Atlas and the Hesperides

Tantalizing: Bimagrumab, Obesity, and Body Composition

It was a stunning and unique result that seemed to come out of nowhere at ObesityWeek late last year. A new drug, bimagrumab, yielded a 21 percent reduction in fat mass after 48 weeks. But lean body mass went up by 3.6 percent. This result is distinctly different from what usually happens in obesity treatment. Usually, although fat mass goes down faster than muscle mass, when people lose weight, they lose both fat and lean body mass.

Because of this distinction, bimagrumab generated a lot of excitement when these results emerged.

A Breakthrough Drug That Previously Failed

The story of bimagrumab is looking like a comeback right now. Back in 2013, the FDA designated bimagrumab as a breakthrough therapy for treating a rare muscle-wasting disease. It’s a monoclonal antibody that stimulates muscle growth by binding activin receptors. Thus, researchers had hoped that it would slow or reverse muscle wasting.

However, great promise sometimes leads to great disappointment. Almost four years ago, bimagrumab failed a pivotal phase 2b study for muscle wasting. It was safe and well-tolerated. But it simply did not work for this purpose.

Moving On from Failure

That could have been the end of the story for this drug, but the company behind it (Novartis) pressed on with studies in patients with insulin resistance and overweight or obesity. In 2017, they published encouraging results from a very small study. In 16 subjects randomized to either bimagrumab or placebo, they found a 2.7 percent increase in lean body mass and a 7.9 percent reduction in fat mass after just ten weeks of treatment. These were patients with an average BMI of 29.3. None of them had actual type 2 diabetes.

So the latest study was bigger and it was done in patients with type-2 diabetes. BMI was higher, ranging from 28 to 40. And the results are impressive because of the improvements in body composition, as well as in HbA1c – an important marker of diabetes control.

Different from Typical Results in Obesity Treatment

Even with the most effective treatment for obesity – bariatric surgery – body composition does not improve in this way. A recent study found that people lose lean body mass in the first year after bariatric surgery. For the next four years, women tended to lose a little more lean body mass, while men held steady.

Make no mistake, the results with bimagrumab are distinctly different. The 21 percent reduction in fat mass might not be as great as the reduction in fat mass after bariatric surgery. But the increase of 3.6 percent in lean mass with bimagrumab is very different from the approximately 10 percent loss that might be seen after surgery.

Early Days

As tantalizing as this data is, we must remember that these are still early days for this drug. Monoclonal antibodies are tricky. Surprises are possible. We have only one year of data in 75 patient and it hasn’t been peer reviewed yet.

We will eagerly wait for more definitive results.

Click here for the study of bimagrumab in insulin resistance and here for the abstract from ObesityWeek. For more on changes in body composition after bariatric surgery, click here and here.

Atlas and the Hesperides, painting by John Singer Sargent / WikiArt

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January 6, 2020