ABSTRACT While GLP‐1 and GIP receptor agonists like semaglutide and tirzepatide have revolutionized pharmacologic obesity treatment, metabolic and bariatric surgery (MBS) continues to demonstrate superior weight loss and cost‐effectiveness. Current evidence shows tirzepatide outperforms semaglutide with over 20% weight reduction, yet most clinical trials lack ethnic diversity, limiting the generalizability of these outcomes. This is a retrospective, single‐centre study that evaluates 12‐month weight loss results comparing tirzepatide and SG within a diverse, urban patient population. 12‐month weight loss outcomes were compared between patients receiving tirzepatide and those undergoing sleeve gastrectomy (SG). Primary endpoints included changes in BMI, excess weight loss and total weight loss (TWL) percentage at 3, 6 and 12 months, following ASMBS reporting standards to evaluate treatment efficacy and comparative outcomes. Linear mixed models revealed statistically significant differences in weight loss between SG and tirzepatide cohorts across all time points ( p < 0.001). By 12 months, the SG group was associated with greater weight loss than tirzepatide in this selected matched cohort with a 30% TWL and a 12 kg/m 2 BMI reduction, compared to 12% TWL and 7 kg/m 2 for tirzepatide. SG was associated with greater weight loss than tirzepatide in this selected matched cohort, especially for eligible patients in ethnic minority groups. However, tirzepatide serves as a vital non‐invasive alternative, requiring individualized treatment decisions based on patient preference, cost and specific metabolic goals.
An international cohort of 161 clinicians and researchers from 19 countries attended the 3rd International Meeting on Pathway-Related Obesity: Vision & Evidence (IMPROVE) in Prague, Czech Republic, on 2-4 July 2025. The aims of the meeting were to advance understanding of hyperphagia and obesity caused by defects in the melanocortin-4 receptor (MC4R) pathway and to support peer-to-peer sharing of clinical experience and emerging evidence. The programme comprised four sessions covering hyperphagia, monogenic MC4R pathway diseases, Bardet-Biedl syndrome and acquired hypothalamic obesity. Discussions focused on defining and measuring hyperphagia, updates in genetic diagnostics and natural history, real-world and trial data on targeted therapies and practical multidisciplinary models of care with earlier intervention. Patient and caregiver quality of life remained central throughout. These Proceedings summarise the key updates, discussions and initiatives generated at IMPROVE 2025.
Obesity is associated with adverse retinal microvascular changes, including narrower central retinal arteriolar equivalent (CRAE), wider central retinal venular equivalent (CRVE) and lower arteriovenous ratio (AVR). Although bariatric surgery improves cardiometabolic risk, its effect on retinal microvascular calibre remains uncertain. We systematically searched the Cochrane Library, PubMed, ScienceDirect and Scopus up to June 2026. Prospective cohort studies reporting CRAE, CRVE or AVR before and after bariatric surgery in patients with obesity were included. Risk of bias was assessed using the Newcastle-Ottawa Scale. Pooled mean differences (MD) with 95% confidence intervals (CI) were calculated using a random-effects model. Eight prospective cohort studies including 283 patients were included. Seven studies contributed to the CRAE and CRVE analyses, and seven contributed to the AVR analysis. Bariatric surgery was associated with a significant increase in CRAE (MD = +4.02 μm, CI [0.26-7.78], p = 0.04). Sensitivity analysis excluding one study showed a stronger and more consistent effect (MD = +5.41 μm, CI [4.59-6.22], p < 0.01). CRVE significantly decreased after surgery (MD = -6.75 μm, CI [-7.42 to -6.07], p < 0.01), while AVR significantly increased (MD = +0.03, CI [0.02-0.05], p < 0.01). Sensitivity analyses suggested that the direction of effect was generally robust, although between-study heterogeneity was present. Bariatric surgery may be associated with favourable retinal microvascular changes in patients with obesity, reflected by increased CRAE and AVR and decreased CRVE.
This systematic review and meta-analysis aimed to compare the efficacy and safety of tirzepatide versus semaglutide for weight reduction in adults with overweight or obesity. We included randomised controlled trials and observational studies comparing tirzepatide and semaglutide with ≥ 24 weeks of follow-up. The primary outcome was percentage weight change from baseline. Secondary outcomes included absolute weight change, weight-loss thresholds, HbA1c and safety outcomes. Ten studies including 41 381 participants were analysed. Tirzepatide was associated with greater percentage weight reduction than semaglutide (MD -4.28 percentage points; 95% CI -5.28 to -3.28; p < 0.00001) and greater absolute weight loss (MD -4.43 kg; 95% CI -5.56 to -3.30; p < 0.00001). Tirzepatide was also associated with a higher likelihood of achieving ≥ 10%, ≥ 15% and ≥ 20% weight loss, with no difference at ≥ 5%. HbA1c reduction was greater with tirzepatide (MD -0.29%; p = 0.0002). Subgroup analyses by study design and type 2 diabetes status yielded consistent findings. There was no significant difference in treatment discontinuation due to adverse events (RR 1.28; p = 0.54), whereas serious adverse events were more frequent with tirzepatide (RR 1.83; p = 0.007). Overall and gastrointestinal adverse events were similar between groups. Tirzepatide was associated with greater weight reduction, greater glycaemic benefit and a higher likelihood of achieving weight-loss thresholds than semaglutide, but with a higher risk of serious adverse events.
To investigate differences in cause-specific mortality risks between obesity classes stratified by age and sex, using a nationally representative sample of the US population. Differences in mortality risk by standard body mass index (BMI) categories with examination of Obesity Classes I-III, stratified by age (less or more than 65 years) and sex were examined using Cox proportional hazard ratios with data from NHANES Continuous (1999-2018) with mortality follow-up through 31 December 2019. Among younger adults (< 65 years), Obesity Class III was associated with higher all-cause, cardiovascular, non-cardiovascular/non-cancer and diabetes-related mortality compared to Class I. Among older adults (≥ 65 years), there were fewer significant associations with only cardiovascular and diabetes-related mortality risks being elevated in men with Obesity Class III and none in women. There were no differences in mortality risks between Obesity Classes I and II, except for diabetes-related mortality in younger adults and older men. Obesity Class III is strongly associated with higher mortality risk in younger adults (< 65 years) and to a lesser degree in older adults (≥ 65 years). Mortality risks were generally similar between obesity Classes I and II. Therefore, younger adults under 65 years of age with severe obesity may benefit more from aggressive obesity management.
