GLP-1 weight loss drugs effective even at low starter doses

People taking popular GLP-1 obesity drugs ‌who ​remain on low starter doses will lose some weight but may still experience side effects, although significantly less nausea than those who graduate to higher manufacturer-recommended doses, a new study suggests.

And they are unlikely to experience the double-digit weight-loss percentages seen ‌with the higher doses, the study found. The GLP-1 drugs semaglutide, sold as Ozempic and Wegovy by Novo Nordisk, and Eli Lilly's tirzepatide, sold under the brand names Mounjaro and Zepbound, are prescribed initially at a low dose followed by gradual titration to higher doses, to help the body adjust and minimize side effects.

Many patients never achieve the recommended ‌maintenance dose due to tolerability, access, cost, supply or their individual goals. Researchers analyzed data on 534 patients who continued to take injectable semaglutide at the 0.25-milligram starter ‌dose for at least six months, and the same number of patients who stayed on tirzepatide at the 2.5-mg starter dose for at least that long.

At one year, the percentage of body weight lost on these lowest approved doses averaged 5.5% with tirzepatide and 2.2% with semaglutide, researchers reported on Monday in Biology Methods & Protocols. By comparison, the average weight loss at one year on recommended higher doses was 20.2% with ⁠tirzepatide and ​13.7% with semaglutide in an earlier head-to-head trial.

The ⁠finding that patients who never escalated past the initiation dose still lost some weight suggests the drugs have a measurable pharmacologic effect well below the maintenance doses that clinical trials have been built around, ⁠said study leader Venky Soundararajan of data analytics firm nference. Semaglutide is currently considered better for kidneys because it has received U.S. approval to reduce the risk of worsening chronic renal disease. ​Tirzepatide is not yet approved specifically for kidney protection.

Even at the lower doses, kidney outcomes were better with semaglutide, Soundararajan noted. Low-dose tirzepatide was associated with ⁠higher rates of kidney injury after two years in 2.7% of patients versus 0.4% with semaglutide.

The Lilly drug also was associated with more constipation (32.6% vs 22.4%), muscle cramps (8.3% vs 4%), lumbar disc disease (3.3% vs 0.3%), shortness ⁠of ​breath on exertion (9.6% vs 6.8%), and other adverse events. Patients on sustained low-dose semaglutide had higher rates of ear inflammation (5.6% vs 2.1% with tirzepatide), heavy sweating (5.5% vs 3.2%) and ankle swelling (6.9% vs 3.7%).

Patients who remained on the starter doses did have substantially less nausea and constipation than has been reported for patients taking higher doses, ⁠the study found. Observational studies such as this one cannot prove cause and effect, Soundararajan noted.

Novo Nordisk recently launched a clinical trial to evaluate lower maintenance doses of its ⁠Wegovy pill, but results are years away. "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.”