Abstract
Individuals with excess weight face a heightened 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 aimed to synthesise the evidence that assessed the potential health benefits of losing less than five percent body weight. The review included studies in any language, from any country, with no time constraints. Included were any intervention studies that assessed the impact of less than five percent weight loss on any measured physical or mental health markers or indices. 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 behavioral 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.
A systematic review was conducted to synthesise evidence that assessed the health benefits of losing less than five percent body weight on health outcomes or indicators such as, cardio-metabolic markers, wider physical markers, and psychosocial markers from controlled trials. The aim was to describe findings by intervention type and to stratify results by baseline BMI and level of weight loss where data allowed.
Methods
Protocol and Registration
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.
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Eligibility Criteria, Information Sources, and Search Strategy
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.
Assessment of Quality
The Critical Appraisal Skills Programme (CASP) checklist was used to assess the bias in the included studies. Studies were categorised as having a high, moderate or low risk of bias.
Data Extraction
Data was 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. Data specifically asked for included mean score change, effect size measurements (e.g., standard deviation), and stratified sample sizes.
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.
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Study characteristics were tabulated and health markers and indices, identified across the included studies, were classified into broader health categories. 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 behavioral 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 lost 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 compared to those with 6 months or greater, and then studies with less than 12 months follow up were compared to those with 12 months or greater.
Results
Study Selection
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. Eight hundred and ninety-one 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 of 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.
Study Description
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.
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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).
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).
Benefits of Modest Weight Loss
Improvements in Health Markers
The review of 70 studies revealed that even a weight loss of less than 5% can lead to improvements in various health markers. Overall, 60% of the studies reported improvements in health, while 37% showed mixed results or no change. Only 3% observed a worsening of health markers or indices. It's important to note that even non-significant improvements were classified as improvements, acknowledging that small reductions in body weight can still have positive effects on health outcomes.
Specific Health Categories Affected
The health markers and indices were categorized into 11 different health categories. The most frequently reported categories were metabolic markers, cardiovascular markers, and anthropometric measures. This suggests that modest weight loss can have a beneficial impact on these key areas of health.
Impact on Various Health Conditions
Individuals with excess weight are at an increased risk for various diseases and chronic health conditions including cardiovascular diseases, type 2 diabetes, some types of cancer, anxiety and depression. 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.
The Role of Lifestyle Interventions
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.
Risks and Considerations
Potential Side Effects of Weight Loss Medications
Anti-obesity medications help many patients lose weight and keep it off. Medication can be part of a comprehensive obesity treatment plan. Research has begun to analyze side effects, particularly for GLP-1 agonists like semaglutide. For example, a paper published in late 2023 in JAMA quantified gastrointestinal adverse events ranging from nausea to pancreatitis. Because stopping one of these medications comes with a high risk of weight regain, a person taking them should understand the risks. If a patient is hesitant to try a certain medication due to concerns about side effects, you may wish to prescribe an alternative. There are many options available that target different mechanisms of hunger, fullness, and weight loss. As medications are on the market longer, knowledge of their side effects increases. A 2023 analysis found that 68% of people taking semaglutide or liraglutide for weight loss stopped within a year. That population may have stopped for a variety of reasons, including side effects, cost coupled with lack of insurance coverage, or simply shortages of the medications. In the study above, 4.5% of users stopped the drugs due to side effects. The side effects that many people cite as their reason for quitting are digestive ones, including nausea, vomiting, and upset stomach.
Specific Medications and Their Side Effects
- Phentermine: Side effects include headache, overstimulation, high blood pressure, insomnia, rapid or irregular heart rate, and tremor.
- Phentermine-Topiramate: Side effects include abnormal sensations, dizziness, altered taste, insomnia, constipation, and dry mouth. Contraindications include uncontrolled hypertension and coronary artery disease, hyperthyroidism, glaucoma, and sensitivity to stimulants.
- Naltrexone-Bupropion: The most common side effects include nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea.
- Liraglutide and Semaglutide: Gastrointestinal issues are the most common complaint among people who are just starting semaglutide. Headlines have warned of increased suicidal ideation associated with semaglutide. Researchers concluded that the use of the GLP-1 agonists was associated with an increased risk of pancreatitis, bowel obstruction, and gastroparesis.
- Orlistat: Works by blocking the enzyme that breaks down fats consumed through food, thereby inhibiting the absorption of dietary fats. The undigested fat is then passed through the body.
- Tirzepatide: Common side effects include constipation, upset stomach, bloating, and diarrhea. Potential serious side effects also include stomach problems, kidney problems or failure, gallbladder problems, pancreatitis, or hypoglycemia, among others.
Long-Term Considerations
VCU Health expert says new weight loss medications on the market are long-term drugs. That means for the best results, patients have to be on them the rest of their lives. People can't go on the drugs for a short amount of time, lose weight, and then promptly stop taking the medication. These drugs are long-term drugs, meaning you may have to be on them the rest of your life. “When you stop the meds, you can rapidly regain weight,” Wolver said.
Eligibility and Cost
Eligibility for weight loss medications is typically based on body mass index (BMI). For semaglutide or liraglutide, a patient must must be an adult or child age 12 or more, with a BMI of 30 or greater or with a BMI of 27 or greater with comorbidities such as high blood pressure, diabetes, or high cholesterol. People who have a BMI of 30 or above do not need to have a chronic disease associated with their BMI, because obesity is considered a chronic disease. Requirements are similar for many other weight loss medications, including phentermine, naltrexone-bupropion, and orlistat, although not all are FDA-approved for use in children. The more recently approved tirzepatide is approved only for adults with a BMI of 30 or greater.
Also, the drugs are not covered by many insurances including Medicare and the cost is $1,300 a month if you are paying out of pocket. However, Wegovy and Zepbound now recently have cash pay options which are about half the retail price.
The Importance of Lifestyle Modification
When Wolver works with patients, she performs an extensive evaluation of all the factors that may contribute to their weight issues. “People usually don't come to me with normal BMI's. I treat the disease of obesity,” she said. “Our main goal is to get people healthy and not necessarily to lose weight. We use lifestyle modification which includes teaching them how to eat a nourishing diet, along with exercising and behavior modification. We talk about their sleeping habits and managing their mental health,” she said. “If they are eligible, we discuss medications or surgery.”
Addressing the Root Causes of Weight Issues
Most of the patients who have obesity tell Wolver that they have tried everything they can to lose weight. “Oftentimes, they have been told by their providers to eat less and move more. Although exercise is critically important to good health, especially as you age, it doesn't help much with weight loss,” Wolver said. “We try to look for root causes and help them with that, whether that be challenges with understanding a healthy diet, being able to implement it, barriers to exercise, mental health issues or disordered eating.