Body Composition (DXA) Changes During 6-Month Withdrawal from Semaglutide and/or Bimagrumab Treatment of Adults with Obesity: The BELIEVE Study Extension

Presenter

Aronne, L. J

Bimagrumab (bima), an antibody to activin type 2 receptors, blocks activin/myostatin pathways, increasing skeletal muscle and reducing fat mass; in combination with semaglutide (sema), a GLP‑1RA, additive fat loss and muscle preservation have been observed.  

BELIEVE was a Phase 2, double-blind, placebo-controlled trial involving 507 adults with overweight or obesity. Participants were randomized into nine groups: placebo; bima monotherapy (10 or 30 mg/kg IV every 12 weeks); sema monotherapy (1.0 or 2.4 mg SC weekly); and their respective combination regimens. After 48 weeks, open-label active treatment continued through week 72, followed by post-treatment follow-up to week 104. Total body fat mass, lean mass, and estimated abdominal visceral adipose tissue (VAT) were assessed by DXA throughout the study, including at week 96 

At Week 72, % change in weight was −10.8% (bima 30), −15.7% (sema 2.4), −22.1%; fat mass −28.5%, −27.8%, −45.7%, respectively. Lean mass increased with bima, decreased with sema, and was largely preserved with combined treatment. VAT reduction was greater with bima 30 (−45.1%) vs sema 2.4 (−35.8%) and further reduced (−58.2%). At Week 96 (N=288), weight change was −9.0% vs −9.1%, indicating greater regain after sema withdrawal. Fat mass remained −18.8% vs −17.7%. Lean mass gains with bima (+2.5%) reversed (−2.1% vs BL), while sema-associated loss (−7.4%) partially recovered (−4.1% vs BL). 

Following 6-month treatment withdrawal, lean mass returned to baseline post-bima, as expected. Partial weight regain after semaglutide withdrawal showed a similar fat:lean ratio as weight loss, suggesting no preferential fat regain.

Semaglutide Reduces Body Weight Regardless of Menopause Status: STEP and OASIS 4 Post Hoc Analysis

Presenter

Palacios, S

This post hoc analysis of Semaglutide Treatment Effect in People with obesity (STEP)  (n=2151) and Oral Semaglutide in Adults with Overweight or Obesity (OASIS 4)  (n=151) trials evaluated semaglutide (2.4 mg weekly s.c. for 68 weeks; 25 mg oral daily for 64 weeks) on anthropometric outcomes in women with overweight/obesity without diabetes, stratified by menopause status.This was determined based on the response to “Has the participant gone through menopause?”, medical history, and age. Pre-menopause pts responded “No,” had no history of menopause, and were aged <45 years; peri-menopause pts responded “No,” had no history of menopause, and were aged 45–54 years; post-menopause pts either responded “Yes,” had documented menopause, or were aged ≥55 years. 

In STEP, median body weight reduction was −18.0%, −17.7%, and −16.4% in the pre-, peri-, and post-menopause groups, respectively; similar trends were observed in OASIS 4 (−18.1%, −15.6%, −15.6%). The proportion achieving ≥10% weight loss in STEP was 74.7%, 78.7%, and 74.8%, and in OASIS 4 was 65.1%, 77.4%, and 63.3% across the respective groups. Waist circumference decreased by −18.5, −17.7, and −15.9 cm in STEP and −17.7 (13.5), −15.3 (8.6), and −13.5 (10.3) cm in OASIS 4. WHtR risk improvement reached 17.1%, 14.2%, and 9.1% in STEP and 19.0%, 9.7%, and 8.3% in OASIS 4, respectively. 

Semaglutide produced clinically meaningful, consistent weight loss and anthropometric improvements irrespective of menopause status. 

Orforglipron for the Maintenance of Body Weight Reduction Achieved with Injectable Therapy: ATTAIN-MAINTAIN Trial

Presenter

Aronne, L. J.

This phase 3b, randomized, double‑blind trial evaluated once‑daily oral orforglipron (non‑peptide glucagon‑like peptide‑1 receptor agonist) versus placebo in adults who had completed 72 weeks of tirzepatide or semaglutide, to maintain prior weight loss. Post-treatment with Tirzepatide or Semaglutide, participants are randomly assigned to orforglipron MTD (24 or 36mg) or placebo.

Participants switching to orforglipron largely maintained weight reduction achieved with injectables. Participants treated with tirzepatide had mean BW of 115.8 kg at SURMOUNT‑5 baseline, 90.3 kg at Week 72, and 95.9 kg at the end of ATTAIN‑MAINTAIN; corresponding values with semaglutide were 113.5, 94.3, and 95.9 kg.Maintenance was slightly greater after semaglutide. Visceral fat channges were similar. Gastrointestinal adverse events were common but mostly mild to moderate. 

