A novel glucagon-like peptide-1 (GLP-1)/glucagon dual receptor agonist, BI 456906, being developed by Boehringer Ingelheim and Zealand Pharma led to “impressive” weight loss in a phase 2 dosing study of patients with overweight/obesity and type 2 diabetes – but this is early research.
Julio Rosenstock, MD, presented the study results, including weight loss and adverse events, during an oral session at ObesityWeek® 2022.
At the highest tested dose (1.8 mg twice weekly subcutaneous injections), 57% of patients lost at least 5% of their initial body weight and 35% lost at least 10% of their initial body weight at 16 weeks.
In contrast, among the patients who received a 1-mg semaglutide dose as a comparator, 38% lost at least 5% of their initial body weight and 16% lost at least 10% of their initial body weight at study end.
This is “very promising data as an anti-obesity compound,” said Rosenstock, professor of medicine, University of Texas Southwestern Medical Center in Dallas.
The researchers enrolled 411 adults and randomized them into eight groups of roughly 50 patients each.
They compared six doses of BI 456906 (from 0.3 mg/week to 1.8 mg twice weekly) versus 1 mg/week of the GLP-1 agonist semaglutide (Wegovy, Novo Nordisk) versus placebo.
Patients had a mean initial weight of 97 kg (214 pounds).
After 4 months, on average, patients who received the highest tested dose of BI 456906 lost 9% of their initial weight or roughly 8.7 kg (19 pounds).
Patients who received semaglutide lost 5.4% of their initial weight or roughly 5.2 kg (11.5 pounds), and patients who received placebo lost only 1.2% of their initial weight
The main adverse events were gastrointestinal.
“Exciting Data,” But Still Early Days
“This is very exciting data. It comes from another experienced company with a track record of successful products with a new compound in a class where other related compounds have shown efficacy and safety,” Dan Bessesen, MD, president of The Obesity Society, who was not involved with this research, told Medscape Medical News in an email.
“The degree of weight loss is impressive for a 16-week study,” Bessesen, professor of medicine in the Division of Endocrinology, Metabolism and Diabetes at the University of Colorado, added. “The longer-term weight loss will likely be more.”
The side-effect profile is not particularly concerning and is like other drugs in this general class, he said.
However, he also noted a few caveats. This was only a phase 2 study, “so we should not make firm conclusions about efficacy from a study like this, as the number of subjects studied at each dose is relatively small and the follow up not long.”
In addition, “the dose of semaglutide is the old ‘diabetes’ dose (1 mg) not the weight-loss dose of 2.4 mg or the new diabetes dose of 2 mg. It is not a real comparison with the maximal approved dose of semaglutide. So, we cannot say that it will be better than semaglutide.”
The next hurdle is the “need to see phase 3 studies in a larger group of patients studied for a longer time. Then [the company] will need FDA approval, so it may be a bit of time” before this drug potentially enters the marketplace.
The “bottom line” is that this potential new anti-obesity/diabetes drug is “very promising, but [it is] still a little early to say where it ultimately will go.”
A1c Results Presented at EASD
To be included in this study, patients had to be 18 to 75 years old, have type 2 diabetes, a body mass index (BMI) of 25 to 50 kg/m2, and A1c of 7% to 10%, and be stable on metformin therapy.
The patients had a mean age of 57 years and 57% were men. They had a mean A1c of 8.1%, a mean BMI of 34 kg/m2, and a mean waist circumference of 110 cm (43 inches).
“We just recently reported at the EASD conference last month, the effect of BI 456906 on A1c lowering,” Rosenstock said.
“It looks like the [drop in] A1c plateaus at 1.9%, which is pretty good when you consider the baseline A1c is around 8%. You get down to around 6%, which is what we regard as a very robust reduction in people with type 2 diabetes on metformin.”
The current analysis showed that patients who received doses of 0.3, 0.9, 1.8, and 2.7 mg/week of the novel drug lost 1.9%, 4.4%, 6.6%, and 6.7% of their initial body weight, respectively, after 16 weeks.
The patients who received 1.2 mg and 1.8 mg twice weekly lost even more weight, 7.2% and 9% of their initial weight, respectively.
At the highest dose, on average, patients lost 13 cm (5 inches) around their waist.
Adverse events were reported by 78% of the patients, most commonly nausea (34% of patients), vomiting (18%), and diarrhea (16%).
Only 1.3% of patients had a drug-related serious adverse event. A total of 16% of patients discontinued the therapy.
Most of the “gastrointestinal adverse events leading the treatment discontinuation were possibly dose and titration related,” Rosenstock said, “and it’s highly conceivable that for future studies a slower dose escalation may mitigate the occurrence of the gastrointestinal adverse events.”
BI 456906 was co-invented with Zealand Pharma. Under the licensing agreement, Boehringer Ingelheim funds all research, development, and commercialization.
ObesityWeek® 2022. Abstract Oral-063. Presented November 3, 2022.
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