Image: Adobe Stock<\/em>
\u201cAccording to the researchers, emerging and increasingly used obesity medications such as GLP-1 receptor agonists \u201cinduce unprecedented weight loss of 15% to 20%. These agents hold great promise for improving long-term health and revolutionizing the treatment of obesity as a chronic disease.\u201d<\/p>\n
\u201cHowever, concerns have emerged about potential adverse effects of incretin-based therapies related to [fat-free mass (FFM)] loss, which includes muscle, bone, organs, connective tissue and total body water, and its potential consequences for musculoskeletal function,\u201d they wrote.<\/p>\n
In the systematic review, also presented at the ACP Internal Medicine Meeting, Batsis and colleagues assessed 36 randomized controlled trials (median, 71 participants) reporting on body composition outcomes among adults aged 18 years or older who used semaglutide (Ozempic\/Wegovy, Novo Nordisk), tirzepatide (Zepbound, Eli Lilly), dulaglutide (Trulicity, Eli Lilly) or liraglutide (Victoza\/Saxenda, Novo Nordisk).<\/p>\n
In the studies, several outcomes \u2014 including changes in FFM, muscle-related indices, fat mass, lean soft tissue (LST) and visceral adiposity \u2014 were measured through dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), CT or MRI.<\/p>\n
The researchers noted that prespecified benchmarks \u201cwere applied to contextualize expected muscle-related losses.\u201d They found that 41.7% of the studies were at low risk of bias and 27.8% had prespecified body composition as a primary outcome.<\/p>\n
Batsis and colleagues reported that the proportion of muscle-related losses varied widely. The median proportion of total weight loss attributable to reductions in muscle-based indices across incretin groups was 34.9% [interquartile range (IQR), 19%-48.2%], \u201cwith 68% exceeding the benchmark of about 25%.\u201d<\/p>\n
The median total weight loss was about 34.9% (IQR, 17%-46.9%) among studies using dual-energy X-ray absorptiometry or bioelectrical impedance analysis \u2014 \u201cwith 65% exceeding the 25% benchmark\u201d \u2014 and about 35.8% (IQR, 29.8%-50.4%) among studies using CT or MRI, with all exceeding the 15% benchmark.<\/p>\n
Batsis and colleagues noted that 14 of the studies that reported weight loss in a placebo or lifestyle comparator group showed a median weight loss of \u20132.4% (IQR, \u20134.4% to 1%), half of which exceeded the benchmark, \u201csuggesting that disproportional muscle loss is not a unique feature of incretin-induced weight loss.\u201d<\/p>\n
The researchers acknowledged that a challenge of interpreting the findings \u201cis the absence of a standardized framework for defining clinically meaningful muscle-related losses.\u201d<\/p>\n
\u201cPercentage-based body composition measures may be misleading because preferential fat loss can artifactually increase the relative proportion of FFM or LST even when absolute values decrease,\u201d they wrote. \u201cConversely, absolute FFM loss must be interpreted in the context of baseline body composition and total weight change.\u201d<\/p>\n
Still, the magnitude of the observed changes, \u201cparticularly in higher-efficacy weight loss trials, suggests that these changes merit careful consideration given skeletal muscle\u2019s central role in glucose disposal, metabolic regulation, energy expenditure, immune function and inflammatory homeostasis,\u201d Batsis and colleagues wrote.<\/p>\n
\u201cWe really need to be mindful of counseling our patients that this could occur and that a team-based approach is needed to manage patients with obesity using lifestyle-based therapies in addition to these medications,\u201d Batsis told Healio. \u201cThis is an exciting time for obesity medicine and these medications have transformed how we care for patients. However, as with any medication, shared decision-making is needed: the \u2018start low, go slow\u2019 approach and appropriate adjunctive therapies are critical for success. Not every patient is an ideal candidate and we need to think about individualizing care.\u201d<\/p>\n
He added that further research \u201cis needed in special populations, harmonizing body composition outcomes and ways to evaluate body composition, and to perform physical function measures.\u201d<\/p>\n
In a related editorial, Charlotte Suetta, DmSci, PhD, MD,<\/b> a clinical professor in the department of clinical medicine at the University of Copenhagen in Denmark, wrote that clinicians should understand \u201cthat some loss of muscle-related tissue is a foreseeable component of intentional weight loss, including pharmacologic weight loss.\u201d<\/p>\n
She added that treatment success \u201cshould not be defined by kilograms lost alone. This is particularly true in older adults and in patients with low muscle reserve or functional limitations.\u201d<\/p>\n
Suetta additionally wrote that the use of obesity drugs should be paired with approaches likely to preserve muscle health, \u201cespecially resistance exercise and adequate protein intake.\u201d<\/p>\n
Ultimately, \u201cthe question is no longer whether incretin-based therapies reduce body weight,\u201d she wrote. \u201cThe question now is whether we can ensure that the weight lost is predominantly fat while preserving the muscle needed for metabolic health, physical function and healthy aging.\u201d<\/p>\n
For more information:<\/h2>\n John A. Batsis, MD<\/b>, <\/b>can be reached at primarycare@healio.com.<\/p>\n\n
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