Dosage determines how well a drug works, and for many important prescription drugs, dosage is determined by a patient’s weight. Usually, this isn’t a problem: changes in weight enough to significantly affect dosage often happen gradually enough for a doctor to notice and adjust the prescription. But in the era of new weight-loss drugs, that may no longer be the case.
in A cautionary tale published Monday in the journal JAMA Internal MedicineResearchers at the University of Colorado reported the case of a man who had lost about 30% of his body weight over a six-month period using a new weight-loss drug. He then visited the emergency department complaining of palpitations, excessive sweating, confusion, fever, and trembling hands. Atrial fibrillationCardiac arrhythmias are irregular heartbeats that can lead to heart failure or stroke if left untreated.
The 62-year-old man had no history of atrial fibrillation, but had been diagnosed with obesity, type 1 diabetes, and hypothyroidism (a condition in which the thyroid gland does not produce enough thyroid hormone) for which he was taking levothyroxine, a synthetic thyroid hormone dosed according to weight.
Six months before his visit to the emergency department, the doctor had written the man a prescription. Tirzepatide (Zepbound)It is a dual agonist of gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) used for chronic weight management. The plan was to start with 2.5 milligrams of tirzepatide and increase the dose every 4 weeks to reach 10 mg, but the man reached 10 mg in 4 months and continued taking it for 2 months after that. The man was scheduled for a follow-up appointment to evaluate his progress, but missed it.
When he started taking tirzepatide, the man weighed 132 kg (291 lb) and was taking 200 micrograms of levothyroxine per day (about 1.5 micrograms/kg). Six months later, the man’s weight was 93 kg (205 lb), but he was still taking 200 micrograms of levothyroxine, which had increased to 2.15 micrograms/kg.
Dangerous amount
The emergency department physicians performed blood tests on the man’s TSH (also called thyroid-stimulating hormone or thyrotropin). TSH is inversely related to thyroid hormone levels; low TSH means too much thyroid hormone, and high TSH means too little. In nonpregnant adults, the normal level of TSH in the blood is about 0.5 to 5.0 mIU/L. The man’s TSH had fallen from 1.9 mIU/L before starting tirzepatide to 0.001 mIU/L by the time he arrived at the emergency department, indicating too much thyroid hormone.
The doctor told the man,Thyrotoxicosis In the context of rapid weight loss due to tirazepam, this diagnosis explained his symptoms well. Low TSH levels increase risk of atrial fibrillation three-fold.
The Colorado researchers offered this case as a cautionary tale: In the era of weight-loss drugs, doctors should evaluate their patients’ other prescribed medications to see whether they need to be adjusted to account for major changes in weight, the researchers said. Many types of medications rely on weight-based dosing, including insulin, anticoagulants, anticonvulsants, antibiotics and antifungals, the researchers noted.
in Accompanying editorialA group of researchers led by Professor Tyrone Johnson of the University of California, San Francisco, called for “greater vigilance” as the man’s illness could have been prevented, and discussed the case in the context of the current market for new weight-loss drugs, which have high out-of-pocket costs and are in short supply.
These factors may drive some patients to the direct-to-consumer market, compounding pharmacies, and counterfeit products, all of which involve, to say the least, “suboptimal prescribing” and inadequate clinical oversight. This case “highlights the potential dangers of poor prescribing of GLP-1/GIP receptor agonists and supports the need for strong patient-clinician partnerships during use,” the researchers wrote.
