In June 2021, the FDA approved semaglutide, a highly anticipated pharmaceutical treatment for obesity. This marked the first weight-loss drug to hold real promise after a decades-long history of ineffective and, at times, dangerous (fen-phen) drugs being brought to market. Now another drug, bimagrumab, seems likely to be added to the list of safe and effective weight loss drugs.
Results of a recent phase 2 clinical trial published in JAMA show overweight/obese individuals treated with bimagrumab lost 20% more fat mass, on average, as compared to individuals taking a placebo. Participants were administered bimagrumab or placebo via intravenous infusion every 4 weeks for a total of 48 weeks. Although individual results varied, over three-quarters of participants receiving bimagrumab lost at least 15% of their fat mass.
Evidence has shown that differing depots of fat have varied metabolic and inflammatory effects, playing a part in dictating overall health outcomes. In general, leaner individuals have been associated with improved health and a lower risk of disease; however, subcutaneous (below the skin) fat is considered to be more innocuous. Visceral (surrounding the organs) and hepatic (within the liver) fat are considered to be more deleterious lipid storage compartments and are associated with increased metabolic disease and risk of mortality. Importantly, this study reported fat mass reductions to be universal and not isolated to the more benign subcutaneous depot.
In addition to reduced adiposity, treatment with bimagrumab showed improvement to a variety of weight-associated health parameters. Prior to treatment, all study participants were determined to have a clinical diagnosis of type 2 diabetes. Type 2 diabetes is associated with dysregulated glucose metabolism resulting in elevated HBA1C levels. At the termination of the study, bimagrumab-treated subjects were observed to have a beneficial reduction of HBA1C levels. Although there was no significant improvement to insulin sensitivity in this trial, previous clinical studies have shown improvements ranging from 20% to 40%—assessed by either glucose tolerance test or euglycemic clamp.
Bimagrumab, being a monoclonal antibody therapeutic, acts by binding to specific proteins and altering their function. Specifically, bimagrumab binds to and inhibits the activin type II receptor and as a result stimulates muscle growth. Originally developed as a sarcopenia therapeutic, it failed to prevent muscle wasting and weakness in elderly subjects of previous clinical trials. However, in this study participants experienced a 3.7% increase in lean body mass. This is significant considering that the majority of dietary interventions to control obesity often have the undesirable effect of reducing lean body mass. Loss of lean body mass with age is highly associated with increased risk of mortality—recent studies report the preservation of lean body mass and insulin sensitivity are critical components of chronic calorie restriction’s imparted healthspan benefits.
Obesity is highly correlated with and thought to contribute to an increased incidence of heart disease, stroke, type 2 diabetes, and certain cancers and is rapidly becoming the most prevalent driver of age-related pathologies in the modern world. A 2018 analysis of obesity in the US reported a 33% percent increase in incidence as compared to the previous decade. With the exception of surgical interventions, medical treatment of obesity has been ineffective and primarily relegated to dietary interventions that are difficult to adhere to and suffer from a lack of long-term compliance. The availability of novel pharmaceutical interventions, such as bimagrumab, might provide treatment to the increasingly common condition of intractable obesity.