Abstract
Individuals with excess weight face an elevated risk for various physical and mental health conditions. Interventions targeting weight loss can improve health, with modest weight loss of five to ten percent of body weight often considered clinically meaningful for enhancing health outcomes. However, the benefits of achieving low-level weight loss (<5% body weight) are poorly understood. A systematic review of relevant literature synthesized the evidence that assessed the potential health benefits of losing less than five percent body weight. Searches of seven academic databases included studies in any language, from any country, with no time constraints. Any intervention studies that assessed the impact of less than five percent weight loss on any measured physical or mental health markers or indices were included. Seventy studies from 68 articles were included, with study participants ranging from 14 to 10,742. In total, 137 health markers were assessed, categorized into metabolic markers (n = 42), cardiovascular markers (n = 32), anthropometric measures (n = 19), quality of life indices (n = 10), inflammatory biomarkers (n = 10), renal and hepatic markers (n = 9), psychosocial and behavioural measures (n = 8), pulmonary function (n = 3), total mortality (n = 2), ovulatory function (n = 1), and muscle strength (n = 1). Overall, 60% of studies reported improvements, 37% found no change or mixed results, and 3% observed a worsening of health markers or indices. Based on the available data, 87% of participants (n = 15,839) in the studies reported improvements in health markers or indices as a result of low-level weight loss.
Introduction
Individuals with excess weight, compared to those with a healthy weight, are at an increased risk for many diseases and chronic health conditions including cardiovascular diseases, type 2 diabetes, some types of cancer, anxiety and depression. Such comorbidities can result in reduced mobility, chronic pain, and diminished quality of life. Obesity is associated with psychosocial difficulties, including lower self-esteem, heightened stress levels, eating disorders, as well as increased vulnerability to mental health disorders. People living with excess weight often face stigma and discrimination, which can result in self-stigmatisation, isolation and self-devaluation. Obesity is also associated with substantial social and economic consequences. In the United Kingdom (UK), it is estimated that by 2050, overweight and obesity will cost the National Health Service £10 billion per year, with wider costs to society and business projected to reach £49.9 billion per year.
Interventions targeting weight loss can improve health and prevent obesity-related co-morbidities. Weight loss among individuals with excess weight can have beneficial effects on cardiovascular disease, type 2 diabetes, sleep apnoea, chronic kidney disease, hypertension, and dyslipidaemia. Guidelines from the UK and United States of America recommend achieving modest weight loss, ranging from five to ten percent, in order to yield clinically meaningful improvements in health outcomes. As a result, weight loss of more than five percent is often cited as a key threshold for achieving clinically significant impacts and is commonly used as a target or benchmark in weight management services. While the five percent threshold provides a practical goal for weight management interventions, many participants engaging in a 12-week lifestyle intervention will not achieve this threshold. The implications of achieving a body weight reduction of less than five percent are poorly understood. Currently, interventions resulting in less than five percent weight loss are often deemed ineffective; however, they may still offer benefits in improving health outcomes, particularly for individuals living with obesity. Exploring the potential health impacts of less than five percent weight loss, could be useful in informing policy and practice.
Methodology of the Systematic Review
This systematic review was registered with PROSPERO (CRD42023406342) conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. To be eligible for inclusion, studies needed to be randomised or quasi-randomised controlled trials (RCTs) or intervention studies with pre-post measures. The included exposures were weight loss interventions with lifestyle (physical activity/diet) or pharmacological components. The participant criteria were adults (18 years or older) who lost less than five percent of their body weight following an intervention. Included outcomes were any type of health measures, including physical, mental, or behavioural. The health measures of interest were broad, and searches were structured without outcome terms to ensure all relevant outcomes were captured. Findings were required to be stratified by percentage weight loss. Studies from any country, language or published at any time were included. Studies were excluded if they were non-peer reviewed articles (dissertations, conference abstracts, grey literature), if they did not include any relevant health measures, if they only presented outcomes by overall weight change (without any stratification by percentage weight loss), or if the weight loss intervention was surgical. Surgical interventions, including bariatric surgery, were excluded due to the difference in intervention intensity and the percent weight loss typically observed (typically 20 to 30% weight loss).
