A phase 2 clinical trial published in Nature Medicine suggests that apitegromab, a monoclonal antibody, may help individuals taking tirzepatide retain more lean body mass without reducing overall weight loss, according to findings released on June 9.
The randomized, double-blind EMBRAZE trial enrolled participants between June and September 2024. Researchers assigned 102 adults with overweight or obesity to receive either apitegromab or placebo alongside up to 15 mg of tirzepatide weekly. Participants were aged between 18 and 65 years and met specific body mass index criteria. The study excluded people with diabetes, heart disease, stroke, blood vessel disorders, active cancer, recent chemotherapy or immunosuppressive therapy, and those who had used antiobesity or antidiabetic medications recently.
Researchers measured changes in lean body mass using dual-energy X-ray absorptiometry (DEXA) scans at week 24 for both groups—43 receiving apitegromab and 44 receiving placebo. They also monitored trunk fat levels and other secondary endpoints such as vital signs and laboratory findings throughout the study period.
After six months of treatment, individuals given apitegromab lost less lean mass than those given placebo while achieving similar overall weight loss. On average, recipients maintained nearly two kilograms more lean mass than the placebo group. The data showed that about 85% of total weight loss in the apitegromab group was fat compared to approximately 70% in the placebo group. Trunk fat changes were similar between groups.
The durability of these effects was evaluated eight weeks after discontinuation of interventions; differences in lean mass remained significant, but this analysis was exploratory. Both groups experienced adverse events at similar rates—over seventy percent—but serious adverse events occurred infrequently (about two percent), with none attributed to apitegromab use. Nausea, fatigue, and headache were reported more often among those taking apitegromab.
Researchers said further studies are needed with larger sample sizes and longer follow-up periods, including populations with obesity-related conditions such as diabetes or cardiovascular disease, to confirm these results in broader settings. "Because this was a small phase II trial based primarily on completers and using eighty percent confidence intervals without multiplicity adjustment," they wrote, "the findings should be interpreted as proof of concept rather than definitive evidence of clinical benefit."
