GLORY-1 (mazdutide high-dose)
Trial question
What is the role of mazdutide in patients with obesity or overweight?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
51.0% female
49.0% male
N = 407
407 patients (209 female, 198 male).
Inclusion criteria: adult patients, aged 18-75 years, with obesity or overweight.
Key exclusion criteria: HbA1c ≥ 6.5% at screening or previous diagnosis of T1DM or T2DM; weight change > 5.0% after diet and exercise control for at least 12 weeks before screening; receipt of weight loss drugs in the past 3 months; history of pancreatitis; family or personal history of medullary thyroid cancer or multiple endocrine neoplasia 2A or 2B; moderate-to-severe depression or severe mental illness; lifetime history of suicide attempt.
Interventions
N=202 mazdutide (dose adjusted to a maximum of 6 mg once weekly for 48 weeks).
N=205 placebo (matching placebo for 48 weeks).
Primary outcome
Least-squares mean reduction in body weight at week 32
12.55%
-0.45%
12.6 %
9.4 %
6.3 %
3.1 %
0.0 %
-3.1 %
Mazdutide
Placebo
Significant
increase ▲
NNT = 7
Significantly greater reduction in least-squares mean body weight at week 32 (12.55% vs. -0.45%; MD 13, 95% CI 11.7 to 14.31).
Secondary outcomes
Significant increase in the percentage of patients achieving a weight reduction of ≥ 5% at week 32 (82% vs. 10.5%; RR 7.9, 95% CI 5.1 to 12.2).
Significantly greater reduction in least-squares mean body weight at week 48 (14.01% vs. -0.3%; MD 14.31, 95% CI 12.74 to 15.88).
Significantly greater reduction in waist circumference at week 48 (10.72 cm vs. 1.41 cm; MD 9.31, 95% CI 8.08 to 10.54).
Safety outcomes
No significant difference in serious adverse events.
Conclusion
In adult patients, aged 18-75 years, with obesity or overweight, mazdutide was superior to placebo with respect to a least-squares mean reduction in body weight at week 32.
Reference
Linong Ji, Hongwei Jiang, Yan Bi et al. Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight. N Engl J Med. 2025 May 25. Online ahead of print.
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