This has been a long time coming and the path to get here has been tortured. Nature Medicine published new results of a rigorous phase two study with bimagrumab and semaglutide for obesity. The results are striking because the combination of these two drugs produces improvements in body composition we have never seen before in trials of semaglutide or tirzepatide.

At the highest dose combination tested, people lost 42% of their total body fat mass in 48 weeks of treatment. For comparison, people receiving the full 2.4 mg dose of semaglutide lost 25% of their fat mass.

Moving Beyond Weight

On average in this study, people had a waist circumference of 46 inches. After 48 weeks of the combination at the top dose, that went down by eight inches. This is a very visible sign of a dramatic reduction in visceral fat.

Steven Heymsfield was the lead author on this study. He explained the importance of these findings in bringing a new perspective:

“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 benefit from treatments that maximize fat mass reduction while preserving skeletal muscle. Bimagrumab and semaglutide 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.”

The Tortured Path

Getting to this point has required a great deal of perseverance. Originally, bimagrumab was tested by Novartis for treating pathological muscle loss, weakness, and conditions causing muscle wasting. The drug fell short in those clinical trials. So the company did one clinical study in obesity. After presenting those results at ObesityWeek in 2019 and later publishing them in JAMA Network Open, Novartis dropped the drug and spun it out to a small biotech startup, Versanis Bio. Novartis saw no potential in the market for obesity medicines back then. Oops.

Two years later, when the obesity market was exploding, Lilly bought Versanis for $1.9 billion. This study of bimagrumab and semaglutide had already started and it continued to completion – even though the combination with semaglutide held little interest for Lilly. That’s because it belongs to Novo Nordisk.

Now two phase two studies of bimagrumab in combination with tirzepatide (Lilly’s drug) for obesity are underway. One is due to finish in early 2027, the other finishes in 2029. That will be almost ten years after we first learned that bimagrumab might have promise for treating obesity.

Indeed, this has been a tortured path for important innovation.

Click here for the study in Nature Medicine, here, here, here, and here for further perspective.

Daybreak, painting © by Tim Church, used by permission