Beyond the Scale: Weight Loss Quality Takes Center Stage in Modern Obesity Management
A new focus on restoring health, not just reducing pounds, is reshaping the approach to obesity treatment, with clinicians prioritizing the quality of weight loss alongside the quantity.
The landscape of weight loss is undergoing a significant shift. A recent industry-sponsored review reveals that emerging treatment options are enabling healthcare professionals to move beyond simply measuring weight loss and instead concentrate on improving the overall health status of patients with obesity.
“Weight loss quality is a new concept,” explained a lead researcher in Diabetes, Obesity, and Metabolism. “The discussion no longer revolves around the lack of adequate efficacy but rather around how can the health status of the patient with obesity be restored to a normal and healthy state.”
Individuals are achieving substantial weight loss through methods like bariatric surgery and newer anti-obesity medications – including semaglutide and tirzepatide – with even more innovative drugs currently under investigation. While weight loss is known to reduce the risk of conditions like diabetes, liver disease, and cardiovascular complications, and improve osteoarthritis, it can also lead to the loss of vital lean and bone mass, particularly in older adults and those with frailty.
The Evolving Treatment Landscape
Recognizing these complexities, researchers reviewed current treatment options and proposed targets for assessing weight-loss quality.
Diet & Exercise: Traditional approaches like diet and exercise remain foundational, offering low cost and minimal adverse effects. However, adherence is often a challenge. Very low-calorie diets, while effective for rapid initial weight loss, can also contribute to lean and bone mass loss. Diets such as ketogenic, low-fat, and Mediterranean have demonstrated consistent results, while intermittent fasting and time-restricted eating are areas of ongoing study.
Bariatric Surgery: Currently the most effective intervention, bariatric surgery can lead to 30%-35% weight loss and often normalizes a patient’s weight. Benefits extend to diabetes remission, improvements in cardiovascular health and metabolism-associated steatohepatitis (MASH), and relief from osteoarthritis pain. However, it is an invasive procedure with potential for nutritional deficiencies.
Classic Medications: First- and second-generation anti-obesity medications, including orlistat, naltrexone-buproprione, and phentermine-topiramate, offer modest weight loss but are often associated with adverse events.
Incretin-Based Therapies: The glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide has shown promise, inducing up to 15%-17% weight loss through appetite suppression and altered food preferences. It also offers cardiovascular benefits, though its impact on bone health remains unclear.
Tirzepatide, a dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, approved for both type 2 diabetes (Mounjaro) and obesity (Zepbound), has demonstrated even more significant results, with patients experiencing up to 20% placebo-corrected weight loss and a positive impact on lean mass. Several new drug candidates are in development, including oral GLP-1 agonists like oral semaglutide and orforglipron, as well as long-acting injectable dual/triple receptor agonists such as survodutide and pemvidutide. These newer agents aim to target both appetite regulation and fat oxidation in the liver. Early data suggests the investigational triple-receptor agonist retatrutide may offer even greater weight loss potential than tirzepatide.
LAARAs & DACRAs: Research is also exploring peptides with amylin receptor agonism, categorized as long-acting selective amylin receptor agonists (LAARAs) and dual amylin and calcitonin receptor agonists (DACRAs). The investigational drug cagrilintide has reportedly induced 8-10% weight loss.
Multi-receptor agonists: Studies suggest combining incretins and amylin-receptor agonists could further enhance outcomes.
Defining Weight Loss Quality
The focus on quality extends beyond simply achieving a lower number on the scale. Key targets include:
Reduce Fat Mass: While subcutaneous fat is considered relatively benign, abdominal fat – including perivascular, epicardial, perirenal, and epididymal adipose tissues – is linked to insulin resistance, hypertension, and other complications. The goal is to redistribute fat storage to healthier depots.
Protect Lean Mass: Loss of lean mass, encompassing skeletal muscle, the heart, kidneys, and liver, can lead to reduced strength, energy expenditure, and insulin sensitivity. Loss of lean mass is a predictor of poor cardiovascular outcomes, highlighting the importance of exercise in maintaining weight stability after loss.
Improve Insulin Sensitivity: Restoring insulin sensitivity is crucial, as its loss is a primary driver of type 2 diabetes and related cardiovascular issues.
Improve Liver Function: Obesity significantly impacts liver health, often leading to metabolic fatty liver disease (MAFLD) or metabolism-associated steatohepatitis (MASH). Weight loss is essential for improving liver steatosis, and early treatment of MASH is vital.
Improve Heart Health: Cardiovascular disease, a major complication of obesity, impacts physical function and contributes to muscle deterioration. A holistic approach addressing both fat reduction and insulin sensitivity is needed, particularly in cases of heart failure with preserved ejection fraction (HFpEF).
Prevent Bone Loss: While obesity and type 2 diabetes can increase bone mass, they often compromise bone strength due to factors like muscle dysfunction, insulin resistance, and inflammation. This increases the risk of fragility and falls, especially in women. Notably, anti-obesity medications do not appear to harm bone health and may even improve it.
Reduce Joint Pain: Osteoarthritis, a common source of pain and disability in older adults, is often exacerbated by excess weight. Potent anti-obesity medications, including incretins and novel candidates derived from salmon calcitonin, show promise in alleviating joint pain, even independently of weight loss.
Improve Quality of Life: Bariatric surgery can significantly improve health-related quality of life, but its invasive nature and potential for lean and bone mass loss necessitate careful consideration. Medications can also have side effects, such as nausea and vomiting; up to 7% of individuals taking semaglutide discontinue use due to gastrointestinal issues.
Sustain Weight Loss & Durability: Lower metabolic rates and increased hunger hormones often contribute to relapse. A personalized approach combining diet, exercise, pharmacotherapy, and surgery, with a focus on protecting lean mass and promoting satiety, is essential for long-term success.
Ultimately, experts emphasize the importance of addressing the rapid weight regain that often occurs after treatment cessation. “One aspect that needs careful addressing is the rapid return to the pre-intervention weight status upon the cessation of treatment,” noted a researcher. “While the newest drug candidates seem to be able to control body weight during the intervention, they all lose the effect shortly after the cessation of treatment.” The researchers concluded that “the greatest success in terms of weight loss maintenance comes from exercise.”
