Small open-label study of ATR-258 saw fat loss, lean mass gains and better leg power, but no placebo group and just eight weeks long. <\/p>\n
Losing weight on the new wave of obesity drugs often comes with a side order of lost muscle. Studies suggest that 25\u201345% of the weight lost on incretin-based medicines may be lean mass, according to Atrogi<\/a>, a Swedish biotech that wants to change that.<\/p>\n On 1 October, the Stockholm company announced human data for ATR-258, an oral drug it calls first-in-class. The results are small, early and interesting, in roughly that order of confidence [1<\/a>].<\/p>\n ATR-258 targets a receptor in skeletal muscle called the \u03b22-adrenergic receptor. Older drugs that switch it on, known as \u03b22-agonists, can boost muscle power but come with trade-offs, according to the study\u2019s lead investigator. ATR-258 is \u201cGRK2-biased,\u201d which in simple terms means it is designed to push the receptor down one signaling route inside the cell and leave the others quieter. The hope is muscle benefits without the downsides.<\/p>\n Professor Morten Hostrup, who led the trial, has spent years studying this receptor. \u201cWhat struck me most was the magnitude of the signal in lower-extremity power,\u201d he said. \u201cHaving worked extensively with classical \u03b22-agonists, I know they can enhance power, but not to the extent we observed here.\u201d<\/p>\n 13 is lucky for some <\/p>\n The trial ran eight weeks and enrolled 13 overweight or obese people. It was investigator-initiated, open-label and single-arm, so everybody got the drug, everybody knew it, and there was no placebo group for comparison. Participants stepped through three ascending dose levels, and the drug was well tolerated.<\/p>\n Lower-extremity muscle power improved by about 13% from baseline. Mean fat mass fell by 1.1 kg (about 2.4 pounds) and lean mass rose by 0.8 kg (about 1.8 pounds), both statistically significant. Those changes are modest in absolute terms. The company\u2019s emphasis is on the combination of less fat, more muscle and a stronger body, all at once.<\/p>\n Without a control group, though, it\u2019s hard to say how much of the change came from the drug. Eight weeks and 13 people is a short, small window. Atrogi calls the result first human proof-of-mechanism, a fair description for a study of this kind, and Hostrup himself calls it \u201ca genuinely intriguing signal.\u201d<\/p>\n What comes next <\/p>\n