A new drug, called bimagrumab, in a phase 2 trial,(1) resulted in a more than 20% loss of fat mass while at the same time actually increasing lean body mass by 3.6%. There was also a decrease in waist circumference of 3.5 inches and a big improvement in hemoglobin A1C the standard indicator of diabetes control. The study group of 58 people with obesity and type 2 diabetes were treated over a period of 48 mos, half got bimagrumab by intravenous infusions and half got placebo. The trial was conducted at 9 medical centers in the US and UK by Novartis, the drug company that holds the patent on bimagrumab. These are impressive and highly unusual results for a weight loss drug.
Drug names ending with “-mab” are monoclonal antibodies. These are immune proteins made in genetic clones of white cells engineered to be aimed at a specific receptor. Bimagrumab is aimed at the activin type II receptor (ActRII). This receptor, when stimulated, blocks skeletal muscle growth. So when bimagrumab attaches to activin receptors on muscle cells, that blocks the blockade of muscle growth which increases muscle growth. This receptor also is found in lots of other places and obviously does lots of other things not much of which are understood yet.
Phase 2 studies use the maximum safe dose of a new drug as determined by phase 1 studies and also tests for the effectiveness of the drug for the uses desired. Phase 3 studies use lots more study subjects and check for more long term safety – way more expensive and only done for the most promising candidates.
Bimagrumab may not be safe enough but it illustrates my contention that although obesity is very complicated there may well be some day a magic bullet that bypasses all the complications and works safely and wonderfully.
Bimagrumab was initially tried as a treatment for muscle wasting that is caused by many terrible diseases – cancer, AIDS, heart and kidney disease… But in phase (almost) 3 trials it caused a scary muscle disease called inclusion body myositis and was pulled for that. In this trial for obesity and type 2 diabetes they didn’t mention any myositis but one patient got pancreatitis which is serious though the patient recovered.
The other thing this new magic bullet did was highly unusual for weight loss. When you lose weight by not eating or by the other weight loss drugs or by gastric bypass surgery about a quarter of the weight lost is from lean body mass. Some of that lean tissue is in the three quarters loss of the body fat mass – fat does have some lean tissue component. Some little bit of that lean body loss can be prevented by exercise during weight loss. But some is inevitably lost from vital lean body tissues like your heart. Also since muscle weighs more that fat, twenty plus percent fat loss and 4% muscle gain resulted in only 6.5% total body weight loss. That means we should not hang so much on what the scale says.
Maybe bimagrumab is a magic exercise drug that skips the pain of running?
1. Heymsfield SB, et al. Effect of Bimagrumab vs Placebo on Body Fat Mass Among Adults With Type 2 Diabetes and Obesity
A Phase 2 Randomized Clinical January 13, 2021, JAMA Netw Open. 2021;4(1):e2033457. doi:10.1001/jamanetworkopen.2020.33457
Bimagrumab: Hesitancy and Promise in Obesity Care – ConscienHealth
Bimagrumab: Hesitancy and Promise in Obesity Care. Innovation in obesity care has come a long way. Back in 2010, Sanofi was smarting from the spectacular failure of rimonabant and big pharma was closing down research programs in obesity.But Novo Nordisk forged ahead with an ambitious program and now has a successful portfolio in obesity care to show for it.
This writer’s opinion is their own and not the opinion of this newspaper
John DiTraglia M.D. is a Pediatrician in Portsmouth. He can be reached by e-mail- firstname.lastname@example.org or phone-354-6605.