GLP-1s Could Help Older Adults With Frailty

For adults with obesity, weight loss from GLP-1 medications can yield numerous health benefits. But experts worry that weight loss that happens too rapidly can increase the likelihood of muscle loss — a risk that may be especially relevant for older adults with frailty who are already experiencing strength and mobility issues.

The analysis challenges conventional thinking around GLP-1 use in this group. “There are persistent concerns around the balance of risk and benefit with GLP-1 receptor agonist–based medications, such as semaglutide, in this population,” says the lead study author, John W. Ostrominski, MD, MPH, an obesity medicine specialist at Brigham and Women’s Hospital and Harvard Medical School in Boston.

As a result, some healthcare providers are hesitant to prescribe GLP-1s for older adults. “Frailty is something we absolutely need to consider when we’re treating older adults,” says Kelley Gregorovic, RN, a nurse practitioner at Tufts Medicine’s Weight and Wellness Center at Melrose Wakefield Hospital in Stoneham, Massachusetts. “But I don’t want frailty alone to become a reason that patients can’t access these medications, particularly when we know the benefits can extend well beyond weight loss.”

Semaglutide Improved Heart Health and Quality of Life Even Among the Most Frail Adults

The new research, published in JAMA Cardiology, is a secondary analysis of a randomized clinical trial, meaning it reexamined existing data to address a new question.

The study included data from more than 17,000 older adults diagnosed with heart disease and overweight or obesity. Participants received either Wegovy or a placebo (sham drug) once a week for two years. Researchers also assessed each participant on a frailty index, based on a number of age-related health issues.

At the end of two years, adults taking semaglutide had a lower risk of heart attack, stroke, and heart disease-related death than their peers who got the placebo — regardless of their frailty index score. Semaglutide also reduced the risk of heart failure, hospitalization, and death from any cause, and improved self-reported quality of life.

Significantly, these benefits were strongest among adults with the highest levels of frailty, compared with those who took a placebo. Participants were also less likely to stop taking semaglutide compared with a placebo when they had a higher baseline frailty score.

Excess Weight Can Make Frailty Worse

The study was funded by Novo Nordisk, the maker of the semaglutide drugs Ozempic and Wegovy, and several of the study’s researchers reported compensation from Novo. Still, healthcare providers say the findings make sense.

Much of the benefit comes from fat loss, according to Mir Ali, MD, the medical director of the MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, California, who was not involved with the research. “The benefits of weight loss often outweigh the possible loss of muscle,” he says. “Frailty can actually improve with weight loss in people with overweight or obesity.”

Excess weight causes chronic inflammation in the body that may exacerbate underlying health conditions. Extra pounds can also place more stress on joints that can limit mobility, Dr. Ali says. “Losing weight may combat those factors,” he says.

Gregorovic says the heart benefits of a GLP-1 can also work against frailty, raising a person’s mobility and quality of life. “It’s really interesting that measures of frailty moved in a favorable direction with semaglutide, while they worsened over time with placebo,” she says, calling the findings “very reassuring” for older adults with obesity and overweight.

She also points out that many older adults already come to healthcare providers with some degree of age-related muscle and bone loss before they start an obesity medication, Gregorovic says. “We’re starting from a different place than we might be with a younger patient, and that needs to be part of the conversation,” she says.

Previous Research on GLP-1 Use Among Older Adults Has Shown Mixed Results

Loss of ‘Lean Mass’ Isn’t Synonymous With Muscle Loss

“The concern is real,” when it comes to GLP-1 use among adults with frailty, “but I think it sometimes gets oversimplified,” Gregorovic says.

“Anytime someone loses a significant amount of weight, we’re going to see some loss of lean mass along with fat mass,” she continues. “But lean mass and muscle aren’t interchangeable.” Lean mass includes muscle, but also water, glycogen (energy stored in the body), organs, connective tissue, and other nonfat tissue. “So, when we hear that a certain percentage of weight loss was lean mass, we shouldn’t assume that someone lost that same percentage of their muscle,” Gregorovic says.

Steps to minimize muscle loss still need to be taken, she says. But muscle loss is to be expected at this stage of life. “Some degree of muscle and bone loss is already happening as we age, and some older patients may already be starting with less muscle, strength, or mobility,” Gregorovic says.

It’s Important to Look at Each Patient as an Individual, Experts Say

“Use of GLP-1 receptor agonist-based therapies should always be individualized, used in combination with optimal health behaviors, and closely monitored in collaboration with a health professional,” Dr. Ostrominski says.

Gregorovic says that healthcare providers shouldn’t avoid treating obesity because of frailty concerns. “It means we need to be more thoughtful about how we do it,” she says. That can mean slowly ramping up the dosage of semaglutide, if needed. “I’m looking for the therapeutic dose that gives us the benefit we’re looking for while still allowing that person to eat well, stay hydrated, be active, and feel well,” she says.

Overall, Ostrominski recommends that older adults who are considering GLP-1 medications talk to their healthcare provider about their individual risks and benefits. If the decision is made to move forward with the medications, doing regular aerobic and resistance training, along with slowly and gradually increasing the dosage, can be helpful to combat frailty, he says.