Sarcopenia unlikely for most after weight loss, but more data needed on older adults
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Key takeaways:
- Adults who lose a substantial amount of weight with obesity treatment lose more fat mass than fat-free mass.
- Declines in fat-free mass from GLP-1 therapy may adversely affect some older adults.
Most adults who lose weight as part of obesity therapy should not experience sarcopenia due to a decrease in fat-free mass, but more research is needed on the impact of GLP-1 receptor agonists and similar drugs on older adults.
A debate held at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease centered on the potential risk for sarcopenia among adults who achieve a large weight loss, particularly those who undergo bariatric surgery or lose weight while using obesity medications. Samuel Klein, MD, chief of the division of nutritional science and obesity medicine and the William H. Danforth Professor of Medicine and Nutritional Science at Washington University School of Medicine in St. Louis, discussed how adults with obesity who lose weight improve their physical function and muscle quality.
“Weight loss-induced relative reduction in fat-free mass, or skeletal muscle mass, is less than the relative reduction in fat mass,” Klein said during a presentation. “The ratio of fat-free mass, or skeletal muscle mass, to body weight is always increased.”
Richard E. Pratley, MD, the Samuel E. Crockett Chair in Diabetes Research and medical director of AdventHealth Diabetes Institute and a Healio | Endocrine Today Co-editor, acknowledged that while a reduction in fat-free mass during weight loss does not affect physical function for most people, more studies of older adults are needed to account for that population’s decrease in muscle mass as part of the aging process.
“One of my concerns is that we are accelerating this loss of muscle mass with GLP-1 treatments and that we’re actually increasing this rate of muscle mass loss in older individuals,” Pratley said.
Weight loss benefits physical function
Previous research has shown the percentage of weight loss from fat-free mass among adults who lose a large amount of body weight varies greatly. In a meta-analysis of studies assessing weight loss after bariatric surgery, adults lost between 19% and 35% of their body weight at 1 year. The percentage of weight loss from fat-free mass ranged from 12% to 44%.
Klein noted women tend to lose less fat-free mass than men with the same amount of weight loss, as they typically have less mass to begin with. Similarly, older adults lose less fat-free mass than younger people with the same amount of weight loss.
“This is really a function of body composition that actually determines, to some extent, the composition of the weight you lose,” Klein said.
Findings published in Obesity revealed that the percentage decline in body fat mass with weight loss is greater than the decrease in overall body weight. Researchers examined weight reductions in the CALERIE phase 2 trial, with bariatric surgery, with semaglutide 2.4 mg (Wegovy, Novo Nordisk) and with tirzepatide 10 mg (Zepbound, Eli Lilly). With all four therapies, the percentage of body fat mass lost was approximately double the percentage loss of body weight.
Another study published in Obesity Surgery in 2020 found adults who lost 33% of their total body weight 3 years after bariatric surgery had a 55% decline in fat mass and a 15% decrease in fat-free mass.
“You always lose a greater percent of your fat mass than your fat-free mass,” Klein said. “This means these ratios are beneficial.”
Klein noted weight loss may also improve muscle quality by improving the body’s ability to deliver blood to muscle tissue, changing the muscle’s composition to decrease the amount of fat in it, and improving insulin sensitivity in the muscles.
Losing a large amount of weight may also improve muscle strength. Data published in The Journal of Clinical Endocrinology & Metabolism in 2019 found adults who lost 30% or more of their body weight 1 year after undergoing bariatric surgery had a decrease in absolute grip strength. However, absolute grip strength in relationship to change in BMI and appendicular lean mass increased, and participants had increases in gait speed and declines in chair stand time and 400 m walk time.
Klein acknowledged some health care professionals expressed concerns that GLP-1 therapy may lead to large loss of fat-free mass, but he said data that have been published so far have found the percentage of fat-free mass lost with GLP-1 therapy is similar to what previous research has found with weight loss after bariatric surgery.
“The concern that marked weight loss induced by GLP-1-based therapy can cause physical frailty and sarcopenia is not supported by any data,” Klein said.
Sarcopenia and older adults
Pratley agreed with most of Klein’s points regarding the loss of fat-free mass when a person loses a substantial percentage of body weight, but added there may need to be special considerations for older adults, especially those prescribed GLP-1 receptor agonists.
Pratley discussed how adults experience a decline in lean body mass and functional capacity as they age. Some adults are on an “accelerated aging” pathway where the decline in muscle mass is experienced at a younger age due to comorbidities. The loss of lean body mass can occur following several events such as a fall, an injury or hospitalization.
“We might need to be more careful with weight loss [for older adults],” Pratley said. “We have to balance the weight loss and all of those positive benefits against decreases in function, increases in falls and decreases in bone mineral density and bone health.”
According to a narrative review published in Diabetes Care in 2024, adults who lost weight with GLP-1 receptor agonist therapy had a 6 kg reduction in lean mass and a 17 kg decrease in fat mass. Pratley said while the decrease in fat mass was greater than the lean mass loss, the loss of lean mass was equivalent to a decade’s worth of lean mass that a person typically loses due to aging.
Pratley also cautioned against extrapolating clinical trial data regarding fat-free mass decreases to older populations.
“Clinical trial populations are not the same as clinical populations,” Pratley said. “In clinical trials, they are oftentimes younger, more functional because they have to come into the clinic, and they oftentimes have fewer comorbidities. In our [real-world] clinics, they are often older, frail, more likely to have multiple comorbidities and sometimes have unknown nutritional status.”
To combat fat-free mass and muscle loss, Pratley said physicians should encourage older adults to exercise. In the narrative review published in Diabetes Care, researchers cited data where adults who used liraglutide (Saxenda, Novo Nordisk) and participated in exercise were able to increase their lean mass by 0.5 kg at 1 year, even though they had a 3.4 kg decline in body mass and 4.7 kg decrease in fat mass.
Pratley noted there are several medications in the pipeline that are targeted at the myostatin pathways and are designed to reduce body weight for a person with obesity while preserving lean mass. One of these medications is bimagrumab (Eli Lilly), which induced reductions in body weight and HbA1c in a phase 2 trial. Participants receiving the study drug had a 20.5% reduction in fat mass and a 3.6% increase in lean mass at 48 weeks.
“There’s a lot of activity in this field that might be useful, particularly for our older individuals who are at risk for the loss of lean body mass,” Pratley said.
References:
Alba DL, et al. J Clin Endocrinol Metab. 2019;doi:10.1210/jc.2018-00952.
Hall KD. Obesity. 2024;doi:10.1002/oby.24027.
Heymsfield SB, et al. JAMA Netw Open. 2021;doi:10.1001/jamanetworkopen.2020.33457.
Locatelli JC, et al. Diabetes Care. 2024;doi:10.2337/dci23-0100.
Nuijten MAH, et al. Obes Surg. 2020;doi:10.1007/s11695-020-04654-6.
Sylivris A, et al. Obes Rev. 2022;doi:10.1111/obr.13442.
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Klein S, et al. Session 10: Sarcopenia association with obesity – myth and reality. Presented at: World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease; Dec. 12-14, 2024; Los Angeles.
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