Safety and efficacy of a GLP-1 and glucagon receptor dual agonist mazdutide (IBI362) 9 mg and 10 mg in Chinese adults with overweight or obesity: A randomised, placebo-controlled, multiple-ascending-dose phase 1b trial.

Ji L, Gao L, Jiang H, Yang J, Yu L, Wen J, Cai C, Deng H, Feng L, Song B, Ma Q, Qian L

EClinicalMedicine7 Oct 2022Cited by 66 (Europe PMC)

PMID36247927PMCIDPMC9561728DOI10.1016/j.eclinm.2022.101691PepBankPUB-36247927

Summary

BackgroundMazdutide (also known as IBI362 or LY3305677), a novel once-weekly glucagon-like peptide-1 (GLP-1) and glucagon receptor dual agonist, achieved 12-week body weight loss up to 6.4% at doses up to 6 mg in Chinese adults with overweight or obesity. We further explored the safety and efficacy of mazdutide dosed up to 9 mg and 10 mg.MethodsIn this randomised, placebo-controlled, multiple-ascending-dose phase 1b trial, we enrolled adults (aged 18-75 years, both inclusive) with overweight (body-mass index [BMI] ≥24 kg/m²) accompanied by hyperphagia and/or at least one obesity-related comorbidity or obesity (BMI ≥28 kg/m²) from five hospitals in China. Eligible participants were randomly assigned (2:1) within each cohort by using an interactive web-response system to receive once-weekly subcutaneous mazdutide or placebo for 12 weeks in the 9 mg cohort (3 mg weeks 1-4; 6 mg weeks 5-8; 9 mg weeks 9-12) and for 16 weeks in the 10 mg cohort (2.5 mg weeks 1-4; 5 mg weeks 5-8; 7.5 mg weeks 9-12; 10 mg weeks 13-16). The participants, investigators, study site personnel involved in treating and assessing participants in each cohort and sponsor personnel were masked to treatment allocation. The primary outcomes were safety and tolerability of mazdutide, assessed from baseline to end of follow-up in all participants who received at least one dose of the study treatment. The secondary outcomes included the change from baseline to week 12 or week 16 in body weight, waist circumference and BMI. This trial is registered with ClinicalTrials.gov, NCT04440345.FindingsBetween Mar. 1, 2021 and Mar. 26, 2021, a total of 24 participants were enrolled, with eight randomly assigned to mazdutide and four to placebo in each cohort. One participant receiving mazdutide and two receiving placebo in the 10 mg cohort withdrew consent and quitted the study. No serious adverse event was reported. All treatment-emergent adverse events (TEAEs) were mild or moderate in severity and most commonly-reported TEAEs were upper respiratory tract infection, diarrhoea, decreased appetite, nausea, urinary tract infection, abdominal distension and vomiting. The mean percent change from baseline to week 12 in body weight were -11.7% (SE 1.5) for participants receiving mazdutide in the 9 mg cohort and -1.8% (1.6) for participants receiving placebo (estimated treatment difference [ETD]: -9.8%; 95% confidence interval [CI]: -14.4, -5.3; P = 0.0002). The mean percent change from baseline to week 16 in body weight were -9.5% (SE 1.7) for participants receiving mazdutide in the 10 mg cohort and -3.3% (1.9) for participants receiving placebo (ETD: -6.2%; 95% CI: -11.5, -0.9; P = 0.024). In addition, compared with placebo, mazdutide achieved more profound reductions in waist circumference and BMI.InterpretationMazdutide dosed up to 9 mg and 10 mg was both well tolerated and showed a favourable safety profile. High-dose mazdutide showed promising 12-week body weight loss, holding great potential for the treatment of moderate-to-severe obesity. A larger and longer phase 2 trial will further evaluate the efficacy and safety of high-dose mazdutide in Chinese adults with obesity.FundingInnovent Biologics, Inc.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study8

8 results from studies that gave the peptide. 8 results from people.

