Key takeaways:
- Including bimagrumab 30 mg/kg to semaglutide 2.4 mg conferred weight lack of greater than 20% at 72 weeks in sufferers with weight problems.
- Weight reduction occurred with out a vital affect on lean mass.
CHICAGO — The mix of IV bimagrumab and subcutaneous semaglutide was linked to massive reductions in physique weight and fats mass at 72 weeks with no critical affect on lean mass, in response to the outcomes of the BELIEVE trial.
For BELIEVE, offered on the American Diabetes Affiliation Scientific Periods, researchers randomly assigned 507 sufferers with weight problems to considered one of 9 arms: placebo; bimagrumab (Versanis Bio/Eli Lilly) 10 mg/kg; bimagrumab 30 mg/kg; semaglutide 1 mg (Ozempic, Novo Nordisk) plus placebo; semaglutide 2.4 mg (Wegovy, Novo Nordisk) plus placebo; bimagrumab 10 mg/kg plus semaglutide 1 mg; bimagrumab 30 mg/kg plus semaglutide 1 mg; bimagrumab 10 mg/kg plus semaglutide 2.4 mg; or bimagrumab 30 mg/kg plus semaglutide 2.4 mg.
“The mix of bimagrumab and semaglutide resulted in vital fats mass discount, together with visceral fats, whereas lean mass was largely preserved,” Louis J. Aronne, MD, FACP, FTOS, DABOM, the Sanford I. Weill Professor of Metabolic Analysis at Weill Cornell Medication in New York, stated throughout a press convention. “These findings additional assist the investigation of the activin pathway inhibitor … to optimize the diploma and high quality of weight discount for individuals dwelling with weight problems.”
Bimagrumab is “a monoclonal antibody that blocks signaling of activins and [growth differentiation factors] in muscle and adipose tissue,” Aronne stated in the course of the press convention.
“The [growth differentiation factor] that’s most essential known as myostatin. Myostatin and the opposite compounds inhibit muscle progress in skeletal muscle through activin pathways and in addition improve lipid storage in adipose tissue. These are issues that we don’t typically need to see in weight problems. If we might undo that, we might have improved metabolic well being, we imagine. Bimagrumab was designed … to do one thing completely different. What it winds up doing is obstructing these pathways, which results in elevated muscle mass and reduce in fats mass, notably visceral and hepatic fats. There isn’t any urge for food suppression and no hypermetabolism. This has a very completely different mechanism from … semaglutide. There’s potential of sparing the regain of fats due to lack of lean mass. We imagine that is complementary to incretins and different appetite-suppressant compounds,” he stated.
The first therapy interval ran for 48 weeks, after which there was a 24-week extension interval the place all sufferers stayed on their routine apart from the placebo and bimagrumab 10 mg/kg teams, which have been switched to bimagrumab 30 mg/kg, Aronne stated in the course of the press convention.
Bimagrumab was given as an IV infusion as a result of that was its solely supply technique when the trial started, however in subsequent trials, it is going to be given as a subcutaneous injection, Aronne stated.
“The first goal was weight reduction; a further aim was to enhance the standard of weight reduction by maximizing fats mass loss and preserving lean mass,” he stated.
In the course of the presentation, Aronne and Steven B. Heymsfield, MD, FTOS, professor within the division of metabolism and physique composition at Pennington Biomedical Analysis Middle at Louisiana State College, targeted on the outcomes of the three maximum-dose teams: bimagrumab 30 mg/kg, semaglutide 2.4 mg and bimagrumab 30 mg/kg/semaglutide 2.4 mg.
