Shedding fat without losing muscle is next weight-loss target for pharma giant

Pharmaceutical giant Eli Lilly will study its blockbuster diabetes drug Mounjaro in combination with an experimental muscle-loss treatment as it searches for ways to help patients maintain muscle while losing weight.

The sheer amount of weight patients are shedding from Mounjaro and similar GLP-1 medications, such as Novo Nordisk’s hit obesity drug semaglutide (the active ingredient in Ozempic and Wegovy), has raised concern that it isn’t just fat melting away, but potentially vital muscle and bone that play key roles in regulating metabolism and preventing injury, particularly in older adults.

Mounjaro is still under regulatory consideration for treating obesity, and many doctors already prescribe it for that purpose. The drug is part of a new generation of therapies that Goldman Sachs analysts have said are poised for a $US100 billion ($160 billion) market by 2030.

Muscle-mass preservation is becoming a hot new area in obesity medicine. Ania Jastreboff, director of the Yale Obesity Research Centre who has led key Mounjaro studies for Lilly, said at a conference that improving the quality — not just the quantity — of weight loss was an essential next-step.

Some muscle loss is expected when a person loses weight. Normally, about a quarter of the weight lost comes from lean mass. That’s a problem for anyone shedding kilos, but potentially dangerous for seniors for whom a decline in muscle and bone can reduce mobility and strength and accelerate frailty.

Experts aren’t clear on just how big of a problem this is for older people taking diabetes and weight-loss drugs such as Mounjaro and Wegovy. In a clinical trial of semaglutide, researchers found that on average, people lost about 6.8 kilograms of lean muscle and 10.4 kilograms of fat during a 68-week trial. The average age in that group of people was 52.

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Lilly’s clinical development arm, Chorus, will run a trial with BioAge Labs, a California biotechnology company whose experimental drug azelaprag has shown early promise in preventing muscle atrophy in older adults who’ve been on bed rest. Lilly and BioAge will test the combination in a mid-stage study starting in mid-2024. They will also assess whether patients lose more weight than with Mounjaro alone.

BioAge’s drug mimics the action of apelin, a hormone produced during exercise that enhances metabolism and muscle function, but decreases with age. Amgen initially developed the drug for heart failure, but abandoned it after it failed an early trial. BioAge, however, saw azelaprag’s promise in another area – ageing.