Abstract
BACKGROUND: Tirzepatide, a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, has gained widespread use for the treatment of type 2 diabetes mellitus, obesity, and obstructive sleep apnea. This report presents the first probable case of tirzepatide-associated rhabdomyolysis in a human immunodeficiency virus (HIV)-positive patient. CASE: A 34-year-old male with a medical history of HIV, hypertension, and obesity presented with fatigue, muscle aches, and dark-colored urine. The symptoms had progressively worsened over the prior 2 weeks, coinciding with the recent initiation of tirzepatide therapy for weight loss. Laboratory tests revealed significantly elevated creatine kinase (CK) levels, transaminitis, and myoglobinuria, confirming the diagnosis of rhabdomyolysis. The patient reported no history of trauma, strenuous physical activity, or statins use. Tirzepatide was discontinued, the patient was managed successfully with aggressive intravenous fluids, discharged in stable condition. DISCUSSION: This case represents a rare but serious adverse effect potentially associated with tirzepatide use, particularly in HIV-positive patients, who may be at increased risk for muscular disorders. While other common causes of rhabdomyolysis were ruled out, the timeline between tirzepatide initiation and symptom onset strengthens the case for a medication-induced etiology. This is one of only a few reported cases of tirzepatide-induced rhabdomyolysis, with no previous documentation in HIV patients. CONCLUSION: Rhabdomyolysis may be a rare but significant adverse effect of tirzepatide, particularly in at-risk populations, such as those with HIV. Clinicians should remain vigilant for rhabdomyolysis in patients presenting with nonspecific symptoms such as muscle pain, fatigue, and dark urine in patients on tirzepatide or other GLP-1 agonists.