As next generation antiobesity medications (AOMs) take the culture by storm, many providers and researchers are asking an important question: how are distinct subsets of the population differently impacted by these drugs? The answers to this question may help dietitians better understand which patients may be more susceptible, for example, to gastrointestinal side effects and other nutrition-related concerns.
There are relatively larger gaps in the research concerning the effects of AOMs on older adults, aged 65 and up. One recent systematic review, published in late 2025 in Obesity (Silver Spring), compiled data from experimental studies (five secondary analyses of randomized clinical trial data and one single-arm trial) and two observational studies with participants all older than 65 years. Experimental studies included patients with obesity and prediabetes or CVD. All studies found statistically significant weight reduction between intervention and placebo groups or compared with baseline weight. However, authors—including first author, Yale School of Medicine’s Alissa Chen, MD, MPH—note that older adults had a higher prevalence of gastrointestinal adverse events when taking AOMs. Another finding was that people discontinued taking the medication more often.1
In an interview with Chen, she emphasized that older adults may be prone to adverse events that may interact with other medications they take, which could result in a severe downstream effect. For example, “There is a potential increased risk of falls among older adults taking glucagonlike peptide-1 receptor agonists (GLP-1s) due to dehydration,” she says.2
As the study outlines, aging-related changes in the autonomic nervous system, use of other medications, and arterial stiffness put older adults at risk for orthostatic hypotension. Decreased oral intake from gastrointestinal side effects of semaglutide and tirzepatide may exacerbate this, leading to orthostatic hypotension and falls.1
Kasia Lipska, MD, MHS, BS, and senior author of the study points out that obesity in older adults “deserves its own science rather than being treated as a simple extension of midlife obesity.” The effects of aging on metabolism, including those related to muscle and bone mass, pain and inflammation, mobility, and overall functional capacity, may alter how older individuals respond to AOMs. 2
Which AOMs, Exactly?
It’s important to note that AOMs used in the studies included in the systematic review included all AOMs currently approved by the FDA for chronic and short-term treatment: orlistat, phentermine-topiramate, naltrexone-bupropion, liraglutide, subcutaneous semaglutide, tirzepatide, phentermine, benzphentamine, diethylpropion, and phendimetrazine.1 This means that effects were assessed from not only so-called next-generation AOMs (like GLP-1s semaglutide and tirzepatide) but also first-generation drugs with widely varying mechanisms of action. For example, phentermine and diethylpropion are sympathomimetics that suppress appetite by stimulating norepinephrine release and thus reducing hunger; topiramate is an antiepileptic used off-label for weight loss, exerting an anorexigenic effect through modulation of gamma-aminobutyric acid receptors in the brain; bupropion is a dopamine and norepinephrine reuptake inhibitor, promoting weight loss by increasing the activity of pro-opiomelanocortin neurons in the hypothalamus and reducing appetite; and orlistat is a lipase inhibitor that reduces the absorption of fat from food.3
Given the diversity of drug types, mechanism of action, and potential downstream physiological effects of each of these drugs, authors are casting a very wide net in their assessment of side effects and risks in older adults. Future studies are needed to not only explore the broad topic concerning AOM use in older adults, but the narrower paths of inquiry related to important differences in drug type, dose, and duration. Some of the first-generation AOMs have stricter guidelines for duration of use (eg, phentermine use is FDA-approved for only three months) when compared with GLP-1s. While off-label use takes place with several AOMs, not all questions concerning risks of longer-term use have been answered.
Searching for Clarity
In effort to address this gap in the research related to how AOMs affect older adults in the real world, Chen is leading two studies on veterans aged 65 and older using GLP-1 medications. The purpose of the first study is to understand how GLP-1 agonists help individuals meet their goals—primarily related to function and quality of life. Chen will interview participants at the VA Connecticut Healthcare System before they begin the medication to collect information about their quality of life, including physical function, mood, pain, and expectations for the trial. The participants will then be surveyed again six months after starting the drug so researchers can learn about their experience.2
In the second study, Chen will use national VA data to investigate the weight loss effect of GLP-1 agonists in older adults. Because real-world weight loss often differs from weight loss in a clinical trial, the study will provide better insight into what to expect when not in a controlled environment, she says.
