Low-Dose GLP-1 Drugs Still Aid Weight Loss, But Side Effects Differ

A new observational study suggests that patients who remain on the lowest starter doses of popular GLP-1 obesity drugs can still achieve meaningful, albeit modest, weight loss—though the side-effect profiles of the two leading medications differ significantly.

The research, published in Biology Methods & Protocols, analyzed 534 patients who stayed on a 0.25-mg weekly dose of semaglutide (sold as Ozempic and Wegovy) for at least six months, and an equal number who remained on a 2.5-mg dose of tirzepatide (Mounjaro and Zepbound).

After one year, patients on the low tirzepatide dose lost an average of 5.5% of their body weight, while those on low-dose semaglutide lost 2.2%. For context, earlier head-to-head trials of the full maintenance doses showed average weight losses of 20.2% for tirzepatide and 13.7% for semaglutide.

Study leader Venky Soundararajan of data analytics firm nference noted that the findings demonstrate a measurable pharmacological effect even at doses far below those used in clinical trials. Many patients never escalate to maintenance doses due to cost, supply issues, tolerability, or personal goals.

The study also highlighted important differences in adverse events. Low-dose tirzepatide was linked to higher rates of kidney injury (2.7% vs 0.4% for semaglutide at two years), constipation (32.6% vs 22.4%), muscle cramps, lumbar disc disease, and shortness of breath. Low-dose semaglutide, meanwhile, was associated with more ear inflammation, heavy sweating, and ankle swelling.

Patients on either low dose experienced substantially less nausea and constipation than is typically reported at higher doses. Soundararajan cautioned that observational studies cannot prove cause and effect, but stressed the need for awareness as real-world use of lower-than-recommended doses becomes common.

"These two medicines are not equivalent," he said. "Patients who are not aiming for 20% or 30% weight loss need to know there's a chance they can lose a little weight on these low doses, and they deserve to know the picture around the adverse event profile."

Novo Nordisk has launched a trial to evaluate lower maintenance doses of its oral Wegovy formulation, though results are not expected for several years.