Posted on 05/29/2024 12:46:08 PM PDT by Red Badger
While GLP-1 agonists help people lose weight, different drugs could help them retain muscle at the same time.
Anti-obesity drugs cause people to lose more than just fat.
More than 73% of American adults are overweight, according to the CDC. This puts them at increased risk of death and many serious health issues, but losing weight and keeping it off through diet changes and exercise — the standard approach — is notoriously difficult.
That made the FDA’s 2021 approval of Novo Nordisk’s semaglutide (Wegovy) as an obesity treatment seem like something of a miracle.
The drug is in a class known as GLP-1 agonists, which were created to treat type 2 diabetes. Because they reduce appetite and trigger the release of insulin, they also have a proven ability to help people shed pounds, reduce blood pressure and cholesterol, and even reduce the risk of death.
The problem is that all pounds are not created equal.
Generally speaking, weight loss only occurs when your body needs more calories than you are eating. To make up the difference, your body taps into the energy stored in your fat cells. This causes the fat cells to shrink, and you lose weight.
Your body doesn’t just pull energy from fat, though — it also pulls it from “lean mass,” such as muscle tissue. All ways of losing weight, including dieting, typically involve losing muscle mass as well as body fat. But if you lose too much muscle, you can experience fatigue and a slower metabolism.
In older people, who are already experiencing normal muscle loss due to aging, losing too much muscle mass could potentially reduce mobility and increase the risk of falls.
“Just because we’re losing weight doesn’t always mean we’re getting healthier,” Michelle Hauser, obesity medicine director of the Stanford Lifestyle and Weight Management Center, told the New York Times.
Strength training and eating a high-protein diet can combat muscle loss if you’re losing weight using traditional methods — in those instances, a person can expect the weight they lose to be about 25% lean mass and 75% fat mass.
People just taking GLP-1 agonists may simply be eating less, though, and in studies, 20-40% of the weight they’re losing is muscle mass. This is inspiring drug developers to hunt for another kind of miracle cure: a medication that can prevent muscle loss while you lose weight.
Especially for older adults — who have the most to gain from a drug that lowers the risk of heart disease but also need to preserve muscle strength — combining a muscle-preserving drug with GLP-1 agonists could be a big deal.
Here are four of the most promising candidates:
The anti-aging med
The drug: BioAge Labs’ azelaprag is a drug that mimics the activity of apelin, a natural hormone secreted during exercise that helps regulate metabolism and promotes muscle regeneration.
The details: BioAge began developing azelaprag as an anti-aging medication, because the expression of apelin tends to decrease as we get older — one possible reason we lose muscle as we age. In a trial of 21 healthy seniors confined to bed rest for 10 days, it was well-tolerated and demonstrated an ability to reduce muscle atrophy compared to a placebo.
In studies on obese mice, combining azelaprag with Eli Lilly’s weight-loss drug, tirzepatide, actually resulted in more weight loss than tirzepatide alone. It also improved muscle function and body composition.
In October 2023, BioAge announced plans to collaborate with Eli Lilly on a phase 2 trial of azelaprag and tirzepatide in people with obesity. In February 2024, it closed a $170 million fundraising round to help support the trial, which is expected to kick off in mid-2024.
The advantage: Azelaprag is administered orally, so taking it alongside a GLP-1 agonist wouldn’t be much of a burden for patients.
The limitation: Though the bed rest trial and animal experiment results are promising, we won’t actually know whether azelaprag can prevent muscle loss due to medication (and not inactivity) until we start seeing the results of this new trial.
What they’re saying: “Our oral drug azelaprag, combined with an incretin drug, has the potential to improve weight loss quantity and quality. Tackling obesity can help cut the population burden of age-related disease.” – BioAge Lab’s CEO Kristen Fortney
Eli Lilly’s other bet
The drug: Versanis Bio’s bimagrumab is a monoclonal antibody, which is a kind of lab-made protein that seeks out and binds to specific receptors. Bimagrumab binds to “activin type II receptors,” which both encourages fat loss and prevents metabolic activity that typically leads to muscle loss.
The details: As of June 2023, bimagrumab had been administered to more than 1,000 people. In one phase 2 trial of people with obesity, some of whom also had type 2 diabetes, participants lost 20.5% of their fat mass while increasing their lean muscle mass by 3.6% over 48 weeks of treatment.