Orforglipron effectively helps sustain weight loss after injectable therapy and represents a potential option for long‑term weight maintenance.

Effects of Liraglutide Therapy on Mental Health Status of Adolescents with Morbid Obesity

Presenter

Draxler-Dworzak, S.

This prospective study examined the psychological effects of liraglutide in 28 adolescents (12–18 years) with morbid obesity compared to 28 controls over two years with the collection of somatic parameters and standardized psychological parameters score based assessments. 

Early results showed improvements in depressive symptoms in self- and parent-reports (DISYPS-III; 3), emotional and behavioural problems (CBCL, YSR; 4), quality of life (KINDL-R; 5) and obesity-related pathogenic eating behaviours (FEV Path; 5) by 12 weeks. Although effects partially declined by 6 months, outcomes remained better than baseline. Findings suggest liraglutide may provide early psychological benefits, though variability increases over time. Ongoing data collection will strengthen conclusions and address gaps in understanding mental health impacts of GLP-1 therapy in pediatric obesity.

GLP-1 Receptor Agonists and Reductions of Disease Burden in Individuals with Asthma and Either Overweight, Obesity or Type 2 Diabetes: A Nationwide Self-Controlled Study

Presenter: Høj, S.

GLP‑1 receptor agonists (GLP‑1 RAs), widely used for obesity and type 2 diabetes, may also improve asthma outcomes through weight loss, reduced airway inflammation, and better metabolic control. 

In a Danish nationwide self-controlled cohort of 27,523 adults with asthma and comorbid overweight, obesity, or T2DM, initiation of GLP‑1 RAs was linked to a 26% reduction in asthma exacerbations. Secondary outcomes, including reliever use, inhaled corticosteroid exposure, and pneumonia events, also decreased. 

Benefits were consistent across subgroups, suggesting GLP‑1 RAs significantly improve asthma control irrespective of treatment indication. GLP1 RA was associated with significant reductions in exacerbations, reliever use, exposure to ICS and pneumonia in patients with asthma and overweight/obesity/T2DM,  

Preservation of Skeletal Muscle Mass during GLP-1 Receptor Agonist Therapy: An As-Treated Mixed-Effects Analysis by Drug Type

Presenter: Jürets, A.

GLP‑1 receptor agonists (GLP‑1RAs) promote weight loss in obesity, but concerns exist about potential skeletal muscle loss. This retrospective cohort study of 451 individuals compared body composition changes with liraglutide, semaglutide, and tirzepatide using bioelectrical impedance analysis. 

Relative muscle mass slightly increased over time across all agents, with no evidence of accelerated loss. Absolute muscle mass differences between drugs were small (<1 kg). Tirzepatide showed marginally lower relative muscle mass than liraglutide. Overall, findings suggest GLP‑1RAs preserve muscle mass, supporting their metabolic safety without clinically meaningful muscle loss during treatment.

Efficacy and Safety of Oral Orforglipron in Adults Living with Obesity: A Systematic Review and Meta-Analysis

Presenter: Hammad, N.

Orforglipron, a once-daily oral GLP‑1 receptor agonist, was evaluated in a meta-analysis of five randomized trials (4,618 participants) with obesity, with or without diabetes. 

It produced dose-dependent weight loss, exceeding 6 kg in diabetes and nearly 12 kg without diabetes at highest doses, alongside improvements in BMI, waist circumference, and HbA1c (up to −1.29%). Gastrointestinal side effects and discontinuations increased with higher doses, but no rise in pancreatitis was observed. Overall, orforglipron shows effective weight and metabolic benefits with an acceptable safety profile, supporting its potential as an oral treatment option.

Impact of GLP 1 Receptor Agonists on Atherogenic Index of Plasma and Metabolic Profile in Adults Living with Type 2 Diabetes and Obesity

Presenter: Bozkur E.

This study evaluated the effect of GLP‑1 receptor agonists on the atherogenic index of plasma (AIP) in 48 adults with type 2 diabetes and obesity over 3 months. AIP was calculated as the log10[triglycerides/HDL-choleserol (HDL-C)].

Significant reductions were observed in body weight, BMI, fasting glucose, HbA1c, and triglycerides. AIP improved due to a lower triglyceride/HDL ratio, indicating a less atherogenic profile. Liver enzymes also declined. Lipid fractions showed no significant changes, and renal and thyroid function remained stable. 

