Mazdutide superior to dulaglutide for reducing HbA1c, body weight in type 2 diabetes
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Key takeaways:
- Adults with type 2 diabetes had larger decreases in HbA1c at 28 weeks with mazdutide vs. dulaglutide.
- More than half of patients assigned mazdutide lost at least 5% of their body weight.
A once-weekly GLP-1/glucagon dual agonist conferred greater decreases in HbA1c and body weight than the GLP-1 receptor agonist dulaglutide for adults with type 2 diabetes, according to a presenter.
As Healio previously reported, mazdutide (Eli Lilly/Innovent) is one of several GLP-1/glucagon dual agonists currently being investigated for the treatment of type 2 diabetes and obesity.
In a past phase 2 trial of Chinese patients with type 2 diabetes, “mazdutide dosed up to 6 mg for 20 weeks demonstrating meaningful glycemic control, dose-dependent weight reductions and improvements on multiple cardiometabolic risk factors,” Lixin Guo, MD, PhD, professor in the department of endocrinology at Beijing Hospital in China, said during a presentation at the European Association for the Study of Diabetes annual meeting.
Guo presented results of the phase 3 DREAMS-2 randomized controlled trial, which compared 4 mg and 6 mg mazdutide with dulaglutide (Trulicity, Eli Lilly).
Researchers enrolled 731 adults aged 18 years and older with type 2 diabetes and an HbA1c between 7.5% and 11% 2 months before screening despite stable metformin therapy and with or without the use of SGLT2 inhibitors or sulfonylureas (mean age, 51.8 years; mean baseline HbA1c, 8.22%; mean baseline body weight, 76.95 kg; mean baseline BMI, 27.91 kg/m2). Participants were randomly assigned to receive 4 mg mazdutide, 6 mg mazdutide or 1.5 mg dulaglutide once-weekly for 28 weeks. The primary endpoint was noninferiority in mean HbA1c change from baseline to 28 weeks between the mazdutide groups and dulaglutide group. Researchers also assessed change in fasting plasma glucose and body weight.
Mazdutide outperforms dulaglutide
In the treatment policy estimand, from baseline to 28 weeks, the 4 mg mazdutide group had a 1.61 percentage point reduction in HbA1c and the 6 mg mazdutide group had a 1.66 percentage point decrease, compared with a 1.36 percentage point decline for adults receiving dulaglutide (P for superiority < .01 for both). A greater proportion of adults receiving 6 mg mazdutide achieved an HbA1c of less than 7% at 28 weeks than those receiving dulaglutide (70.4% vs. 61.6%; P for superiority < .05). The proportion of adults achieving an HbA1c of less than 6.5% at 28 weeks was higher in the 4 mg mazdutide group (52%) and the 6 mg mazdutide group (59.9%) than the dulaglutide group (41.6%; P < .05 vs. 4 mg mazdutide; P < .0001 vs. 6 mg mazdutide).
Adults receiving 6 mg mazdutide had a 37.1 mg/dL decrease in fasting plasma glucose from baseline to 28 weeks compared with a 30.6 mg/dL reduction for the dulaglutide group (P < .05).
The percentage body weight change from baseline to 28 weeks was greater for the 4 mg mazdutide group (mean change, –8.53%) and the 6 mg mazdutide group (mean change, –6.55%) than those receiving dulaglutide (mean change, –2.77%; P for superiority < .0001 for both). At 28 weeks, 73.1% of the 6 mg mazdutide group and 58.6% of the 4 mg mazdutide group lost at least 5% of their body weight compared with 26.6% of those in the dulaglutide group (P < .0001). The proportion of adults achieving a weight loss of 5% or greater and an HbA1c of less than 7% at 28 weeks was 59.9% with 6 mg mazdutide, 46.9% with 4 mg mazdutide and 18.9% with dulaglutide (P for superiority < .0001 for both).
“The results support the use of mazdutide as an add-on to oral anti-diabetes drugs for the treatment of type 2 diabetes,” Guo said.
Gastrointestinal events with mazdutide
Serious treatment-emergent adverse events were reported by 5.8% of participants receiving 4 mg mazdutide, 4.9% of those in the 6 mg mazdutide group and 7.8% of adults receiving 1.5 mg dulaglutide. There were five adverse events leading to treatment discontinuation with 4 mg mazdutide, nine with 6 mg mazdutide, and four with dulaglutide.
“The main side effects reported were gastrointestinal adverse events, including diarrhea, nausea and vomiting,” Guo said.
Reports of gastrointestinal events were more frequent in both mazdutide groups compared with dulaglutide. The percentage of adults reporting diarrhea was 36.8% with 4 mg mazdutide and 34.8% with 6 mg mazdutide vs. 22.4% with dulaglutide. Nausea was reported by 35.5% of adults receiving 4 mg mazdutide and 34.4% of those receiving 6 mg mazdutide vs. 17.1% of the dulaglutide group.
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Guo L, et al. LBA 16. Presented at: European Association for the Study of Diabetes Annual Meeting; Sept. 9-13, 2024; Madrid, Spain.
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