Extreme Side Effects Followed Overdose of Unapproved Weight-Loss Drug

Use of an unapproved triple-hormone receptor agonist bought online led to extreme side effects stemming from intractable diarrhea in a man who obtained the drug online from a direct-to-customer seller.

A 32-year-old man with a medical history of hypertension came to the emergency department (ED) due to diarrhea with onset over the last 7 days. The patient said that his symptoms started after giving himself a shot of retatrutide, which he’d purchased online for weight loss, reported Opeyemi Komolafe, MD, of the Medical University of South Carolina in Florence, in Annals of Internal Medicine: Clinical Cases.

Retatrutide is not approved by the FDA, but is available from third-party sources online.

The patient started on a self-determined dose of 10 mg subcutaneously weekly for several weeks, and had recently doubled his dose. The day that his diarrhea began, he forgot that he had taken a dose the day before and accidentally repeated the same 20-mg dose.

When he arrived at the ED, his potassium was low, his sodium was borderline, and he was “profoundly dehydrated,” showing signs of early kidney injury as a result, Komolafe noted. “So, we had to focus on rehydrating immediately.”

“This case report contains a dramatic presentation of unintended consequences from the use of a novel triple-hormone receptor agonist and points toward the need for increased regulatory measures regarding the marketing of these treatments,” Komolafe wrote.

As direct-to-consumer marketing of weight-loss peptides has become increasingly prevalent online, greater scrutiny of these drugs is needed, Komolafe told MedPage Today.

“This medication needs to be available in a more structured setting, and the dosing needs to be individualized,” he said. “It’s never one-size-fits-all.”

GLP-1 receptor agonists are “fantastic drugs, but can also be a double-edged sword,” he added.

Earlier this year, the FDA issued a statement about the risks of unapproved GLP-1 drugs for weight management, noting that it has sent warning letters to companies distributing active pharmaceutical ingredients such as retatrutide and certain other GLP-1 drugs.

Priya Jaisinghani, MD, of NYU Langone Health in New York City, told MedPage Today that “clinicians need to proactively ask patients not just what they’re taking, but where they’re getting it, and counsel on the risks of non-FDA-approved or compounded agents.”

“While there seems to be relative unanimity regarding the medical benefits of [GLP-1 drugs], the risks for unregulated online sales must not be overlooked,” she said.

After taking the extra dose of retatrutide, the patient said he was having bowel movements roughly every 20 to 30 minutes, with up to 30 episodes the day before he came to the ED. His stools were watery, with no mucus or blood present. He was also experiencing intermittent cramping prior to his bowel movements and said he felt feverish. He had taken an anti-diarrheal at home, which had not helped.

The man had no recent hospitalization or antibiotic use, nor any contact with anyone experiencing similar symptoms. He said he had not eaten any food he believed to have been spoiled or contaminated, and he had not recently traveled. He had no family history of inflammatory bowel disease.

In cases of intractable diarrhea, a clinician’s first thought is to ask whether the patient might have an infectious diarrhea, such as norovirus, Komolafe said.

A gastrointestinal multiplex polymerase chain reaction stool panel was negative for Campylobacter, Clostridium difficile, Plesiomonas shigelloides, Salmonella, Escherichia coli, norovirus, rotavirus, and sapovirus, among other bacteria, viruses, and toxins, suggesting no evidence of an infectious cause.

After ruling out an infectious etiology, Komolafe said that he and his colleagues felt comfortable introducing anti-diarrheal agents to reduce the frequency of his bowel movements and get his symptoms under control, while still focusing on replacing his electrolytes and fluid losses.

As his diarrhea improved, his renal function recovered and he was discharged after 4 days in the hospital. The patient was told to discontinue retatrutide.

A week after his discharge, the patient remained well. He was referred to a primary care provider for “structured, holistic, and regulated care for his weight loss concerns.”

As for what might have happened if the patient had not come to the ED, Komolafe said that the concerns are “myriad,” including electrolyte disturbances that could have led to a coma and cardiac arrhythmias. If his renal function had gotten worse, he could have developed severe acute kidney injury requiring dialysis.

“He could have lost his life” if his symptoms weren’t addressed quickly enough, he noted.