REDEFINE 5: CagriSema in East Asian Adults with Overweight or Obesity, With or Without T2D

Presenter: Yasushi Ishigaki

REDEFINE 5 was a phase 3a, double-blind, parallel group, multicenter trial involving adults with a BMI ≥27 kg/m² and ≥2 obesity-related complications (ORCs), or with a BMI ≥35 kg/m² and ≥1 ORC.

In this trial, once-weekly CagriSema 2.4 mg/2.4 mg significantly reduced body weight in East Asian adults with overweight or obesity, with or without type 2 diabetes, compared to semaglutide alone. 

Over 68 weeks, CagriSema led to an 18.4% weight reduction versus 11.9% with semaglutide, with more participants achieving greater achievement of bodyweight reductions of ≥5% (95.4% vs 78.7%; p<0.0001), ≥10% (81.9% vs 48.5%; p<0.0001), ≥15% (60.2% vs 30.0%; p<0.0001), ≥20% (39.4% vs 18.6%; p<0.0001), and ≥25% (22.4% vs 9.6%; p=0.002). CagriSema also improved waist circumference, HbA1c, lipids, CRP, and blood pressure. Visceral fat reduction was similar between groups. Gastrointestinal side effects were common but mostly mild. Overall, CagriSema demonstrated superior efficacy and comparable safety for weight management and cardiometabolic improvements in this population.

Semaglutide vs. Bariatric Surgery: Comparing Costs & Outcomes in Patients with Diabetes & Obesity

Presenter: Karan R. Chhabra

In a study of 8,071 adults with obesity and type 2 diabetes, bariatric surgery (n=4,768) was associated with lower out-of-pocket (OOP) costs ($3,796 vs $4,080; p=0.002) and higher insurance plan spending ($61,951 vs $55,960; p=0.001) compared to semaglutide (n=3,303). 

Surgery patients had fewer emergency visits (HR 0.77; p<0.001), inpatient admissions (HR 0.62; p<0.001), and major cardiovascular events (HR 0.43; p<0.001). At 3-year follow-up, semaglutide had higher OOP costs ($6,495 vs $5,317; p<0.001) and lower plan spending ($72,132 vs $77,076; p<0.001). Overall, surgery offered better clinical outcomes and lower personal financial burden.

Beyond BMI: The Impact of the New Lancet Commission Diagnostic Criteria on U.S. Obesity Prevalence

Presenter: Jennifer Hwang

Since obesity was recognized as a disease by the AMA in 2013, BMI has been the primary screening tool despite limitations. In 2025, the Lancet Commission introduced a new framework using waist measures (Waist circumference, Waist-Hip ratio and Waist-Height ratio), body fat percentage, and obesity-related dysfunction to classify obesity as preclinical or clinical. 

Using NHANES 2017–2018 data, this study compared prevalence under BMI and the new definition. Results show obesity prevalence rises from 42.7% to 79.3%, reclassifying millions across BMI categories. This broader definition may enhance identification of excess adiposity and dysfunction, impacting clinical care, public health planning, and policy for costly obesity treatments.

Effect of Semaglutide 2.4 mg in Chinese Adults with Overweight or Obesity (BMI ≥24 or ≥28): STEP 12

Presenter: Robert F Kushner

STEP 12 was a phase 3b trial evaluating semaglutide 2.4 mg for weight management in Chinese adults with overweight BMI ≥24-<28 kg/m² with ≥1 weight related comorbidities. or obesity BMI ≥28 - <30 kg/m² with or without comorbidities, 

Participants received semaglutide 2.4mg or placebo plus lifestyle intervention for 44 weeks. Semaglutide led to significantly greater weight loss (−12.1% vs −2.2%), waist circumference reduction (−9.0 cm vs −2.4 cm), and HbA1c improvement (−0.4% vs +0.1%). Over 80% achieved ≥5% weight loss. 