These findings suggest that GLP 1 RAs may contribute to a less atherogenic cardiometabolic profile, beyond its glycemic control.

Cardiometabolic Impact of GLP-1 Receptor Agonists in Inflammatory Bowel Disease: Evidence from a Systematic Review and Meta-analysis

Presenter: Koufakis, T.

The role of GLP-1 receptor agonists (RAs) in patients living with obesity and inflammatory bowel disease (IBD) is limited. Hence this meta-analysis was done to analyze weight, glycaemic and lipid outcomes in this population. 

A meta-analysis of thirteen studies (n=74,513) in patients with inflammatory bowel disease (IBD), with 9,202 patients receiving GLP-1RA therapy, was conducted. Ulcerative colitis predominated (64.9%), and semaglutide was most used (67%). GLP-1RA initiation led to clinically meaningful weight loss, with pooled data showing a 6.32% reduction. HbA1c improved while lipid changes were mild; although none were statistically significant. Overall, GLP-1RAs appeared effective for weight reduction in IBD.

Beyond Weight Loss: The Effects of Incretin-Based Therapies (IBT) on Behavioral Robustness and Lifestyle Adherence in Adults Living with Obesity

Presenter: Dozzani, I.

A 6‑month prospective, observational study examined whether incretin-based therapies (IBT), including GLP-1 and GLP-1/GIP receptor agonists, facilitate behavioral robustness. Eating behavior architecture was assessed using the Three-Factor Eating Questionnaire, evaluating Cognitive Restraint, Uncontrolled Eating, and Emotional Eating and spontaneous physical activity was objectively measured via daily step counts to capture behavioral integration beyond prescribed exercise interventions. 

IBT combined with behavioral therapy produced notable clinical and behavioral benefits in 40 adults with obesity. Mean body weight decreased by 10.4% (p<0.001). Eating behavior improved: uncontrolled eating scores dropped from 58.2 to 24.5 (p<0.001), cognitive restraint scores rose from 45.3 to 62.1 (p<0.01), dietary adherence reached 88%, and spontaneous physical activity increased by >2,100 steps/day (p<0.05). Along with weight loss, IBT showed improvement in eating behaviour and spontaneous physical activity.

First-Year BMI Change after GLP-1-Based Treatment Initiation and Risk of Subsequent Adverse Clinical Outcomes

Presenter: Wilding, J.

A real-world study evaluated impact of first-year BMI change following GLP-1–based treatment (liraglutide, semaglutide, tirzepatide) on risk of osteoarthritis, chronic kidney disease (CKD), obstructive sleep apnea (OSA) and heart failure (HF). It used data from Optum Market Clarity health records. First-year BMI change was defined as the change from baseline to the mean BMI from 275 to 455 days following initiation.  

GLP-1-based treatment was initiated in 89,718 patients; however, 50.1% of patients discontinued within one year. BMI reductions varied: 27% lost <5%, 22.4% lost 5 to <10%, 14.1% lost 10 to <15%, 15.8% lost ≥15%, while 20.8% gained BMI. BMI reduction ≥15% was linked to lower risks of osteoarthritis (HR 0.63; 95%CI 0.51-0.78), CKD (HR 0.70; 95%CI 0.56-0.88), OSA (HR 0.31; 95%CI 0.23-0.41) and HF (HR 0.68; 95%CI 0.40-1.16) vs. BMI reduction of 0 to <5%. Conversely, BMI gain increased risks (HF HR 1.69; 95%CI 1.26-2.25). The study highlighted the clinical significance of achieving and maintaining weight loss after GLP-1-based treatment initiation. 

Weight Loss and Blood Pressure Reduction with GLP-1 Receptor Agonists and Multi-Hormone Receptor Modulators in Overweight and Obesity: A Meta-Regression Analysis of Phase-3 Clinical Trials 

Presenter: Muskiet, M.

The link between weight loss and BP reduction is complex. The GLP‑1RAs act through both weight‑dependent and independent pathways, that are further complicated by multi‑hormone receptor modulators (MHRMs), also targeting GIP, glucagon, and amylin receptors. A meta‑analysis of 32 phase-3 trials was conducted to study the impact of GLP-1RAs/MHRMs on this link (43,618 adults; mean age 54 yrs, BMI 35.5 kg/m², 50% female, 9.2% with T2DM, median treatment duration; 66 weeks). The baseline SBP of the study population was 128 mmHg, 59% of them had hypertension. 

