Pfizer will not advance clinical trials of twice-daily danuglipron formulation, as nearly three in four participants experienced side effects.
Danuglipron, administered as a tablet, is an experimental drug intended to keep blood sugar at healthy levels in patients with type 2 diabetes and obesity. It also slows down the digestion of food, increasing the feeling of fullness after eating.
The medication belongs to a novel class of drugs called GLP-1 agonists, which also include popular type 2 diabetes and weight loss drugs Ozempic, Wegovy, and Saxenda.
In the Phase 2b clinical trial, twice-daily danuglipron led to body weight reductions ranging from 6.9% to 11.7% at 32 weeks, compared to the average gain weight of 1.4% in the placebo group.
However, high rates of mild and gastrointestinal side effects were observed, with up to 73% of the participants experiencing nausea, 47% vomiting, and 25% diarrhea.
More than half of the participants on danuglipron discontinued the medication, compared to approximately 40% with the placebo.
Future development of danuglipron will be focused on a once-daily formulation. The first data is expected in the first half of 2024.
"We believe an improved once-daily formulation of danuglipron could play an important role in the obesity treatment paradigm, and we will focus our efforts on gathering the data to understand its potential profile," said Mikael Dolsten, M.D., Ph.D., Chief Scientific Officer & President, Pfizer Research and Development.
Results from the Phase 2 study previously published in JAMA Network showed that danuglipron reduced HbA1c and fasting plasma glucose in patients with type 2 diabetes. Additionally, it helped to reduce body weight by 4.17 kg (9.1 lbs) on average over 16 weeks.
Concern over side effects
GLP-1 agonists, primarily diabetes drugs increasingly used off-label for weight loss, have skyrocketed in popularity, reaching 40 million prescriptions in the United States last year.
Zepbound (tirzepatide) is the latest GLP-1 agonist approved by the U.S. Food and Drug Administration in November. In clinical trials, Zepbound led to a reduction in body weight by up to 18% in patients without diabetes.
At the same time, there is a growing concern about possible severe side effects. A recent study linked the use of these GLP-1 agonists to an increased risk of pancreatitis, bowel obstruction, and stomach paralysis.
But as type 2 diabetes and obesity are on the rise in the U.S., so is the demand for GLP-1 agonists.