In Taiwanese participants, body composition improved. Adverse events were mostly gastrointestinal. Overall, semaglutide was effective and safe, aligning with global STEP findings in this East Asian population.

STEP UP: Efficacy of Semaglutide in Obesity Treatment Targets and Cardiovascular Risk Thresholds

Presenter: Carel W. Le Roux.

The STEPUP trial explored a treat-to-target (TTT) approach in obesity management using semaglutide (sema). 

Participants received sema 7.2 mg, 2.4 mg, or placebo for 72 weeks. More patients on sema 7.2 mg achieved BMI <27 kg/m² (26.7%) and WHtR <0.53 (25.5%) compared to other groups. Among those meeting these targets, a high proportion also met cardiovascular (CV) risk factor thresholds, including normoglycemia, healthy lipid levels, and blood pressure. Notably, 100% of patients who met both obesity targets also met ≥2 CV thresholds. 

These findings support TTT strategies and highlight sema 7.2 mg’s potential for improving obesity-related health outcomes.

Lower Real-World Risk of CV Events with Semaglutide 2.4 mg in People with Risk Factors for ASCVD

Presenter: Victoria Divino

In the SCORE-Primary Prevention Study, semaglutide 2.4 mg significantly reduced the risk of major adverse cardiovascular events (MACE) in 48,184 overweight/obese adults aged ≥45y with ≥3 atherosclerotic cardiovascular disease (CVD) risk factors but no prior CVD/diabetes. 

Semaglutide users had lower rates of 3-point MACE (HR 0.73; p<0.01), revised 3-point MACE (HR 0.59; p<0.001), 5-point MACE (HR 0.75; p<0.01), and revised 5-point MACE (HR 0.65; p<0.001) compared to non-users (n=96,368).Semaglutide use also significantly reduced HF hospitalization rates, all-cause mortality and CV-related mortality. The study used real-world data and robust statistical matching, showing semaglutide’s potential for primary prevention of cardiovascular events in high-risk populations outside of traditional clinical trial settings.

Weight Change After GLP-1 Discontinuation in US Patients Living with Overweight/Obesity or Diabetes

Presenter: Michael A. Weintraub

A retrospective study determined the weight change patterns in 17,935 patients with overweight/obesity ± T2DM, who discontinued glucagon-like peptide-1 (GLP-1) after ≥5% weight loss. 

Within one year of GLP-1 discontinuation, 58.4% patients regained weight. A greater weight regain was reported among those who initially lost more (56.1% patients in those with 5–<10% initial weight loss, 61.5% in 10–<15% weight loss, 62.3% in 15–<20% weight loss and 63.8% in ≥20% weight loss). Only 7.2% patients continued losing ≥10% post-discontinuation. Weight regain increased steadily over the year. These findings underscore the need for improved long-term obesity management strategies. 

Twenty-Four Month Efficacy of Anti-Obesity Medications in a Telemedicine Weight Management Clinic

Presenter: Kathleen Ruddiman

This retrospective observational study evaluated long-term real-world outcomes of anti-obesity medications (AOMs) in adults treated via a telemedicine weight management clinic between January 2022 and December 2024. 

Among 11,675 (≥18 years) patients on AOMs for ≥18 months, average weight loss was −18.53% (−19.19 kg); among 4,317 patients for ≥24 months, it was −20.27% (−21.29 kg) across all AOMs.  Long-acting AOMs (e.g., injectable semaglutide, dulaglutide, tirzepatide) showed superior efficacy: −18.75% at 18 months and −20.48% at 24 months. Oral AOMs (e.g., bupropion/naltrexone, metformin, oral semaglutide) yielded −12.95% and −15.35% respectively. No data were available for short-acting AOMs. Side effects declined over time. These findings support sustained weight loss with long-term AOM use in telemedicine settings.

