Pfizer's Investigational Oral GLP-1R Agonist PF-06882961 Shows Promising Early Results in Reducing Weight and Glucose in Type 2 Diabetes Patients

Compiled by Keke

Recently, at the American Diabetes Association (ADA) virtual meeting, Pfizer presented Phase 1 clinical study data evaluating PF-06882961, an oral small-molecule glucagon-like peptide-1 receptor (GLP-1R) agonist for patients with type 2 diabetes mellitus (T2DM). The results demonstrated that PF-06882961 significantly reduced glucose levels and body weight in patients.

It is reported that this is a randomized, double-blind, placebo-controlled, multiple-ascending-dose Phase 1 clinical study designed to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PF-06882961 in patients with type 2 diabetes mellitus (T2DM) over a 28-day treatment period. The study randomized 98 T2DM patients who were taking metformin into eight cohorts (five planned and three backup) in a 3:1 ratio to receive either PF-06882961 (twice daily, up to a maximum dose of 120 mg) or placebo for 28 days. Of these, 92 patients completed the inpatient portion of the study. Fasting plasma glucose (FPG), 24-hour mean daily glucose (MDG), and body weight were assessed at baseline and on Day 28.

The results showed that fasting plasma glucose (FPG), mean daily glucose (MDG), and body weight were significantly reduced in adult patients with type 2 diabetes mellitus (T2DM) on Day 28. Improvements were observed at all dose levels, with the greatest improvements seen in the 120 mg dose group: mean body weight decreased by approximately 18 pounds, FPG decreased by 89.7 mg/dL, and MDG decreased by 105.9 mg/dL.

Furthermore, multiple oral doses of PF-06882961 demonstrated favorable safety and tolerability in adult patients with type 2 diabetes. Most adverse events were mild, including nausea, dyspepsia, diarrhea, headache, and constipation.

Previous laboratory studies in animals have shown that PF-06882961 (3–240 mg daily) causes mild to moderate cardiac damage and moderate to severe effects on the thymus (which plays a role in controlling infections). Administration of the highest dose in rats resulted in moderate gastric ulcers.

Molecular Structure of PF-06882961 (Source: MedChemExpress Website)

Pfizer particularly emphasized the results showing that this experimental drug can reduce patients’ body weight. The company stated, “These data provide certain signs of weight loss observed for the GLP-1 receptor agonist PF-06882961 in Phase I studies, which can be said to be more effective than any approved GLP-1 class medication currently on the market.”

In the United States alone, type 2 diabetes affects more than 28 million people. Despite available treatment options, many patients still achieve suboptimal glycemic control. Glucagon-like peptide-1 (GLP-1) receptor agonists are a commonly used therapeutic option for patients with diabetes, helping to lower blood glucose levels, including glycated hemoglobin A1c (HbA1c), and aiding in weight reduction.

PF-06882961 is an oral small-molecule GLP-1 receptor (GLP-1R) agonist whose efficacy has been demonstrated in nonclinical models to be comparable to that of injectable peptide GLP-1R agonists. Most currently available GLP-1 therapies are injectable agents, a class first introduced to the market in 2005. It was not until 2019, with the approval of Novo Nordisk’s Rybelsus (semaglutide), that the first oral GLP-1 receptor agonist for the treatment of type 2 diabetes became available. Consequently, Pfizer believes that PF-06882961 has the potential to bring welcome advancements to the management of diabetes.

Reference source: Study: Pfizer's Experimental Diabetes Drug Robustly Reduces Weight and Glucose