01HumanRandomized controlled trialSafety outcome
In Chinese adults with overweight or obesity, no serious adverse event was reported with mazdutide up to 9 mg and 10 mg.
In plain wordsIn Chinese adults with overweight or obesity, no serious side effects were reported with mazdutide at these doses.
Peptide
Mazdutide
Outcome
No significant changeSerious adverse events
Study
n = 24
Comparator
Placebo
Analysis
Primary
Outcome group
Adverse events · Whole body
Studied dose
9 mg and 10 mg cohorts · subcutaneous · 12 to 16 weeksAs given in this study (human).
Source sentences
Summary
No serious adverse event was reported.
3 context sentences(design, population, supporting numbers)
Summary · context
The primary outcomes were safety and tolerability of mazdutide, assessed from baseline to end of follow-up in all participants who received at least one dose of the study treatment.
Summary · context
In this randomised, placebo-controlled, multiple-ascending-dose phase 1b trial, we enrolled adults (aged 18-75 years, both inclusive) with overweight (body-mass index [BMI] ≥24 kg/m²) accompanied by hyperphagia and/or at least one obesity-related comorbidity or obesity (BMI ≥28 kg/m²) from five hospitals in China.
Summary · context
26, 2021, a total of 24 participants were enrolled, with eight randomly assigned to mazdutide and four to placebo in each cohort.
Show in the study text Report a problemFND-3624792705
02HumanRandomized controlled trialSafety outcome
In Chinese adults with overweight or obesity, all treatment-emergent adverse events with mazdutide were mild or moderate in severity.
In plain wordsIn Chinese adults with overweight or obesity, all side effects during mazdutide treatment were mild or moderate.
Peptide
Mazdutide
Outcome
Not applicableSeverity of treatment-emergent adverse events
Study
n = 24
Analysis
Primary
Outcome group
Adverse events · Whole body
Studied dose
9 mg and 10 mg cohorts · subcutaneous · 12 to 16 weeksAs given in this study (human).
Source sentences
Summary
All treatment-emergent adverse events (TEAEs) were mild or moderate in severity
3 context sentences(design, population, supporting numbers)
Summary · context
The primary outcomes were safety and tolerability of mazdutide, assessed from baseline to end of follow-up in all participants who received at least one dose of the study treatment.
Summary · context
In this randomised, placebo-controlled, multiple-ascending-dose phase 1b trial, we enrolled adults (aged 18-75 years, both inclusive) with overweight (body-mass index [BMI] ≥24 kg/m²) accompanied by hyperphagia and/or at least one obesity-related comorbidity or obesity (BMI ≥28 kg/m²) from five hospitals in China.
Summary · context
26, 2021, a total of 24 participants were enrolled, with eight randomly assigned to mazdutide and four to placebo in each cohort.
Show in the study text Report a problemFND-3624792706
03HumanRandomized controlled trialEfficacy outcome
In Chinese adults with overweight or obesity, mazdutide achieved greater reductions in waist circumference than placebo.
In plain wordsIn Chinese adults with overweight or obesity, mazdutide reduced waist size more than placebo.
Peptide
Mazdutide
Outcome
DecreaseWaist circumference change
Study
n = 24
Comparator
Placebo
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
9 mg and 10 mg cohorts · subcutaneous · 12 to 16 weeksAs given in this study (human).
Source sentences
Summary
In addition, compared with placebo, mazdutide achieved more profound reductions in waist circumference and BMI.
3 context sentences(design, population, supporting numbers)
Summary · context
The secondary outcomes included the change from baseline to week 12 or week 16 in body weight, waist circumference and BMI.
Summary · context
In this randomised, placebo-controlled, multiple-ascending-dose phase 1b trial, we enrolled adults (aged 18-75 years, both inclusive) with overweight (body-mass index [BMI] ≥24 kg/m²) accompanied by hyperphagia and/or at least one obesity-related comorbidity or obesity (BMI ≥28 kg/m²) from five hospitals in China.
Summary · context
26, 2021, a total of 24 participants were enrolled, with eight randomly assigned to mazdutide and four to placebo in each cohort.
Show in the study text Report a problemFND-3624792703
04HumanRandomized controlled trialEfficacy outcome
In Chinese adults with overweight or obesity, mazdutide achieved greater reductions in BMI than placebo.