GLP‑1RAs and MHRMs produced placebo‑adjusted mean weight loss of –10.9% (95% CI –12.1 to –9.7; I²=97.9%) and SBP reduction of –5.2 mmHg (95% CI –5.8 to –4.6; I²=77.8%). As per a meta‑regression analysis, 77% of BP variance could be explained by weight loss with GLP-1RAs/MHRMs (P<0.01), 1% weight loss was associated with reduction of 0.34 mmHg SBP. These findings highlight the clinically meaningful BP‑lowering potential of GLP‑1RAs/MHRMs in obesity management.

Cagrilintide Does Not Affect the Exposure of the Combined Oral Contraceptive Ethinyloestradiol/Levonorgestrel or Gastric Emptying as Measured by the Paracetamol Absorption Test 

Presenter :Van Der Horst, J.

This open‑label one-sequence crossover trial evaluated the effect of once‑weekly cagrilintide 4.5 mg on the pharmacokinetics of oral contraceptive (ethinyloestradiol [EE] 0.03 mg, levonorgestrel [LN] 0.15 mg) and gastric emptying in adult female participants of non-childbearing potential (n=30)  with overweight/obesity (BMI 25-39.9 kg/m²). 

EE exposure AUC_0-24h was 1.10 (90% CI 0.94–1.28) and LN 0.92 (0.72–1.17); post-hoc sensitivity analysis showed EE 1.05 (1.00–1.10) and LN 1.01 (0.94–1.09). No differences were observed in Cmax or Tmax. Gastric emptying was unchanged (paracetamol AUC_0–1h 1.10 95% CI [0.75–1.62]; AUC_0–6h 1.18 [1.06–1.31]). All adverse events were non‑serious, mostly mild–moderate gastrointestinal, with 2 withdrawals. 

Cagrilintide does not meaningfully affect contraceptive exposure or gastric emptying and demonstrates good tolerability. 

Tirzepatide for the Maintenance of Body Weight Reduction in People with Obesity: The SURMOUNT-MAINTAIN Trial

Presenter

Horn, D. B.

SURMOUNT‑MAINTAIN (Study of Tirzepatide [glucose‑dependent insulinotropic polypeptide/glucagon‑like peptide‑1 receptor dual agonist] for weight maintenance) was a Phase 3b randomized trial in adults with obesity (body mass index ≥30 kg/m² or ≥27 kg/m² with complications).  

After 60 weeks of tirzepatide 10/15 mg (maximum tolerated dose [MTD]), participants are randomly assigned to continue MTD, reduce the dose to 5 mg, or switch to placebo for an additional 52 weeks. At Week 112, weight change was −21.9% (MTD), −16.6% (5 mg), vs −9.9% (placebo) (all p<0.001 vs placebo Participants maintained 96.5% of weight loss achieved during the Weight‑Loss Period with tirzepatide MTD, 67.9% and 42.8% of weight loss achieved during the Weight‑Loss Period with 5 mg and placebo, respectively. Rescue therapy was required in 7.9% (MTD) vs 65.9% (placebo). 

Continued tirzepatide, especially at MTD, provides sustained and clinically meaningful weight‑loss maintenance with acceptable safety. Reducing tirzepatide to 5 mg was superior to placebo and may offer an alternative to discontinuation, though benefits varied with some weight regain. 

Real-World Effectiveness and Metabolic Outcomes of Tirzepatide in Adults with Obesity

Presenter: Angelopoulos, N.

This prospective real-world study evaluated tirzepatide in 95 adults with obesity over 6 months. 

Patients experienced significant weight loss (−8.2 kg at 3 months; −16.7 kg at 6 months, ~14% total). Improvements were seen in HbA1c, LDL cholesterol, and liver markers (AST, GGT, HSI), indicating better glycemic, lipid, and hepatic outcomes. Renal function remained stable. Despite heterogeneous patients and variable dose-escalations in routine practice, tirzepatide showed consistent benefits. These findings confirm that the substantial weight loss and metabolic benefits observed in clinical trials translate effectively into real-world obesity care.

Tirzepatide Improves Mental and Psychosocial Health-Related Quality of Life in the Real-World Setting

Presenter: Pérez Pevida

Tirzepatide has shown effective weight loss in overweight/obese patients, with improvement in health-related quality of life (HRQoL). However, there is limited real-world data on mental and psychosocial HRQoL. 

In a 6-month prospective, real-world study in 107 obese/overweight adults with comorbidities, the effect of tirzepatide on HRQoL was evaluated using Short Form Health Survey (SF-36v2), EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L), International Physical Activity Questionnaire (IPAQ), and Impact of Weight on Self-Perception (IW-SP) scale. Tirzepatide 7.5 mg produced a mean weight loss of 18.04 kg (95% achieved ≥5% and 60% achieved ≥15% weight loss). Glycaemic, lipid profiles and HRQoL improved significantly. A statistically significant improvement was observed in the IW-SP, indicating better weight-related self-perception after the treatment.