Real-World Weight Loss Outcomes With Tirzepatide in Women Living With Polycystic Ovary Syndrome

Presenter: Ashley K. Clift

This retrospective cohort study evaluated tirzepatide’s effectiveness in 4,241 UK women with polycystic ovary syndrome (PCOS) and overweight/obesity using a digital weight loss (WL) service. Mean WL at 10 months was 18.81% (95% CI: 17.93–19.69%). 

Digitally engaged users achieved greater WL: 21.02% vs. 17.23% (absolute difference: 3.76%, p<0.001). Kaplan–Meier analysis showed 96.58% achieved ≥5%, 90.80% ≥10%, and 75.96% ≥15% WL. Engagement included lifestyle coaching, weekly weight tracking, and app use. These results highlight tirzepatide’s strong real-world efficacy in PCOS, with digital support significantly enhancing outcomes.

Improved Health-related Quality of Life with Tirzepatide vs Semaglutide: An Analysis of SURMOUNT-5

Presenter: Alpana Shukla

In the SURMOUNT-5 post hoc analysis, tirzepatide (TZP) showed greater improvements in health-related quality of life (HRQoL) compared to semaglutide (SEMA) in adults with obesity without type 2 diabetes. 

Both treatments improved physical component scores (PCS), while mental component scores (MCS) remained unchanged. TZP led to significantly better general health outcomes, especially in participants with limited physical function at baseline. Greater body weight (BW) reductions correlated with enhanced HRQoL, particularly in physical functioning, bodily pain, and general health. TZP had fewer participants with <10% BW loss, indicating stronger efficacy in improving HRQoL through weight reduction.

Clinical Obesity and Cancer Risk: A Longitudinal Analysis from the UK Biobank

Presenter: Yun Shen

In a UK Biobank study of 223,764 participants over a median 12.9 years, obesity-induced dysfunctions were strongly linked to cancer risk. Participants were categorized into 6 clusters based on baseline obesity and development of obesity induced dysfunctions.

During a mean follow-up of 12.9 years, A total of 27,814 cancer and 8,308 cancer related-deaths occurred. Cluster 2 (non-obese at baseline but developed dysfunctions) had the highest cancer incidence (HR=2.17; 95% CI: 2.09–2.26) and mortality (HR=2.27; 95% CI: 2.10–2.46). Cluster 4 (preclinical obesity without dysfunctions) had the lowest cancer risk (HR=0.89; 95% CI: 0.85–0.93). Pancreatic, breast, and GI cancers showed strongest associations. Findings emphasize the importance of identifying organ dysfunctions beyond BMI for cancer prevention and early intervention in obesity-related health risks.

Association Between Unhealthy Alcohol Use and GLP-1RA Receipt in Patients With and Without Obesity

Presenter: Alissa S. Chen

A cross-sectional study assessed the correlation between unhealthy alcohol use and glucagon-like peptide-1 receptor agonist use (GLP-1RA; exenatide, dulaglutide, liraglutide, semaglutide or tirzepatide) in over 2.1 million elderly type 2 diabetics with/without obesity.

GLP-1RA use was associated with reduced rates of unhealthy alcohol use (low AUDIT-C scores). This association was stronger among obese patients versus non-obese patients (prevalence ratio 0.78 vs. 0.81). The findings suggest that GLP-1RAs may influence alcohol-related behaviors, potentially due to shared neurobiological pathways involved in reward and craving. Study limitations include cross-sectional design, possible unadjusted confounding possibly affecting receipt of GLP-1RA and predominantly male cohort.

Association of Body Roundness Index With Coronary Artery Calcium Burden Among Former Elite Athletes

Presenter: Camilo Fernandez

A cross-sectional study assessed the link between body roundness index (BRI) and subclinical atherosclerotic cardiovascular disease (ASCVD) risk, measured by coronary artery calcium (CAC) burden, in 923 retired National Football League players (mean age 58.2 ± 9.1 years).

