GLP-1/glucagon dual agonist reduces weight across three dosing regimens in obesity

Key takeaways:

• Mazdutide conferred weight loss of 18.1% at 32 weeks and 22.3% at 48 weeks with a 16 mg dose.
• Gastrointestinal adverse events occurred more frequently for adults receiving higher doses of mazdutide.

ATLANTA — A GLP-1/glucagon dual agonist induced significant weight loss and improved multiple cardiometabolic parameters for adults with overweight or obesity, according to phase 2 data presented at ObesityWeek.

As Healio previously reported, mazdutide (Eli Lilly/Innovent), a once-weekly injectable GLP-1/glucagon dual agonist developed for the treatment of obesity, conferred a weight reduction of 12.55% with a 6 mg dose among adults with overweight or obesity in the phase 3 GLORY-1 trial conducted in China. In new findings from a phase 2 dose-finding study, the investigational drug was tied to a weight loss of up to 22.3% with a 16 mg dose.

“Overall, we believe that these data show that mazdutide is effective in producing weight loss across all of the doses studied,” Stanley H. Hsia, MD, FRCPC, FACE, a principal investigator for Velocity Clinical Research in Huntington Beach, California, said during a presentation.

Researchers enrolled 177 adults aged 18 years and older with obesity or overweight plus one of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea or cardiovascular disease. Participants were randomly assigned to 6 mg, 10 mg or 16 mg mazdutide or placebo for 48 weeks. Each of the mazdutide groups began with a once-weekly 1.5 mg dose and titrated up to their final dosage. The primary endpoint was change in body weight from baseline to 32 weeks. Change in body weight at 48 weeks was assessed as a secondary endpoint.

Study outcomes

At 32 weeks, the reduction in body weight with mazdutide was 7.3% with a 6 mg dose, 15.6% with the 10 mg dose and 18.1% with the 16 mg dose vs. a 0.9% weight reduction with placebo (P < .001). At 48 weeks, weight loss was 10.5% with 6 mg mazdutide, 19.2% with 10 mg of the study drug, and 22.3% with the 16 mg dose vs. no weight change with placebo (P < .001 for all).

“All of these mazdutide treatment curves did not seem to plateau, suggesting that had we continued treatment beyond 48 weeks, greater degrees of weight loss might actually have been seen,” Hsia said.

At 48 weeks, 52% of the 16 mg mazdutide group and 49% of the 10 mg group lost at least 20% of their body weight compared with 3% of the placebo group (P < .001 for both). A weight loss of at least 25% was achieved by 35% of the 16 mg mazdutide group (P < .001) and 29% of adults receiving 10 mg of the study drug (P < .01) vs. 3% of placebo at 48 weeks.

At 48 weeks, waist circumference decreased by 11 cm in the 6 mg mazdutide group, 16.7 cm in the 10 mg group and 16.6 cm with the 16 mg dose vs. a 1.2 cm reduction with placebo (P < .001 for all).

All three mazdutide groups had significant decreases in HbA1c, fasting glucose and fasting insulin at 48 weeks compared with placebo. The 10 mg and 16 mg mazdutide groups also had significant declines in LDL cholesterol, non-HDL cholesterol and triglycerides vs. placebo.

Safety data

Treatment-emergent adverse events related to the study drug occurred among 78.1% of the 6 mg mazdutide group, 76.6% of the 10 mg group and 82.4% of the 16 mg group vs. 53.2% of the placebo group. Two adults in the 16 mg mazdutide group and one participant in each of the other two mazdutide groups and the placebo group experienced a serious adverse event. No deaths occurred during the trial.

The most common treatment-emergent adverse events were gastrointestinal in nature, with most being mild to moderate in severity.

“There did appear to be a subtle imbalance in the incidence of gastrointestinal side effects between the mazdutide 16 mg group and the 10 mg group,” Hsia said. “This became evident with respect to nausea, with respect to vomiting and with respect to discontinuation of treatment due to these side effects.”

There were also mean increases in heart rate of less than 10 bpm in all three mazdutide groups, with greater increases found with higher doses. There were no cases of pancreatitis, retinopathy, C-cell hyperplasia or thyroid malignancies reported during the study, Hsia said.

‘);
notification.css({
‘position’: ‘fixed’,
‘top’: ’20px’,
‘right’: ’20px’,
‘background’: ‘#373D3F’,
‘color’: ‘white’,
‘padding’: ’10px 15px’,
‘border-radius’: ‘5px’,
‘z-index’: ‘9999’,
‘font-size’: ’14px’,
‘box-shadow’: ‘0 2px 8px rgba(0,0,0,0.2)’
});

$(‘body’).append(notification);

// Fade out and remove after 3 seconds
setTimeout(function () {
notification.fadeOut(300, function () {
notification.remove();
});
}, 3000);
}
//# sourceURL=social.js