GLP-1 weight loss drugs effective even at low starter doses#-glp-1-weight-loss-drugs-effective-even-at-low-starter-doses
REUTERS Aug-31-2026 6:23 p.m. ET By Nancy Lapid
* Full doses of GLP-1 drugs may not always be necessary
* Patients lose weight on lowest doses but to a lesserextent
* Low-dose GLP-1 treatment does not prevent side effects
Aug 31 (Reuters) - New research indicates that individuals using widely prescribed GLP-1 obesity medications who stay at low initial doses can still shed some pounds, yet they might also encounter adverse reactions—though with notably reduced nausea compared to those who move up to the higher doses recommended by manufacturers.
Moreover, the study discovered, they are not likely to achieve the double-digit percentage weight reductions observed at those higher doses.
The GLP-1 medications semaglutide, marketed as Ozempic and Wegovy by Novo Nordisk, along with Eli Lilly's (LLY) tirzepatide, available under the brand names Mounjaro and Zepbound, are initially prescribed at a low dose and then gradually increased to higher doses, which helps the body adapt and lessens side effects.
Due to factors like tolerability, availability, expense, supply constraints, or personal objectives, numerous patients never reach the advised maintenance dose.
Data from 534 patients who kept using injectable semaglutide at the 0.25-milligram starting dose for a minimum of six months was examined by researchers, alongside an equal number of patients who remained on tirzepatide at the 2.5-mg starter dose for at least the same duration.
After one year, the average percentage of body weight reduction on these lowest approved doses was 5.5% for tirzepatide and 2.2% for semaglutide, according to the researchers' report on Monday in Biology Methods & Protocols.
In contrast, an earlier direct comparison trial showed that at one year, average weight loss on the recommended higher doses was 20.2% for tirzepatide and 13.7% for semaglutide.
The observation that patients who never went beyond the initial dose still experienced some weight loss implies these drugs possess a detectable pharmacological impact considerably under the maintenance doses that clinical trials were designed around, according to Venky Soundararajan, the study's lead author from the data analytics company nference.
Semaglutide is presently regarded as superior for kidney health since it has U.S. approval to lower the risk of worsening chronic renal disease. Tirzepatide has not yet received specific approval for kidney protection.
Even at reduced doses, kidney outcomes proved superior with semaglutide, Soundararajan pointed out.
After two years, low-dose tirzepatide was linked to increased rates of kidney injury in 2.7% of patients, compared to 0.4% with semaglutide.
The Lilly medication was also tied to more instances of constipation (32.6% vs 22.4%), muscle cramps (8.3% vs 4%), lumbar disc disease (3.3% vs 0.3%), shortness of breath during exertion (9.6% vs 6.8%), and other negative events.
Those on prolonged low-dose semaglutide experienced higher rates of ear inflammation (5.6% vs 2.1% with tirzepatide), excessive sweating (5.5% vs 3.2%), and ankle swelling (6.9% vs 3.7%).
The study revealed that patients who stayed on the starter doses did have considerably less nausea and constipation than what has been documented for patients on higher doses.
Soundararajan noted that observational studies like this cannot establish cause and effect.
A clinical trial was recently initiated by Novo Nordisk to assess lower maintenance doses of its Wegovy pill, but findings will not be available for several years.
"In the meantime, with real-world patients taking lower-than-recommended doses, there's a need for awareness," Soundararajan said.
"These two medicines are not equivalent," he continued. "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."