In animal experiments, administering bimagrumab along with a GLP-1 agonist preserved muscle mass while increasing the amount of fat lost. In January 2023, Versanis launched a phase 2b human trial of bimagrumab as an obesity treatment, either alone or co-administered with semaglutide, Novo Nordisk’s GLP-1 agonist. The first results are expected in mid-2024.
In July 2023, Eli Lilly acquired Versanis. If the phase 2b trial goes well, it’s possible the company could trial the combination of bimagrumab and tirzepatide — or another one of the GLP-1 agonists in its pipeline.
The advantage: While people on GLP-1 agonists tend to gain back any weight lost if they stop taking the meds, that might not be the case for bimagrumab — 12 weeks after their last dose, the people in the 1,000-person phase 2 trial had yet to regain any weight.
The limitation: Monoclonal antibodies are expensive to produce, and while bimagrumab only needs to be taken once every four weeks, it needs to be administered intravenously, which has to happen in a medical facility. Most GLP-1 agonists come in injector pens that can be used by patients at home.
What they’re saying: “While the new generation of incretin therapies have been revolutionary for patients living with obesity, bimagrumab addresses a critical unmet need as a therapeutic that targets fat loss while building muscle mass.” – Versanis CEO Mark Pruzanski
The solo act
The drug: Altimmune’s pemvidutide is a combination GLP-1 agonist and glucagon agonist. While the GLP-1 agonist suppresses appetite, the glucagon agonist increases energy expenditure. Together, they are meant to mimic the effects of diet and exercise.
The details: In March 2024, Altimmune announced the results of MOMENTUM, a phase 2 trial in which people received weekly injections of pemvidutide as an obesity treatment.
After 48 weeks, participants lost an average of 15.6% of their weight, and about 75% of the lost weight was fat — a favorable ratio comparable to what’s seen in people who manage to lose weight through improved diet and exercise.
The company plans to present a more detailed analysis of the MOMENTUM trial data at a TBD scientific conference.
The advantage: A single medication that helps people lose weight while also mostly preserving their muscle mass could be preferred over two separate drugs.
The limitation: During the MOMENTUM trial, participants also exercised more, so isolating the drug’s impact is difficult.
What they’re saying: “There is a growing appreciation that the quality of weight loss is as important as the quantity of weight loss … we believe that pemvidutide, if approved, could stand out as an attractive option for weight loss and weight maintenance.” – Altimmune’s CMO Scott Harris
The team effort
The drugs: Regeneron’s trevogrumab and garetosmab are monoclonal antibodies. While trevogrumab binds to and inhibits myostatin, a protein that limits skeletal muscle growth, garetosmab neutralizes a protein called activin A, which is linked to muscle atrophy.
The details: Trevogrumab was developed to treat muscle loss linked to immobility or aging, while garetosmab was created as a treatment for a rare disease where muscle tissue is replaced by bone (called “fibrodysplasia ossificans progressiva”).
In February 2024, Regeneron announced plans to launch a phase 2 trial in mid-2024 that will test combining semaglutide for obesity with either trevogrumab or trevogrumab and garetosmab.
The hope is that the meds will not only prevent excess muscle loss, but potentially help people keep weight off even after they stop taking the GLP-1 agonist.
The advantage: Because Regeneron is targeting two different pathways linked to muscle preservation, its approach could be more impactful than those that target just one.
The limitation: More meds means more opportunities for side effects, and because trevogrumab and garetosmab are monoclonal antibodies, they could be costly and complicated to administer. As is the case with azelaprag, we currently have no idea how these medications will perform in people taking weight-loss drugs, either.
What they’re saying: “We believe that inhibiting new pathways on top of GLP-1 receptor agonism has the potential to achieve comparable overall reductions in body weight, but with improved quality of a weight loss, resulting in more fat loss while preserving or actually increasing muscle mass.” – Regeneron’s CSO George Yancopoulos
The big picture
If any of these medications (or combinations of medications) can actually enable people to lose weight while preserving muscle mass, the impact on public health could be huge — but it’ll likely be years before they reach the market.
In the meantime, people taking GLP-1 agonists for weight loss may need to lean on old fashioned methods for retaining muscle — exercise and a healthy diet — and there are groups trying to make this easier.
Fitness company Equinox has launched the GLP-1 protocol, a coaching program specifically designed to help people on the meds retain and even build muscle. Country club operator Life Time, meanwhile, has launched a new membership program that can help people get prescribed the meds and then build workout routines to accompany them.