Searches of the following electronic databases were conducted in March 2023: Medline (Ovid), Embase (Ovid), PsycINFO (Ovid), CINAHL (Ebsco), Cochrane Library CENTRAL, Applied Social Sciences Index and Abstracts (ProQuest), and Web of Science-Social Science Citation Index and Emerging Sources Citation Index. The search strategy was developed by JP with oversight and input from CS (information specialist). The searches were conducted by JP and the results were firstly imported into EndNote version 20 to remove duplicates, before importing into EPPI-Reviewer Version 6 software to again remove duplicates and for screening and review management. Articles were double screened on title and abstract and full text by a team of reviewers (JP, SM, JC) and discrepancies were jointly reconciled.
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Assessment of Quality and Data Extraction
The Critical Appraisal Skills Programme (CASP) checklist was used to assess the bias in the included studies. Bias assessment for each article was conducted independently in duplicate by a team of reviewers (JP, SM, DD) with discrepancies jointly reconciled. Studies were categorised as having a high, moderate or low risk of bias.
Data were extracted for participants achieving less than five percent weight loss, which may have been the whole study population or, more often, a subset of the original study population. Reported sample sizes reflect the groups relevant to the research question, often subgroups of whole study cohorts. Data extracted included study characteristics (primary author, country, year of publication), participant characteristics where possible (sample size, stratified sample size, age, baseline BMI, comorbidities), intervention characteristics (intervention type, duration, follow up), outcome details (category, measure, key finding). Corresponding authors were contacted to request additional data, where required, for the meta-analysis. Eight studies’ corresponding authors were contacted, of whom two responded with the required data. Mean score change, effect size measurements (e.g., standard deviation), and stratified sample sizes were specifically requested.
Data Synthesis
Findings across included studies were synthesised narratively. Due to the heterogeneity and constraints on the available data, meta-analysis was not possible. The data presented several constraints, such as outcomes being stratified by different weight-loss groups and values being inconsistently reported. Few studies reported the overall baseline values, while other studies reported the values by intervention group. Follow-up outcomes were also often reported only by weight-loss groups. Additionally, there were missing sample sizes and precision estimates, which further complicated the analysis.
Study characteristics were tabulated, and health markers and indices, identified across the included studies, were classified into broader health categorises. The health markers and indices were categorised as metabolic markers, cardiovascular markers, anthropometric markers, quality of life indices, inflammatory biomarkers, renal and hepatic markers, psychosocial and behavioural measures, pulmonary function, total mortality, ovulatory function, and muscle strength.
Additionally, the findings for each study were classified into: ‘improvements’ where all studied health measures showed improvements either statistically significant or not, ‘mixed results’ where the studied health measures either showed no significant change or a mixture of improvements and declines; and ‘worsening’ where all the studied health measures that showed either statistically significant or non-significant deterioration. The overall impact of weight loss interventions on health measures of participants that loss less than five percent body weight in each study included was considered. Findings by follow-up duration were considered to assess impacts on health measures, over time. Studies with less than 6 months follow up were first compared to those with 6 months or greater, and then studies with less than 12 months follow up to those with 12 months or greater.
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Study Selection Results
The searches resulted in 13,905 articles, of which 5778 were duplicates, leaving 8127 original articles to screen on title and abstract. After screening on title and abstract, 7158 were excluded (3943 manually and 3215 excluded by the machine learning predictive algorithm) and 969 articles were included for full-text screening, of which 11 reports were not retrieved in full-text. Application of the classifier provided articles with scores ranging from 6 to 92 which were sorted in descending order and articles with a score of 70+ were double screened; no articles were included through this process. Studies with a score between 60-69 were screened on title and abstract by one reviewer and no relevant papers were found. 891 articles that did not meet the inclusion criteria for publication type, study design, age of participants, exposure, outcome measure and stratification of results were excluded. This led to the final inclusion of 70 studies from 68 articles.
Quality and Characteristics of Included Studies
Overall, the studies were predominantly assessed as having a moderate risk of bias (n = 36; 53%), followed by high (n = 18; 26%) and low (n = 14; 21%). The typical issues were around randomisation methodology.
Of the 70 included studies, the majority were randomised controlled trials (n = 47); the remaining study designs (n = 23) included before-after non-randomised intervention studies, clinical trials, cohort studies, prospective studies, and secondary analyses of trials/interventions. Most studies (n = 63) were conducted in high-income countries, including the USA (n = 34), UK (n = 3), Canada (n = 3), Japan (n = 3), and Australia (n = 2). Total study participants in the included studies ranged from 14 to 10,742. Follow-up periods ranged from six weeks to 7.4 years, with the majority of the studies (n = 54) having follow-up periods of 12 months or less.