The 72-week outcomes have been as follows:
- physique weight change: bimagrumab 30 mg/kg, –10.8%; semaglutide 2.4 mg, –15.7%; bimagrumab 30 mg/kg/semaglutide 2.4 mg, –22.1%;
- waist circumference change: bimagrumab 30 mg/kg, –13.3 cm; semaglutide 2.4 mg, –14.7 cm, bimagrumab 30 mg/kg/semaglutide 2.4 mg, –21.7 cm;
- whole physique fats mass change: bimagrumab 30 mg/kg, –28.5%; semaglutide 2.4 mg, –27.8%; bimagrumab 30 mg/kg/semaglutide 2.4 mg, –45.7%;
- estimated visceral adipose tissue change: bimagrumab 30 mg/kg, –45.1%; semaglutide 2.4 mg, –35.8%; bimagrumab 30 mg/kg/semaglutide 2.4 mg, –58.2%;
- whole physique lean mass change: bimagrumab 30 mg/kg, +2.5%; semaglutide 2.4 mg, –7.4%; bimagrumab 30 mg/kg/semaglutide 2.4 mg, –2.9%;
- share of weight reduction because of fats mass: bimagrumab 30 mg/kg, 100%; semaglutide 2.4 mg, 71.8%; bimagrumab 30 mg/kg/semaglutide 2.4 mg, 92.8%;
- share of sufferers with at the least 30% discount in fats mass: bimagrumab 30 mg/kg, 50%; semaglutide 2.4 mg, 36.4%; bimagrumab 30 mg/kg/semaglutide 2.4 mg, 94%;
- high-sensitivity C-reactive protein change: bimagrumab 30 mg/kg, –70.1%; semaglutide 2.4 mg, –59.1%; bimagrumab 30 mg/kg/semaglutide 2.4 mg, –83.4%;
- whole ldl cholesterol change: bimagrumab 30 mg/kg, +10.1%; semaglutide 2.4 mg, –4.4%; bimagrumab 30 mg/kg/semaglutide 2.4 mg, –2.1%; and
- triglycerides change: bimagrumab 30 mg/kg, +2.3%; semaglutide 2.4 mg, –21%; bimagrumab 30 mg/kg/semaglutide 2.4 mg, –25.2%.
As well as, at 48 weeks, ranges of adiponectin, which have been proven to be protecting in opposition to diabetes and coronary heart illness, elevated 29 µg/mL within the bimagrumab 30 mg/kg group, 7.2 µg/mL within the semaglutide 2.4 mg group and 37.9 µg/mL within the bimagrumab 30 mg/kg/semaglutide 2.4 mg group, in response to the researchers.
The quantity of weight reduction within the bimagrumab 30 mg/kg/semaglutide 2.4 mg group is much like that seen with tirzepatide (Zepbound, Eli Lilly) and cagrilintide 2.4 mg/semaglutide 2.4 mg (CagriSema, Novo Nordisk), however the share of weight reduction from fats mass was a lot increased than for tirzepatide or semaglutide, Aronne stated.
LDL accounted for a lot of the change in whole ldl cholesterol, Heymsfield stated in the course of the press convention.
“Widespread hostile occasions included muscle spasms, diarrhea, zits with bimagrumab, and nausea, constipation and fatigue with semaglutide. There have been no critical hostile cardiac occasions,” Aronne stated in the course of the press convention.
A 32-week therapy withdrawal interval is ongoing, Aronne stated in the course of the press convention. “Our hope is that we are going to see higher upkeep of weight reduction over that time frame,” he stated.
A trial evaluating the mixture of bimagrumab and tirzepatide is underway, Aronne stated in the course of the presentation of the BELIEVE findings.
Perspective
This examine was very fascinating. Clinically, what we begin to fear about now with long-term use of those therapies is lack of muscle mass. I feel this can be a very fascinating strategy to deal with that medical barrier. There are different approaches in improvement as properly, and we have to see how the info play out with all of the completely different choices. However that is promising, and I stay up for extra knowledge.
Joshua J. Neumiller, PharmD, CDCES, FADCES, FASCP
Disclosures: Neumiller reviews no related monetary disclosures.
Sources/Disclosures
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Heymsfield SB, et al. Symposium – Can we enhance the standard of weight reduction by augmenting fats mass loss whereas preserving lean mass? The BELIEVE examine of bimagrumab + semaglutide. Offered at: American Diabetes Affiliation Scientific Periods; June 20-23, 2025; Chicago.
Disclosures:
The examine was funded by Versanis Bio, which was acquired by Eli Lilly in the course of the course of the trial. Aronne reviews consulting for and receiving analysis assist from Eli Lilly and Novo Nordisk. Heymsfield reviews no related monetary disclosures.
