Roche reported its oral GLP-1 agonist led to an average 6.1% weight loss at four weeks, according to preliminary results from part of a Phase 1 study. The small molecule comes from Roche’s $2.7 billion acquisition of Carmot Therapeutics last year.

By Frank VinluanRoche is a relative latecomer to GLP-1 metabolic disorder drugs, but an oral drug candidate that came as part of a $2.7 billion acquisition last year now has preliminary early-stage clinical data that keep the pharmaceutical giant in contention to bring patients a pill to tap into this increasingly popular mechanism for weight loss.
The results reported Wednesday are from a Phase 1 test of CT-996, a once-daily pill designed to activate the GLP-1 receptor to treat type 2 diabetes and obesity. Roche said treatment of patients who are obese and do not have type 2 diabetes lost a placebo-adjusted average of 6.1% of body weight within four weeks. While that weight loss is greater than four-week results reported by other companies developing oral GLP-1 drugs, the caveat here is it’s a small study and it’s unclear how many patients were included to yield the reported result. Roche said the full study data will be presented at an upcoming medical meeting.
The Phase 1 study is comprised of three parts, two of which have been completed. Part 1 evaluated a single ascending dose in 40 participants who are overweight or obese. Part 2 tested a multiple ascending dose in three sequential groups of 25 total participants with obesity but without type 2 diabetes. Part 3, which will tests CT-996 in two sequential groups of 30 participants with obesity and type 2 diabetes, is on track to begin in the fourth quarter of this year.
CT-996 comes from the labs of Carmot Therapeutics, which Roche purchased last year. Carmot was pursuing the same metabolic targets as other companies, but it aimed to stand out with technology that could improve both efficacy and tolerability. The Carmot platform technology designs drugs that offer “biased signaling,” in which pathways desirable for a drug are emphasized while pathways that lead to undesirable properties are de-emphasized.
Gastrointestinal problems are a known side effect of the GLP-1 agonist drug class, which includes Novo Nordisk’s Wegovy and Eli Lilly’s Zepbound. Roche said CT-996 was well tolerated and the gastrointestinal-related problems were classified as mostly mild or moderate. No unexpected safety signals were reported and no patients discontinued the study drug. Roche also said results showed that taking CT-996 during fasting or after a high-fat meal did not affect blood levels of the drug. Consequently, the drug could be dosed without regard to meal timing, which would give patients greater dosing flexibility. Based on the study data, Roche said it expects CT-996 would be used not only for blood sugar control and inducing weight loss, but also as a potential weight maintenance treatment following weight loss from injectable GLP-1 drugs.
The Carmot acquisition also brought injectable metabolic disorder drugs. The most advanced of them, CT-388, is designed to activate the GLP-1 and GIP receptors, offering the same mechanism of action as Eli Lilly’s tirzepatide. However, the biased signaling of CT-388 is intended to prolong the drug’s pharmacological activity. In preliminary Phase 1b results reported in May, Roche said this once-weekly injectable medication led to placebo-adjusted 18.8% weight loss after 24 weeks.
Companies developing oral small molecules that target GLP-1 drugs include Structure Therapeutics, Terns Pharmaceuticals, and Eli Lilly. Pfizer, which has had some setbacks to its obesity drug research, last week said it had selected for dose optimization a version of once-daily oral drug danuglipron. This move that follows the 2023 termination of small molecule lotiglipron, which had shown signs of liver toxicity. Viking Therapeutics is developing an oral peptide drug to target GLP-1.
In a note sent to investors, William Blair analyst Andy Hsieh acknowledged that the weight loss achieved by patients taking Roche’s drug is one of the highest for oral drugs in development, both peptides and small molecules. But he cautioned that these results come at an early time point in the study and are from a small sample size. It’s premature to call Roche the winner, he added.
“In obesity, the final arbiter will likely be when and where the weight loss plateaus, the tolerability profile, and for small molecules specifically, whether there is a liver toxicity signal,” Hsieh said, referring to the liver signals observed with Pfizer’s lotiglipron.
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