Various intervention types were assessed but were predominantly lifestyle interventions (n = 47), with fewer studies assessing pharmacological only interventions (n = 2) or a combination of lifestyle and pharmacological (n = 21). Lifestyle interventions typically included components focussed on calorie restriction, physical activity promotion programmes, behavioural modifications, or lifestyle counselling. The most common drug utilised for pharmacological interventions were Orlistat (n = 6), Sibutramine (n = 4) and Metformin (n = 2).
The weight loss stratifications in included studies were most commonly less than five percent (n = 44), less than three percent (n = 7), or greater than two percent to less than five percent (n = 7). Studies were described based on their average baseline BMI into categories including overweight and higher (n = 42), obesity class-1 and higher (n = 9), and obesity class-2 and higher (n = 1), with 18 studies not reporting baseline BMI values. Study cohorts were also described based on inclusion criteria for co-morbidities, with the majority not including co-morbidities (n = 39), followed by metabolic syndrome (n = 18), diabetes (n = 8), and hepatic disorders (n = 6).
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Overall Impact on Health Measures
While statistically significant improvements were highlighted, non-significant improvements were classified as improvements. Low levels of weight loss, such as a 0-2% reduction in body weight, can lead to small improvements in health outcomes that may not reach statistical significance, particularly in small studies. A total of 201 unique health markers and indices were reported across the 70 included studies. A total of 11 health categories classified health measures, including health markers and indices. These categories were reported a total of 137 times across the 70 studies: metabolic markers (n = 42), cardiovascular markers (n = 32), anthropometric measures (n = 19), quality of life indices (n = 10), inflammatory biomarkers (n = 10), renal and hepatic markers (n = 9), psychosocial and behavioural measures (n = 8), pulmonary function (n = 3), total mortality (n = 2), ovulatory function (n = 1), and muscle strength (n = 1).
Semaglutide for Weight Loss
Multiple weight loss interventions have been developed during the past decades. Semaglutide, a glucagon-like peptide-1 receptor agonist, is approved to treat type 2 diabetes, with subcutaneous injection doses of 0.25, 0.5, and 1 mg administered once weekly and oral doses of 3, 7, and 14 mg administered once daily. In June 2021, the FDA approved subcutaneous semaglutide for long-term weight management, with higher doses of 1.7 and 2.4 mg once weekly. The Semaglutide Treatment Effect in People With Obesity (STEP) trials have shown the efficacy of semaglutide for the treatment of obesity. In large RCTs, patients receiving semaglutide, 2.4 mg, lost a mean of 6% of their weight by week 12 and 12% of their weight by week 28.
A cohort study, conducted at a referral center for weight management, retrospectively collected data on the use of semaglutide for adults with overweight or obesity between January 1, 2021, and March 15, 2022, with a follow-up of up to 6 months. A total of 408 patients with a body mass index (BMI) of 27 or more were prescribed weekly semaglutide subcutaneous injections for 3 months or more. The primary end point was the percentage of weight loss. The study included 175 patients (132 women [75.4%]; mean [SD] age, 49.3 [12.5] years; mean [SD] BMI, 41.3 [9.1]) in the analysis at 3 months and 102 patients at 6 months. The mean (SD) weight loss after 3 months was 6.7 (4.4) kg, equivalent to a mean (SD) weight loss of 5.9% (3.7%) (P < .001), and the mean (SD) weight loss after 6 months was 12.3 (6.6) kg, equivalent to a mean (SD) weight loss of 10.9% (5.8%) (P < .001 from baseline). Of the 102 patients who were followed up at 6 months, 89 (87.3%) achieved weight loss of 5% or more, 56 (54.9%) achieved weight loss of 10% or more, 24 (23.5%) achieved weight loss of 15% or more, and 8 (7.8%) achieved weight loss of 20% or more. The results of this cohort study suggest that weekly 1.7-mg and 2.4-mg doses of semaglutide were associated with weight loss similar to that seen in randomized clinical trials.
Intentional Weight Loss and Mortality Risk
Globally, 2.6 billion people live with overweight or obesity. In the United States, the age-adjusted prevalence of obesity among adults is 42%, and it is 44% among women 60 years or older. The increasing prevalence of obesity is concerning because obesity raises the risk of type 2 diabetes, cardiovascular disease, certain cancers, reduces quality of life, and shortens life expectancy. Although the association between obesity and adverse health outcomes is well-established, evidence regarding the impact of weight loss on mortality remains inconsistent. Some studies report lower mortality risk among older adults who are overweight or obese compared with those with normal body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) or suggest that weight loss may increase mortality risk. Media reports call this an obesity paradox and suggest to the public that it is healthier to remain overweight rather than to lose weight, generating uncertainty about the benefits of losing weight among older adults.
