With the use of a new drug, over time, information about adverse effects becomes clearer. Late effects of a medication may not be known until it has been in use for years. Clinical trials may last for 7-10 years, and still adverse effects may not be known until later. It’s like with measles vaccine immunity. We thought it was permanent until measles outbreaks occurred in people vaccinated previously.
The same has occurred with Glucagon-Like Peptide-1 Receptor Agonists, aka GLP-1’s. They are so popular and have been prescribed so much that patients are beginning to experience unanticipated adverse effects. Elderly patients, whose physical makeup is undergoing significant aging changes already, are far more susceptible to these adverse events than young or middle aged adults. Prescribers are beginning to see these occurrences and are concerned they may be more of a problem than was originally thought.
These effects have been categorized as either high risk or moderate risk based upon the degree and duration of harm they cause. High risk effects are obviously longer term and potentially more harmful. What follows is an explanation of those events and what to look for when they are occurring.
HIGH RISK ADVERSE EFFECTS:
SARCOPENIA—the age-related loss of skeletal muscle mass and strength. One’s muscles deteriorate, atrophy (shrink), and weaken. Patients experience frailty, falls, disability, and functional decline. GLP-1’s accelerate that functional decline. Weight loss plus sarcopenia
make weakness and falls more likely
BONE LOSS—osteoporosis, which occurs in the elderly and sedentary, is worsened by GLP-1’s putting them at 12% increased risk for fractures. Weight loss plus bone loss reduces the forces that stimulate new bone formation. Sedentary bones lose Ca++.
DEHYDRATION/ACUTE KIDNEY INJURY—a largely reversible event caused by nausea, vomiting, diarrhea, and reduced fluid intake. These events put an elderly patient at high risk for dehydration and electrolyte (sodium and potassium) abnormalities. These can cause seizures and heart rhythm problems. If dehydration goes on long enough, damage to kidney function can occur.
MODERATE RISK ADVERSE EFFECTS:
GI SIDE EFFECTS—any drug can cause nausea, diarrhea, abdominal pain, and vomiting. In the elderly, these effects have greater consequences and should not be ignored.
HYPOGLYCEMIA—an obvious adverse effect of a diabetes drug that is intended to lower blood sugar. It is easily reversible, but requires adjustment of the GLP-1 dosage.
NEUROLOGIC CHANGES—dizziness is the primary neurologic event.
Counteracting these events requires the physician to “keep an eye on” his patient. The elderly require closer monitoring of hydration and electrolyte status. Check a patient’s labs often—Na, K, Cl, CO2, kidney function.
Improve one’s diet (60-90 GM protein per day) and drink 64 oz of fluid/day. Maintain muscle strength and prevent bone loss by exercise to include Resistance training. GLP-1’s should be started at a low dose taken once a week and increased every 4 weeks.
RELATIVE CONTRAINDICATIONS FOR GLP-1’s—dementia, stage 4 Chronic Kidney Disease, sarcopenia or osteoporosis at baseline, psychiatric illness, anorexia, depression.
I’ve gotten a bit carried away with this article. It is more detailed than is probably needed, but the purpose is to tell older patients to use GLP-1 drugs with caution, not haphazardly, and not without monitoring potential problems. In order to lose weight, the drug is affecting your metabolism in a negative way. It’s like it’s eating away your fat, but it’s also eating your bones and muscles. Reductions in “lean body mass” (muscle, bone, organs, water) account for 12%-40% of total weight loss. All drugs are poisons if taken wrong or in excess, and GLP-1’s are no exception.
Reference: Lamberg E, Older Patients Have Specific Risks for GLP-1 Use Medscape 2026 February 3.
Misra M. Do GLP-1’s Have Deleterious Effects on Muscle? Medscape 2026 January 27.
