Effective treatment for clinical obesity is available but is rarely offered by healthcare systems, which often treat complications without treating the underlying cause. The LightWAY trial will investigate the clinical benefits and harms as well as cost-effectiveness of an intensive weight loss intervention compared with existing weight management programmes for people with clinical obesity.

LightWAY is an investigator-initiated, international, randomised, parallel-group clinical superiority trial with blinded outcome assessment. Six hundred people seeking treatment for clinical obesity (body mass index ≥35 kg/m² with comorbidities) will be recruited in centres in the UK and Denmark and randomised 1:1 to one of two groups. The experimental group will be offered a 2-year intensive weight loss programme providing support and advice to follow a total diet replacement programme, followed by gradual transition to an energy-reduced diet in combination with increased physical activity and if needed, prescription of weight loss medication. The control group will receive usual care, typically comprising brief behavioural support for weight loss and treatment of the complications of obesity or occasionally referral to specialist weight management services. The two co-primary outcomes are cardiometabolic risk, assessed with metabolic syndrome severity Z-score, and body weight assessed at 2 years. The secondary outcomes include the Short Form-36 mental component scale, 4-metre gait speed and proportion of participants achieving ≥20% weight loss. The key adverse effects will be the proportion of participants with at least one serious adverse event, incidence of eating disorders and disproportional loss of bone mass. Incremental cost-effectiveness will be assessed over the trial period and over the lifetime through modelling.

Ethical approval was granted in the UK (August 2024, 24/SC/0211) and Denmark (December 2023, H-23065222). Findings will be disseminated through peer-reviewed journals and scientific conferences and to participants in the trial and clinicians.

NCT06321458.

The number of people living with obesity is increasing rapidly worldwide, and the WHO estimates approximately 5 million deaths yearly from non-communicable diseases related to elevated body mass index (BMI). The most effective treatment for weight loss is bariatric surgery, but due to the associated risks and the need for lifelong care, this is not a viable treatment for every patient. With the advent of gut-hormone-based medications to treat obesity, the effectiveness of non-surgical treatment is approaching that of surgical interventions. We therefore aim to investigate the beneficial and harmful effects of laparoscopic bariatric surgery versus any non-surgical treatment.

We will conduct a systematic review with meta-analysis applying our eight-step procedure to assess thresholds for clinical significance and trial sequential analysis to mitigate the risk of random errors. To identify relevant trials, we will search for both published and unpublished trials, without any language restriction, in major medical databases (CENTRAL, MEDLINE, EMBASE, LILACS, SCI-EXPANDED and CPCI-S) and trial registries. The date range covered by the search is from database inception until final search date—within 3 months prior to submission of final results manuscript. Two review authors will independently screen references, extract data and perform risk-of-bias assessment using the Cochrane Risk of Bias Tool 2 and the Grading of Recommendations, Assessment, Development and Evaluations. We will include randomised clinical trials comparing laparoscopic surgery currently in use with any non-surgical comparator in adults or adolescents with BMI >30 kg/m². Quasi-randomised studies or non-randomised studies will not be included. Our critical outcomes are all-cause mortality, serious adverse events and quality of life, and our important outcomes are major cardiovascular events, weight at follow-up, physical function and glycaemic control. In addition, we have two explorative outcomes: metabolic syndrome or Z-score and reported incident of alcohol abuse or other addictive disorder or self-inflicted harm.

This review will collect and perform secondary analysis of data from publicly available sources and ethical approval is therefore not required. The findings will be published in peer-reviewed journals and presented at relevant scientific conferences. We will strive to publish with open access. Awareness will be made through social media platforms. This review aims to help clinicians in identifying best practices in the wide-spanning field of obesity treatment.

CRD420251135341.