A recent research study found that\u00a0a combination of the GLP-1 receptor agonist semaglutide and\u00a0bimagrumab, an antibody that blocks activin signaling pathways, results in greater weight loss while also preserving lean mass, such as skeletal muscle and connective tissue. In the paper “Bimagrumab and semaglutide alone or in combination for the treatment of obesity: a phase 2 randomized clinical trial,” published Monday in the journal Nature Medicine, Dr. Steven\u00a0Heymsfield\u00a0of Pennington Biomedical Research\u00a0Center\u00a0describes the results of the BELIEVE study,\u00a0which showed that the therapy combination addressed lean mass loss associated with GLP-1-based therapies.<\/p>\n
GLP-1-based therapies have been\u00a0highly successful\u00a0in reducing weight, but up to 40% of weight lost may come from lean mass. However, the study described in the paper\u00a0indicates\u00a0that the combination of semaglutide with\u00a0bimagrumab\u00a0delivered substantial weight loss over 72 weeks with lean mass preserved.<\/p>\n
“Obesity treatment has traditionally focused on the number on a scale. Patients with obesity who are at risk for low muscle mass, affecting both physical and metabolic function, may\u00a0benefit\u00a0from treatments that maximize fat mass reduction while preserving skeletal muscle,” said\u00a0Heymsfield, who is an LSU Boyd Professor and director of the Metabolism and Body Composition Laboratory. “Bimagrumab\u00a0and\u00a0semaglutide work through distinct biological pathways, and when combined, we observed not only a preservation of lean mass but also an additive reduction in fat mass that exceeded what either therapy achieved alone.”<\/p>\n
Study participants were divided into groups, with some receiving\u00a0bimagrumab\u00a0only, some receiving semaglutide only, and others receiving the combination. Participants receiving only\u00a0bimagrumab\u00a0saw an average weight loss of 10.8%, with all weight loss attributable to fat mass and lean mass increasing by 2.5%. Those receiving only semaglutide lost an average of 15.7% of body weight, with 71.8% of the loss from fat mass. Participants receiving the drug combination lost an average of 22.1% of body weight, with 92.8% of the weight loss composed of fat mass while lean mass was\u00a0largely preserved.<\/p>\n
The double-blind, placebo-controlled study administered the drugs at two dosing levels for each \u2013 10 or\u00a030 mg\/kg of\u00a0bimagrumab\u00a0and 1.0 or 2.4 mg of semaglutide \u2013 used alone or in combination. These various combinations and doses resulted in nine randomized groups.\u00a0Bimagrumab\u00a0doses were administered every\u00a012 weeks\u00a0while semaglutide doses were administered weekly.<\/p>\n
In addition to weight loss, participants\u00a0demonstrated\u00a0up to an 83% decrease in high-sensitivity C-reactive protein (hsCRP), a key marker of inflammation linked to cardiovascular risk, and a substantial increase in adiponectin, a protein hormone that supports insulin sensitivity, fat\u00a0metabolism\u00a0and anti-inflammatory processes. In a subgroup of participants with indicators of prediabetes, some of the two-drug\u00a0combination\u00a0therapy groups had 100% reversion to normoglycemia among participants with prediabetes at baseline,\u00a0essentially moving\u00a0them to a\u00a0nonprediabetes\u00a0status.<\/p>\n
The drug combination was\u00a0generally well\u00a0tolerated, with side effects consistent with the known profiles of the individual drugs. The trial\u00a0demonstrated\u00a0positive results in terms of both lean mass\u00a0retention and weight loss, but researchers recommend continued clinical development and refinement of the drug combination to better understand the common adverse events\u00a0observed\u00a0in the\u00a0bimagrumab\u00a0groups, such as mild-to-moderate acne and muscle spasms. The study also points to a need for researchers to shift focus from weight and body mass index to other measurements such as body composition as more informative indicators of\u00a0optimal\u00a0obesity management.<\/p>\n
Eli Lilly and Company funded the study, which was designed by\u00a0Versanis\u00a0Bio, a wholly owned subsidiary of Eli Lilly and Company.\u00a0Versanis\u00a0Bio oversaw the clinical trial and partially funded the study before its acquisition by Lilly.<\/p>\n
Source:<\/p>\n
Pennington Biomedical Research Center<\/a><\/p>\n Journal reference:<\/p>\n