EASD 2022: Once-Daily Oral Small Molecule GLP-1R Agonist PF-07081532 Robustly Reduces Glucose and Body Weight Within 4-6 Weeks in Adults with Type 2 Diabetes and Non-Diabetic Adults with Obesity

The present abstract evaluates the safety, tolerability, pharmacokinetics and pharmacodynamics of PF-07081532, a small molecule glucagon-like peptide-1 receptor (GLP-1R) agonist administered for 28 or 42 days in adults with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin, and in non-diabetic adults with obesity.

Fifty-one subjects with T2DM were given PF-07081532 once-daily for 28 or 42 days, and 15 participants with obesity were given PF-07081532 once-daily for 42 days. The subjects were randomised to PF-07081532 or placebo in a 4:1 ratio. It was observed that the modelled mean reductions in mean daily glucose in participants with T2DM ranged up to 91 mg/dL over 28 days and 99 mg/dL over 42 days, compared with 29 mg/dL with placebo. 

Fasting plasma glucose decreased up to 79 mg/dL over 28 days and 102 mg/dL over 42 days. In patients with T2DM, body weight reduction ranged up to 5 kg over 28 to 42 days as compared to 2 kg with placebo (mean baseline body weight-T2DM: 90kg, obese participants without diabetes: 98kg) with a similar magnitude of decrease in participants with non-diabetic obesity.

Most adverse events were mild in nature and were consistent with the mechanism of action. 

It is evident from the above results that once-daily oral administration of PF-07081532 has meaningful reductions in plasma glucose and body weight and has a favourable safety and tolerability profile   consistent with the GLP-1R agonist class.