45 Although there was a clear reduction in BMI, remember that patients at this age are growing. Therefore, much of the weight gain that would occur with continual growth is attenuated with the use of the GLP-1 agonist liraglutide in this study.

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Summary

Today is a new day in the world of managing obesity. There is enhanced guidance for diagnosing obesity that goes far beyond the use of BMI alone, including anthropomorphic and direct body fat measurements. Furthermore, this updated guidance should help HCPs identify preclinical and clinical obesity, and HCPs should offer all patients a comprehensive treatment plan to address obesity. This includes lifestyle modifications, pharmacotherapy, and surgical approaches. Every patient deserves to have an individualized treatment plan. Being prepared to use all the tools, including new therapies as they become available, will provide the best chance for patients with obesity to achieve their optimal health.

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