Healthcare company Abbott has unveiled a line of high-protein shakes designed to help prevent muscle loss in people taking GLP-1 agonists, and food delivery service Daily Harvest now has a GLP-1 Companion Food collection tailored to people on the meds.
Even if we get to the point that medications alone can help people with obesity lose weight while preserving muscle, being in the “normal” weight range with a good muscle-to-fat ratio doesn’t guarantee good health — as much as we might wish it weren’t true, a better diet and more exercise might still be necessary.
“The fundamentals of obesity management will always be changes to diet and exercise,” said Vijaya Surampudi, assistant director of the UCLA Weight Management Program. “But having anti-obesity medications is another tool in the toolbox.”
I’ve been warning folks that these new weight loss drugs are bad for them.
Good luck with that, your mileage may vary.
Anything that can squeeze Kelly Clarkson on a wide screen TV can’t be all bad
Yes, she’s lost a lot of weight!....................
There are entire websites devoted to celebrities’ “Ozempic face.”
Probably why Gayle King appears sick all the time
My neighbor lost 135 pounds, half her body weight, and looks terrific. I didn’t ask whether she used drugs and I don’t care. She’s probably about 45, has a good job.
“Oprah was taking so much Ozempic that even Gayle lost 12 pounds!”
Katt Williams
The downside is that much of the weight loss is muscle mass. Much of the rebound weight gain returns as fat.
If a doctor has prescribed this stuff without covering the basics, such as the need to maintain and increase muscle mass..they are incompetent. If you go on something like this stuff and don’t do your own research, you are endangering your self.
Too many folks are surprised, and then they rush to lawyers to sue. And we wonder why the cost to bring drugs to market is so high.
I forgot to mention gastric distress and heartburn where there has never been heartburn before.
I’ve seen few pictures. Ghastly looking.
Among others
Everything’s got a catch. I just lost 12 LBS but the catch was pneumonia.
Mounjaro is more effective at weight loss but I suppose has the same problems.
If the Ozempic drops you blood sugar so much as to cause hypoglycemia for a day or two in diabetic persons what must it do for non-diabetics? Woof.
These are the new Carl Sagan drugs since they make Billions and Billions of dollars in profit. They are the statains or the NASIDs of the day.
Back in the days of my youth it was tonsillectomies, they were common, you hardly ever hear of one now. Appendectomies were also quite common. The favorite dental procedure seemed to be the volar flap removal, it just made your teeth get crooked since the flap was meant to provide space for your teeth to grow as you got older. After that, when we got older, most of our wives that could afford it or via insurance got hysterectomies or were medicated with a bunch of estrogen. For a time it was $85,000 back surgeries that were at best 35% effective. And then there is that precautionary colonoscopy. Who can argue with everyone being anesthetized and corn holed for the sake of health safety? After all, what is a little propofol between friends anyway? What other flavor of the day money grubbing medical procedures or drugs can anyone think of?
Today is is type II diabetes or pre-diabetes with people that have an A1C of 6.5 often being read out death sentences and put on hard core regimens including diet and lifestyle coaches.
Please forgive my cynicism. Old age and experience have made me that way.
I got the replay anyway. After lots of blood work and imaging, I have a diagnosis from a biopsy of adenocarcinoma of the ampulla of Vater in the presence of high grade dysplasia. The prescribed fix is a Whipple procedure. Lots of Youtube videos describing it. My surgeon calls it a "kitchen remodel". I appreciate her attempt at humor. She is an exceptionally experienced surgeon in performing Whipple procedures.
SOMEONE CAREFULLY SHOW ME THE “MUSCLE MASS” ON LIZZO.
I missed it.
I've been on it before. The amazing thing about it is that it reduces the "noise" in your head about eating, wanting to eat, when is lunch, I love food, etc.
The magic is what it does to your *desire* to eat ... even if you're hungry. You simply don't want to eat.
The symptoms that I had were very mild. Brief stomach cramping that passed, some mild constipation. As you said, your mileage may vary.
Other than the side effects we don't know about yet, the problem with this drug is that it kills your appetite to the point that you lose weight too quickly ... meaning, your skin doesn't have that slow leisurely time to retract. So unless you are making yourself eat you will have saggy skin and that DOES NOT go away.
Feed cold, starve a fever.......
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