Patient-reported outcomes showed marked gains across SF-36 domains, EQ-5D-5L dimensions and physical activity scores. Tirzepatide demonstrated robust weight reduction, metabolic improvements, and psychosocial benefits, highlighting its potential to address physical and mental aspects.

Switching to Tirzepatide from a GLP-1 RA Resulted in Weight Reduction: Results from 2 Real-World Databases

Presenter: Gibble, T. H.

Two real-world databases (Optum Market Clarity [MC] and the Healthcare Integrated Research Database [HIRD]) were used to study weight reduction among individuals switching to tirzepatide from a GLP‑1 receptor agonist medication for obesity.

Mean weight loss with tirzepatide was 13.1% (MC) and 12.9% (HIRD). At 12 months, 78.9% (MC) and 83.8% (HIRD) achieved ≥5% weight loss, while 21.1% (MC) and 19.6% (HIRD) achieved ≥20% reduction. 71.5% (MC) and 72.1% (HIRD) of individuals were started on tirzepatide2.5 mg; and 81.3% (MC) and 75.4% (HIRD) were on a ≥10 mg dose. Study highlighted tirzepatide’s effectiveness in real-world settings following GLP-1 RA therapy.

Sequential Swallowable Intragastric Balloon (Allurion) and Low-Dose Tirzepatide Therapy Produces Major Fat Mass–Driven Weight Loss with Excellent Tolerability 

Presenter: Flagiello, L.

Swallowable intragastric balloons and incretin-based therapies are established treatment options for people with obesity. Nevertheless, real-world data on the sequential combination of a swallowable intragastric balloon followed by low-dose dual GIP/GLP-1 receptor agonist (tirzepatide) and their impact on body composition is scarce. 

In a prospective cohort of 79 adults with obesity, a 12‑month program combining a 4‑month swallowable Allurion intragastric balloon and 8 months of low‑dose tirzepatide (2.5–5.0 mg) achieved substantial weight loss. Baseline mean weight for the study participants was 121.65 kg (BMI 40.92 kg/m²); at 12 months, weight decreased to 94.32 kg (BMI 31.59 kg/m²), with mean total-body weight loss (TBWL) of 27.33 kg (22.44%). Fat mass declined by 16.6 kg and 6.97 percentage points, while lean mass (LM) percentage rose by 6.94 points despite a 9.44 kg absolute reduction in LM. No serious adverse events or discontinuations occurred. Low-dose tirzepatide resulted in substantial weight loss predominantly driven by fat mass reduction with good tolerability. 

Real-World Comparison of Short-Term Adverse Events, Treatment Persistence, and Efficacy of Tirzepatide and Semaglutide: A Nationwide Multicenter Study 

Presenter

Hepşen, S.

Currently, there is a dearth of real-world data comparing safety, tolerability, and effectiveness of semaglutide (SEMA) and tirzepatide (TIR) in patients with obesity. This nationwide multicenter study compared short‑term adverse events, discontinuation, body weight loss (BWL), and metabolic outcomes between SEMA and TIR in patients with obesity. 

The study population comprised of 2,549 patients with obesity (SEMA, n=1,434, median treatment duration: 16 weeks; TIR, n=1,115, median treatment duration: 12 weeks). Adverse events, predominantly, gastrointestinal occurred in 50.9% of the patients in the SEMA group and 51.0% in the TIR group (TIR; p=0.524). Treatment discontinuation due to pancreatic events were more frequent with SEMA (p=0.006), others were comparable. At 6 months, patients in the TIR group achieved greater reduction in median BWL, as compared to those in the SEMA group (14.4% vs. 12.6%), with higher proportions of patients achieving ≥5%, ≥10%, and ≥15% loss in the TIR group. Treatment with SEMA was associated with greater reductions in fasting plasma glucose and low-density lipoprotein cholesterol at 6 months, and a modest increase in high-density lipoprotein cholesterol, as compared to TIR. The changes in other glucose and lipid parameters were similar between groups. The median HbA1c reduction at 6 months was −0.9% and −0.8% in the SEMA and TIR groups, respectively. Overall, the tolerability was comparable, but TIR yielded greater early BWL. 

33^rd European Congress on Obesity (ECO 2026), 12^th -15^th May 2026, Istanbul, Turkey.