BRI (mean 5.4 ± 4.8) was significantly associated with CAC burden, across all risk categories (odds ratio, OR 1.21; p=0.04 in mildly increased category; OR 1.59; p<0.01 in moderately increased category), with two-fold higher odds in moderate-to-severely increased category (OR 2.31; p<0.01). However, body mass index (BMI) was only linked to moderate risk category (OR 1.18; p=0.03). These findings suggested BRI may better reflect ASCVD risk in former athletes versus BMI. 

CagriSema Reduces Blood Pressure in Adults With Overweight or Obesity: The REDEFINE 1 Trial

Presenter: Morten Bottcher

In the REDEFINE 1 phase 3 trial, 3417 adults with overweight or obesity were randomized to receive once-weekly CagriSema 2.4 mg/2.4 mg, semaglutide 2.4 mg, cagrilintide 2.4 mg, or placebo for 68 weeks.

The mean (±SD) BMI was 37.9 ± 6.7, systolic blood pressure (SBP) was 127.1 ± 14.2 mmHg, and diastolic blood pressure (DBP) was 82.1 ± 9.2 mmHg. CagriSema reduced systolic blood pressure (SBP) by 10.9 mmHg and diastolic blood pressure (DBP) by 5.3 mmHg, outperforming all comparators (p<0.01). Effects were consistent across baseline body mass index (BMI) subgroups. At baseline, 36.3% of the participants had hypertension. Among participants on antihypertensive medication, 39.6% in the CagriSema group reduced or discontinued use vs. 18.8% with placebo.These findings highlight a significant antihypertensive benefit of CagriSema in obesity management, warranting further mechanistic investigation.

Effect of CagriSema 2.4mg/2.4mg on Body Composition, Muscle Strength & Physical Function: REDEFINE 1

Presenter: Cynthia Karenina Osorto Contreras

In the REDEFINE 1 phase 3a trial, 3417 adults with overweight or obesity received once-weekly subcutaneous CagriSema 2.4 mg/2.4 mg or comparators for 68 weeks. 

Muscle strength was assessed by STS (Sit-to stand) test and there was no difference between Cagrisema vs Placebo (2.5 vs 2.4 repetitions; p=0.92). CagriSema led to a weight reduction of −22.7% (−24.1 kg) overall at week 68. Among 252 participants with dual-energy X-ray absorptiometry (DXA) scans, CagriSema led to a mean weight loss of 26.6 kg, with 67% from fat mass and 33% from lean soft tissue. For those with DXA scan, change in fat mass was -36% vs -13.1% and change in lean mass was -24% vs -7.2%, respectively, Despite lean mass reduction, its proportion increased, indicating improved body composition. Physical function scores improved significantly: IWQOL–Lite–CT (+26.9 vs +14.1 placebo) and SF-36v2 (+7.4 vs +3.4 placebo; p<0.001). 

Improvements in Glycemic Parameters and Cardiovascular Risk Factors with Oral Semaglutide 25 mg

Presenter: Domenica M. Rubino

An exploratory analysis of OASIS 4 study evaluated the impact of weight loss with oral semaglutide 25 mg or placebo, plus lifestyle intervention, for 64 weeks in 307 overweight/obese adults (BMI≥30 kg/m2 (or ≥27 kg/m2 with ≥1 obesity-related comorbidity).

Oral semaglutide 25 mg led to significant improvements in glycemic and CV risk factors, especially among those with ≥15% weight loss. Half of the patients on semaglutide reached this threshold versus 5.6% on placebo. In semaglutide group, participants who achieved ≥15% had numerically Greater reductions in fasting insulin, fasting plasma glucose, glycated hemoglobin, BP, CRP, non-HDL cholesterol, and triglycerides. More prediabetics on semaglutide with ≥15% weight reduction achieved normoglycemia vs. those with <15% weight reduction (92.5% vs. 54%). 

ObesityWeek 2025, 4th – 7th Nov 2025, Atlanta, GA.