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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

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Weight Loss to Improve Obesity-Related Complications

I think it is very important to understand and discuss realistic weight loss goals with patients, but the conversation should also include benchmarks that are associated with disease change.

For example, to slow or stop progression from metabolic syndrome or prediabetes to T2D, a weight loss of approximately 7% might be sufficient, although 10% weight loss will be more likely to prevent T2D. When managing patients with established cardiometabolic disease, 5% to 15% weight loss is associated with improved health outcomes, and patients with MASH need to lose ≥10% of their body weight to make a major difference. For other conditions, such as OSA and osteoarthritis, weight loss of 10% has demonstrated benefits.34 In general, helping patients lose at least 10% weight loss can slow progression of disease, and some can be reversed with 15% weight loss.

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Weight Loss Is Sustained Over Years With Semaglutide or Tirzepatide

There is very good evidence that patients can achieve sustained weight loss of least 10% of their body weight with semaglutide and tirzepatide. In the SELECT trial, patients receiving semaglutide achieved sustained weight loss of approximately 10% to approximately 4 years. In the SURMOUNT trial, the majority of patients (69%) receiving tirzepatide 15 mg achieved and sustained nearly 30% weight loss at approximately 3 years. These data show us that AOMs can help patients achieve and maintain disease-modifying weight loss (ie, ≥10%) for at least 3-4 years.35,36 

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SURMOUNT-5 Post Hoc Analysis: Tirzepatide vs Semaglutide in Patients With Obesity and Without T2D

There has been one head-to-head trial (SURMOUNT-5) that looked at tirzepatide vs semaglutide in patients with obesity and without T2D. Looking at the results, there was a benefit of -20.2% weight loss with tirzepatide vs -13.7% weight loss with semaglutide at 72 weeks. Both of these agents are excellent treatment options, but patients may be able to achieve greater weight loss with tirzepatide.37,38 I suspect that we will continue to see more agents introduced that help patients achieve this threshold of weight loss and success with health improvement.

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SURMOUNT-5: Adverse Events

With any AOM, the benefit of significant weight loss needs to be balanced against the potential for AEs. Gastrointestinal AEs are common with all incretin-based therapies, but it is important to note that discontinuation of these agents because of AEs is uncommon. HCPs will see patients experience nausea, decreased appetite, and occasional vomiting or diarrhea and should counsel patients on ways to minimize or mitigate these effects and on their tendency to go away over time. If patients are losing a lot of weight, they might have an increased risk for cholelithiasis, which is also something to counsel patients about, and dose reduction may be appropriate.

In comparing the safety profiles of tirzepatide and semaglutide in the head-to-head SURMONUT-5 trial, a higher rate of injection reactions has been observed with tirzepatide and a slightly higher rate of treatment discontinuations because of gastrointestinal AEs has been observed with semaglutide.37

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Real-world Weight Loss With Semaglutide and Tirzepatide in Overweight/Obesity Without T2D

Considering real-world data again, a retrospective, noninterventional study used the Komodo Health dataset to assess patients with pharmacy claims for tirzepatide or semaglutide. Among those receiving semaglutide, approximately 84% reached the maximum 2.4 mg dose vs 26% in the tirzepatide cohort who reached the maximum 15 mg dose after 1 year of treatment. Of note, approximately 65% of patients in the tirzepatide cohort reached doses ≥10 mg, which are associated with significant weight loss.

Among those who reached the maximum dose of semaglutide, patients achieved a mean weight loss of -14.6 kg (14.1%). In the tirzepatide cohort, the mean weight loss was -17.2 kg (16.5%). Based on expert experience, 15-kg weight loss seems to be critical for disease-modifying benefits. In both cohorts, >80% of patients achieved ≥5% weight loss, so all patients experienced a dramatic benefit with semaglutide or tirzepatide treatment.39

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Real-world Weight Loss With Semaglutide and Tirzepatide in Overweight/Obesity Without T2D

Another real-world study used the Truveta electronic health record database to assess the level of weight loss with tirzepatide and semaglutide treatment. The mean weight change with tirzepatide was -11.15% with tirzepatide vs -8.83% with semaglutide. More than 86% and 75% of patients lost ≥5% of their total body weight with tirzepatide and semaglutide, respectively. Furthermore, 60% and 38% of patients lost ≥10% of their total body weight with tirzepatide and semaglutide, respectively.40 These data show that there will be some “superresponders” and that the majority of patients will see disease-benefiting weight loss.

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STEP UP: Semaglutide 7.2 mg in Obesity

As we look to the future, use of a higher dose of semaglutide has been investigated for obesity management. The STEP UP trial evaluated 7.2 mg vs the recommended 2.4-mg dose, finding that patients achieved almost 19% weight loss and 48% of patients achieved ≥20% weight loss with semaglutide 7.2 mg.41 It is very likely that more dosing strategies and agents will be investigated and eventually expand our armamentarium for the treatment of obesity.

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Case 3: Your patient was started on an incretin-based obesity management medication that was prescribed based on the presence of sleep apnea. After 4 months, she is at her maximum tolerable dose, which is lower than the maximum allowable dose, and is still having bothersome gastrointestinal AEs. She has lost 7% of her initial weight but has not reached her goal of 10% weight loss. What would you recommend? 

Case 3: Key Points on Adjusting Therapy—Incretin-Based AOMs

When considering the different AOMs, it is important to understand that everybody will respond to a specific medication differently. If patients are not tolerating one incretin-based therapy well and approaches to improving tolerability are not effective, it is worthwhile to switch to another incretin-based agent both from a safety profile perspective as well as a potential therapeutic benefit perspective, knowing that there will be variation from one person to the next. Sometimes it is a financial decision. It is worthwhile to check in with patients to ensure they are injecting the AOM correctly and staying on schedule because it can be complicated to take multiple medications at a time. HCPs should also check in with patients to address any challenges with treatment and access.

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