Preserving muscle: GLP1s with Bimagrumab
We deep dive on Bimagrumab, a muscle-preserving booster to GLP1 receptor agonists like Ozempic, Wegovy, Mounjaro, Zepbound and others.
One of the largest complaints and perceived risks when taking GLP1s has been the negative side effect of muscle loss. Similar to other somewhat "surface" side effects, muscle loss is mostly attributable to massive weight loss more than GLP1s in particular.
To put it simply, losing weight normally means losing muscle, and since GLP1s curb appetite (amongst other things), those who do not consume enough protein and/or stay active (or increase activity to include some resistance training) are likely to lose muscle along with fat.
Regardless of this truth, the advent of "boosters" that are meant to be taken along with GLP1s are steadily growing in popularity, and one of the upcoming drugs under development by Novartis called Bimagrumab intends to treat muscle loss for people taking GLP1s.
Bimagrumab, in combination with Semaglutide/Tirzepatide or other GLP1s promises to make make an already effective weight loss mechanism even better by helping retain muscle.
The recent 85th ADA Scientific Sessions conference also revealed some huge impovements:
What is Bimagrumab?
Bimagrumab is an antibody that prevents the activation of activin receptor type 2B:
Contributors to Wikimedia projects
So what is Activin Receptor type 2B, and why would you want to stop it from being activated?
Contributors to Wikimedia projects
Activin receptor Type 2B does a lot of things, but one of the things it does is negatively affect muscle growth – so this means that when activated, it reduces muscle growth.
So, by reducing the activation of receptor Type 2B, the idea is that muscle loss can be prevented.
Bimagrumab has been found to go further than just increasing muscle ("skeletal muscle", in the literature) but also having an effect on fat ("brown adipose tissue"), and other complimentary effects to GLP1 receptor agonists.
Is Bimagrumab safe?
Some of the earliest research into Bimagrumab was not in the type 2 diabetes or weight loss space at all – it was related to whether it could be taken safely as a treatment for inclusion body myositis, a disease of skeletal muscle:
Michael G Hanna
This study outlines the relative safety of taking Bimagrumab:
- Falls were common for the , but there were more falls in the placebo group than the Bimagrumab group
- The major adverse event in the Bimagrumab group was muscle spasms
- No deaths were linked to Bimagrumab
The interpretation portion covers this succinctly:
Interpretation: Bimagrumab showed a good safety profile, relative to placebo, in individuals with inclusion body myositis but did not improve 6MWD. The strengths of our study are that, to the best of our knowledge, it is the largest randomised controlled trial done in people with inclusion body myositis, and it provides important natural history data over 12 months.
While Bimagrumab did not provide improvements in the intended outcome (6 Minute Walking Distance, "6MWD"), it was relatively safe for people to take.
Is Bimagrumab effective (ex. as a "booster" for GLP1s)?
Like GLP1s, research into Bimagrumab has been performed in the past and is under way currently – there is lots of literature to consult to figure out what it's effect has been when used.
In 2021, there was a trial done on standalone use of Bimagrumab to see it's effect on body fat mass:
Steven B Heymsfield
While there were only a small number of participants, the results of this trial were quite positive:
In this phase 2 randomized clinical trial, ActRII blockade with bimagrumab led to significant loss of [Fat Mass], gain in [Lean Mass], and metabolic improvements during 48 weeks in patients with overweight or obesity who had type 2 diabetes.
In 2024, a review and mice model research was published:
Manmeet Kaur
Elizabeth Nunn
In the mouse model, the results were quite outstanding:
Treatment of obese mice with bimagrumab induced a ∼10 % increase in lean mass while simultaneously decreasing fat mass. Daily treatment of obese mice with semaglutide potently decreased body weight; this included a significant decrease in both muscle and fat mass. Combination treatment with bimagrumab and semaglutide led to superior fat mass loss while simultaneously preserving lean mass despite reduced food intake.
Eli Lilly is even currently enrolling for a trial about the interaction of Bimagrumab and Tirzepatide:
Eli Lilly
The most recent research
Recently the ADA had it's 85th Scientific Sessions conference, and the results that were achieved with Bimagrumab and Semaglutide were amazing:
While not fully yet available, the results from the BELIEVE Phase 2b trail were announced, with some key details:
- 507 participants received semaglutide as a once-weekly subcutaneous injection and/or bimagrumab administered via intravenous (IV) infusion at weeks 4, 16, 28, and 40.
- The primary endpoint was change in body weight (BW) from baseline.
- Secondary endpoints included changes in waist circumference, total body fat mass, visceral adipose tissue, and lean mass.
Normally this trial would be redundant with previous ones, but the inclusion of Bimagrumab gives us a view into the distribution of weight loss.
The results were spectacular.
Notably, with the use of bimagrumab alone, 100% of weight loss was attributed to fat mass and there was an increase of 2.5% total lean mass.
An increase of 2.5% in muscle ("lean mass") is outstanding, along with having the weight loss be completely attributable to fat mass.
This is an absolute game changer as a combination therapy for GLP1s.
What does this mean for GLP1s?
One of the biggest complaints/risks about GLP1s is going away – adding in Bimagrumab seems to be increasing the likelihood of people retaining muscle while taking GLP1s, and that is great for patients who are on GLP1s.
While as of yet untested, this effect is likely to extend to all GLP1s (as they're effective in similar ways), and be beneficial to the use of Liraglutide, Semaglutide, Tirzepatide, and may other peptides.
