The latest evidence and guidance in lifestyle and surgical interventions to achieve weight loss in people with overweight or obesity

Monday, March 3, 2025 – ABSTRACT
Background
The prevalence of obesity and related co-morbidities has reached epidemic proportions. Effective evidence-based treatment approaches are therefore important. Lifestyle intervention remains the mainstay of the treatment strategy to manage obesity. Increased evidence has also emerged regarding the efficacy of metabolic bariatric surgery (MBS) to induce significant and sustained weight loss while also reducing the progression of obesity-related co-morbidities for people living with obesity.
Aims & Methods
This article aims to bring together current evidence, guidance and best practice for the prevention and management of people living with overweight or obesity by means of lifestyle and behavioural intervention, as well as by MBS.
Result
Lifestyle intervention encompasses dietary strategies, physical activity and behavioural intervention. Discussion on MBS will focus on current indications, comparison between different MBS procedures, novel endoscopic techniques, potential complications and pre-operative management.
Plain Language Summary
The number of people living with excess weight and complications associated with being overweight is alarmingly quite high. Effective treatment approaches that are supported by clinical studies are therefore important. Lifestyle changes remain very important to manage excess weight. Increased evidence has also shown the benefits of weight loss surgery to produce significant weight loss which could be sustained, while also reducing the risk of developing medical conditions associated with excess weight. This article aims to bring together current evidence, guidance and best practice for the prevention and management of people living with excess weight by means of lifestyle and behavioural changes, as well as by weight loss surgery. Lifestyle intervention encompasses dietary strategies, physical activity and behavioural intervention. Discussion on weight loss surgery will focus on current criteria for suitability, comparison between different weight loss surgery procedures, new techniques, possible complications and appropriate management prior to weight loss surgery.

The safety, tolerability, pharmacokinetics and pharmacodynamics of GZR18 in healthy American and Chinese adult subjects

Monday, March 3, 2025 – Abstract
Aims
GZR18, a novel long-acting GLP-1 receptor agonist, has demonstrated substantial metabolic improvements in diabetic and obese animal models. The present studies aimed to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of the ascending dose of GZR18 in healthy American and Chinese subjects.
Materials and Methods
In these phases 1, randomized, double-blind, placebo-controlled, sequential, dose-escalation US and Chinese studies, healthy American and Chinese adults with similar age were enrolled to once-weekly subcutaneous injection of GZR18 or placebo. The studies included three cohorts of male American subjects (cohorts US-1–3) and six cohorts of Chinese subjects (cohorts CN-1–6, male and female), each with a specified target dose of GZR18 ranging from 1 to 50 μg/kg (1–10 μg/kg for US study and 5–50 μg/kg for Chinese study). The primary endpoints were the safety and tolerability of GZR18. Blood samples were collected for PK and PD analysis of GZR18 before and after dosing. A population PK analysis of GZR18 was conducted to ascertain whether there are ethnic PK differences between American and Chinese adults.
Results
The exposure of GZR18 was comparable between healthy American and Chinese subjects, with the geometric mean ratio between the two populations for AUC0-t and C
max close to 1. A dose-dependent increase in AUC0–t and C
max occurred in both populations. The median time to maximum plasma concentrations (T
max) in American subjects ranged from 72 to 96 h, and the mean T
max ranged from 60 to 72 h in Chinese subjects. The half-life of GZR18 was approximately 7 days in both American and Chinese subjects. Evident body weight reduction was observed in GZR18 treatment groups in Chinese subjects (cohorts CN-3–6 on Day 15, −1.25 to −1.86 kg; −1.88% to −3.11%). No deaths, serious adverse events or hypoglycaemia were reported. Decreased appetite and nausea were the most frequently reported treatment-emergent adverse events, observed in Chinese study and mild in severity. The safety profile of GZR18 was generally consistent with the same class of drugs.
Conclusions
GZR18 demonstrates good tolerability in healthy American and Chinese subjects. No ethnic differences were observed between healthy American and Chinese subjects. The safety, PK and PD profiles of GZR18 support its further clinical evaluation for glycaemic and body weight control.