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With the new generation of diabetes drugs becoming a rage owing to their weight-loss properties, the shares of the pharmaceutical giant Pfizer took a tumble on Friday after the company announced that it was not proceeding to a phase 3 trial for its twice-daily regimen of a similar drug. The reason for its decision was the high rates of adverse events such as nausea, vomiting, and diarrhoea leading to nearly half the participants discontinuing the medication.
At least two medicines targeting GLP-1 receptors — Novo Nordisk’s semaglutide and Eli Lilly’s Tirzepatide — have already been approved for weight management.
“At this time, twice-daily danuglipron formulation will not advance into Phase 3 studies,” the company said in a release on Friday, announcing the results of its trial of the twice-daily regimen at 32 weeks.
While this category of weight loss drugs is known to cause gastrointestinal symptoms such as nausea, vomiting, and diarrhoea — and more severe ones such as stomach paralysis — the rates with Pfizer’s danuglipron were higher. Pfizer’s statement said that at 32 weeks, up to 73% experienced nausea, 47% vomiting, and 25% diarrhoea.
The statement added that the rate of discontinuation was also higher, with more than half the participants across all the doses administered stopped the therapy. To compare, nearly 40% of those who were being given the placebo discontinued.
While there were higher rates of adverse effects associated with the medicine, the drug did what it was — bring down the body weight of obese individuals and reduce blood glucose levels of those who had diabetes. The company said that the twice-daily regimen of danuglipron reduced body weight significantly — between 6.9% and 11.7% at 32 weeks.
While these results are yet to be published, the company said that all its future development activities for danuglipron will focus on a one-daily regimen that is likely to be more tolerable. “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, Chief Scientific Officer and President of Pfizer Research and Development.
The company said that the initial data for this is anticipated in the first half of 2024.
An analysis of the medicine at 16 weeks was published in the journal JAMA earlier this year. The study found that 31% to 61% of the participants given different doses of the medicine were able to control their HbA1c levels — the three-month average blood glucose levels. When it comes to weight-loss, however, significant changes were seen only in the groups receiving the two highest doses of the medicine. At 16 weeks, 22% of the participants given the second-highest dose of 80 mg and 47% given the highest dose of 120 mg were able to shed 5% of their body weight.
The rate of adverse events recorded at 16 weeks was similar to what was seen in phase 2 trials for the other drug from the same category Semaglutide as per the study.
Danuglipron belongs to a category of diabetes medicine called GLP-1 receptor agonist. These medicines bring down the blood sugar levels by increasing the secretion of insulin and lowering the secretion of glucagon. Both hormones together ensure a delicate balance of blood glucose levels by increasing its uptake in the cells and reducing its production. The GLP-1 receptor agonists also work by slowing down digestion of food and increasing the feeling of being full after eating.
Danuglipron is an oral formulation. Tirzepatide is available only as a once-weekly injection while Semaglutide is available in oral as well as injectable formulation.
While they were meant as powerful anti-diabetes drug, their significant weight loss property has made them extremely popular, with celebrities such as Elon Musk publicly stating their use of the medicine. With the drugs being extremely efficient in reducing weight for obese individuals, many doctors also believe that they might replace bariatric surgeries in the future.
When it comes to Tirzepatide, participants lost 16% of their body weight on 5mg, 21.4% on 10mg, and 22.5% on 15mg at 72 weeks. Almost 96% of the people on the two higher doses of the medicine achieved at least 5% reduction in their body weight, trials have found.
Semaglutide has been shown to reduce weight by 15% in overweight or obese individuals, with a third of the study participants losing up to 20% of their body weight. Semaglutide is available as Ozempic (injectable) and Rybelsus (oral) for the treatment of type-2 diabetes. The medicine is available as Wegovy in a higher 2.4mg once-a-week injectable dosage for weight loss.
