Sustained Low-Dose Semaglutide Is Linked to Broad-Spectrum Cardiometabolic Benefits, and Better Tolerability Profile over Low-Dose Tirzepatide, Motivating Semaglutide Microdosing Studies
Preprints.org June 9, 2026 Karthik Murugadoss, A.J. Venkatakrishnan, Venky Soundararajan preprint
In routine care, many patients taking semaglutide or tirzepatide do not reach recommended maintenance doses. Using electronic health records from 29 million patients, researchers identified 814 individuals who sustained very low doses of semaglutide (0.25 mg) or tirzepatide (2.5 mg) for at least six months. Over 24 months, low-dose tirzepatide showed a worse adverse event profile than low-dose semaglutide, including higher rates of constipation (32.6% vs 22.4%), acute kidney injury (2.7% vs 0.4%), and muscle cramps (8.3% vs 4%). Low-dose tirzepatide also led to greater weight loss. Low-dose semaglutide was associated with broad cardiometabolic benefits despite minimal weight change, and better tolerability than low-dose tirzepatide.