There are only two ways to lose weight. Eat less or burn more. Everything currently on the market does the first, and it's not ideal.
The trouble with eating less is that your body isn't fussy about where it makes the savings. Some of what comes off is fat, some of it is muscle. A fine trade at forty and a considerably worse one at eighty.
So a team at Berkeley went looking the other way and found what they were looking for in the recycling bin. TOFA was made in the 1970s, tried, found wanting and forgotten. What nobody noticed at the time is that it does two things rather than one. It turns down the mechanisms that build fat and turns on the genes that burn it. When given to mice they used up to 18% more energy without moving any more than usual. They just ran hotter, metabolically speaking.
Anyone who knows what happened last time should be shifting in their seat about now. Burning more energy at rest was tried before in the 1930s. It worked exactly as promised, and also cooked people to death. So the detail that matters here is that the mice never got warmer.
Everything else went the right way too. Blood sugar, insulin sensitivity, and muscle left alone. And given alongside other GLP 1s, TOFA didn't compete with them but rather stacked on top. The authors call it complementary rather than a replacement, which could be an honest scientific reading or a commercially convenient one.
The before…
🧐 What's in it for me? These are mice, you are not, so temper excitement. But muscle loss is the elephant in the room for obesity medicine and this is the first serious attempt to solve it by attacking from the opposite direction. If it survives human trials, expect GDP level impact.
💵 Out of the Lab: The appetite suppression market is enormous and well claimed. The muscle preservation market is enormous and very much not.
ReRx Therapeutics, the Berkeley spinout founded to develop TOFA, has one of its own listed as a co-author on the paper, which tells you both how early this is and how committed they are.
Scholar Rock is the listed bet on the same problem, with a drug designed to preserve lean mass in patients on GLP-1s.
Eli Lilly bought its way into muscle preservation in 2023 and has the most to protect if the standard of care becomes a combination rather than a single injection.
Novo Nordisk is in the same race with rather more urgency, having spent two years being overtaken in a market it invented.
Until next time.
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