Weight Loss-Focused Interventions in Older Adults
As we age, natural changes in body composition result from multiple biological and sociological factors. Lean mass typically begins declining in our 40s, resulting in part from declines in serum testosterone and other hormones, increased leptin resistance, and reduced responsiveness to thyroid hormone. Reduced mitochondrial volume and oxidative capacity also contribute to declines in resting metabolic rate that may further increase body fat. Older adults are also at risk of developing anabolic resistance due to reduced amino acid availability, muscle perfusion and uptake, and digestive capacity. There is a natural tendency for weight redistribution centrally, loss of height, and increased kyphosis (excessive forward curvature of the spine) due to age-related changes in bone metabolism. As a result, BMI may be a less helpful indicator.4
In older adults, obesity is associated with worsening physical function, impaired quality of life, nursing home placement, and reduced life expectancy. It is also associated with cardiometabolic disorders, obstructive sleep apnea, osteoarthritis, cancer, and cognitive dysfunction. However, addressing these concerns in older adults contains an added layer of complexity. Weight loss may paradoxically exacerbate frailty or disability. An increasingly recognized subgroup of older adults with obesity has coexistent sarcopenia, which places them at an exaggerated and higher risk of functional decline and adverse events.4
There is ongoing debate about weight loss interventions in older adults with obesity. However, research suggests that the lowest risk approaches may include ones that contain the following elements4,5:
- avoidance of rapid weight change;
- conservative caloric restriction while meeting protein needs;
- aiming for protein intake of at least 1 to 1.2 g/kg/day for healthy, aging populations, and intakes of 1.2 to 1.5 g/kg/day may be necessary for those with chronic or acute conditions. Needs may increase to 2 g/kg/day in more severe cases of illness, malnutrition, and chronic conditions;
- evenly balanced protein distributions of 25 to 30 g of dietary protein (0.4 g/kg) per meal from animal and plant protein sources alike are helpful to maximize muscle protein synthesis rates in older populations; and
- personalized exercise programs that focus on regular aerobic, resistance, and stretching activities. Strength-focused exercise may be particularly helpful.
Caloric restriction alone was found to be more likely to result in sarcopenia, increased frailty, and loss of bone mineral density. Incorporating adequate protein and physical activity (tailored to personal needs) is highly important for helping to preserve lean muscle and bone mass, strength, and function in older adults.4
Tying It Together
Dietitians and other providers can educate older adult patients and clients interested in taking AOMs about the gaps in current research, the potential for increased risk of adverse effects, and the importance of managing risks through foundational diet and lifestyle approaches (including physical activity) that ensure muscle and bone mass, strength, and functional capacity are preserved. While these recommendations are appropriate for anyone taking AOMs, the heightened risks in older adults warrants even greater vigilance.
— Heather Davis, MS, RDN, LDN, is editor of Today’s Dietitian.
References
1. Chen AS, Hajduk AM, Grimshaw AA, Fried TR, Jastreboff AM, Lipska KJ. Efficacy of antiobesity medications for weight reduction in older adults: a systematic review. Obesity (Silver Spring). 2025;33 Suppl 1(Suppl 1):11-21.
2. Anderson A. What is the impact of GLP-1s in older adults with obesity? Yale School of Medicine website. https://medicine.yale.edu/news-article/what-is-the-impact-of-glp-1s-in-older-adults-with-obesity/. Published January 5, 2026. Accessed April 4, 2026.
3. Ziyadeh F, Saliba S, Bacha DS, Mauer Y, Griebeler ML, Burguera B. Update on antiobesity pharmacotherapy in adults: current and emerging options. Cleve Clin J Med. 2026;93(1):36-46.
4. DiMilia PR, Mittman AC, Batsis JA. Benefit-to-risk balance of weight loss interventions in older adults with obesity. Curr Diab Rep. 2019;19(11):114.
5. Harris S, DePalma J, Barkoukis H. Protein and aging: practicalities and practice. Nutrients. 2025;17(15):2461.