However, studies about weight loss often have methodological limitations, including lack of data determining whether weight loss was intentional or unintentional, and relying on BMI as the sole measure of obesity. Unintentional weight loss can reflect underlying morbidity or adverse effects of treatment and, thus, can contribute to reverse causality in observational studies. Although weight loss efforts are encouraged in clinical settings and have been linked to health advantages, such as improved cardiovascular health, or lower obesity-related cancer incidence, whether intentional weight loss reduces mortality risk is not well understood.
A cohort study of 58 961 women aged 50 to 79 years at baseline, intentional efforts at weight reduction coupled with measured reduction in waist circumference was associated with significantly lower mortality risk over 18.6 years of follow-up for all-cause, cancer, and cardiovascular mortality. These findings suggest that weight loss efforts for women should focus on lifestyle changes that will result in clinically meaningful reductions in visceral adiposity as measured by waist circumference. This cohort study used data from the Women’s Health Initiative Observational Study, which had a prospective cohort with mean follow-up of 18.6 years ending in February 2023. The study included women aged 50 to 79 years at 40 clinical centers in the US. Women with missing data, cancer at baseline, or considered underweight at baseline were excluded. Outcomes included adjudicated all-cause, cancer, cardiovascular, and other mortality through the end of follow-up.
This study included 58 961 women at baseline (mean [SD] age, 63.3 [7.2] years; mean [SD] BMI, 27.0 [5.6]; mean [SD] WC, 84.1 [13.0] cm). As of February 28, 2023, 29 183 women (49.5%) died from all causes. Intentional weight loss measured by questionnaire was associated with lower subsequent mortality rates for all-cause mortality (HR, 0.88; 95% CI, 0.86-0.90), cancer mortality (HR, 0.87; 95% CI, 0.82-0.92), cardiovascular mortality (HR, 0.87; 95% CI, 0.83-0.91), and other mortality (HR, 0.89; 95% CI, 0.86-0.92), comparing loss of 5 pounds or more to stable weight. Reported intentional weight loss coupled with actual weight reduction of 5% or more was associated only with lower cardiovascular mortality (HR, 0.90; 95% CI, 0.81-0.99). Reported intentional weight loss coupled with measured WC loss was associated with lower rates of all-cause mortality (HR, 0.91; 95% CI, 0.86-0.95), cancer mortality (HR, 0.85; 95% CI, 0.76-0.95), and cardiovascular mortality (HR, 0.79; 95% CI, 0.72-0.87). In this cohort study, reported intentional weight loss efforts that were coupled with measured WC reductions were associated with lower risk of all-cause, cancer, and cardiovascular mortality. Attention to diet and exercise that promote reductions in central adiposity should be encouraged.
Benefits of Modest Weight Loss
Overweight and obese individuals are frequently encouraged to lose 5-10% of their weight and are told that weight losses of that magnitude will help improve their cardiovascular disease (CVD) risk factors. The Look AHEAD (Action for Health in Diabetes) provides a unique opportunity to carefully assess the effects of modest weight loss on CVD risk factors in individuals with type 2 diabetes, a population at high risk for CVD. Look AHEAD is a multicenter, randomized clinical trial examining the long-term effects of lifestyle interventions on cardiovascular morbidity and mortality in 5,145 overweight or obese participants with type 2 diabetes who were randomly assigned to intensive lifestyle intervention (ILI) or to usual care, referred to as diabetes support and education (DSE).
The magnitude of weight loss at 1 year was strongly (P < 0.0001) associated with improvements in glycemia, blood pressure, tryiglycerides, and HDL cholesterol but not with LDL cholesterol (P = 0.79). Compared with weight-stable participants, those who lost 5 to <10% (7.25 ± 2.1 kg) of their body weight had increased odds of achieving a 0.5% point reduction in HbA1c (odds ratio 3.52 [95% CI 2.81-4.40]), a 5-mmHg decrease in diastolic blood pressure (1.48 [1.20-1.82]), a 5-mmHg decrease in systolic blood pressure (1.56 [1.27-1.91]), a 5 mg/dL increase in HDL cholesterol (1.69 [1.37-2.07]), and a 40 mg/dL decrease in triglycerides (2.20 [1.71-2.83]).