In plain wordsIn Chinese adults with overweight or obesity, mazdutide lowered BMI more than placebo.
Peptide
Mazdutide
Outcome
DecreaseBody mass index change
Study
n = 24
Comparator
Placebo
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
9 mg and 10 mg cohorts · subcutaneous · 12 to 16 weeksAs given in this study (human).
Source sentences
Summary
In addition, compared with placebo, mazdutide achieved more profound reductions in waist circumference and BMI.
3 context sentences(design, population, supporting numbers)
Summary · context
The secondary outcomes included the change from baseline to week 12 or week 16 in body weight, waist circumference and BMI.
Summary · context
In this randomised, placebo-controlled, multiple-ascending-dose phase 1b trial, we enrolled adults (aged 18-75 years, both inclusive) with overweight (body-mass index [BMI] ≥24 kg/m²) accompanied by hyperphagia and/or at least one obesity-related comorbidity or obesity (BMI ≥28 kg/m²) from five hospitals in China.
Summary · context
26, 2021, a total of 24 participants were enrolled, with eight randomly assigned to mazdutide and four to placebo in each cohort.
Show in the study text Report a problemFND-3624792704
05HumanRandomized controlled trialEfficacy outcome
In Chinese adults with overweight or obesity, mazdutide in the 9 mg cohort reduced body weight by 11.7% at week 12, compared with 1.8% with placebo.
In plain wordsIn Chinese adults with overweight or obesity, mazdutide up to 9 mg lowered body weight more than placebo after 12 weeks.
Peptide
Mazdutide
Outcome
DecreaseBody weight percentage change at week 12, 9 mg cohort
Study
n = 12
Comparator
Placebo
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
9 mg (escalation 3 mg, 6 mg, 9 mg) · subcutaneous · 12 weeksAs given in this study (human).
Measurements
Body weight change
−11.7%
mazdutide 9 mg cohort
Body weight change
−1.8%
placebo
Estimated treatment difference
−9.8%
mazdutide 9 mg vs placebo
Source sentences
Summary
The mean percent change from baseline to week 12 in body weight were -11.7% (SE 1.5) for participants receiving mazdutide in the 9 mg cohort and -1.8% (1.6) for participants receiving placebo (estimated treatment difference [ETD]: -9.8%; 95% confidence interval [CI]: -14.4, -5.3; P = 0.0002).
3 context sentences(design, population, supporting numbers)
Summary · context
The secondary outcomes included the change from baseline to week 12 or week 16 in body weight, waist circumference and BMI.
Summary · context
In this randomised, placebo-controlled, multiple-ascending-dose phase 1b trial, we enrolled adults (aged 18-75 years, both inclusive) with overweight (body-mass index [BMI] ≥24 kg/m²) accompanied by hyperphagia and/or at least one obesity-related comorbidity or obesity (BMI ≥28 kg/m²) from five hospitals in China.
Summary · context
26, 2021, a total of 24 participants were enrolled, with eight randomly assigned to mazdutide and four to placebo in each cohort.
Show in the study text Report a problemFND-3624792701
06HumanRandomized controlled trialEfficacy outcome
In Chinese adults with overweight or obesity, mazdutide in the 10 mg cohort reduced body weight by 9.5% at week 16, compared with 3.3% with placebo.
In plain wordsIn Chinese adults with overweight or obesity, mazdutide up to 10 mg lowered body weight more than placebo after 16 weeks.
Peptide
Mazdutide
Outcome
DecreaseBody weight percentage change at week 16, 10 mg cohort
Study
n = 12
Comparator
Placebo
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
10 mg (escalation 2.5 mg, 5 mg, 7.5 mg, 10 mg) · subcutaneous · 16 weeksAs given in this study (human).
Measurements
Body weight change
−9.5%
mazdutide 10 mg cohort
Body weight change
−3.3%
placebo
Estimated treatment difference
−6.2%
mazdutide 10 mg vs placebo
Source sentences
Summary
The mean percent change from baseline to week 16 in body weight were -9.5% (SE 1.7) for participants receiving mazdutide in the 10 mg cohort and -3.3% (1.9) for participants receiving placebo (ETD: -6.2%; 95% CI: -11.5, -0.9; P = 0.024).
3 context sentences(design, population, supporting numbers)
Summary · context
The secondary outcomes included the change from baseline to week 12 or week 16 in body weight, waist circumference and BMI.
Summary · context
In this randomised, placebo-controlled, multiple-ascending-dose phase 1b trial, we enrolled adults (aged 18-75 years, both inclusive) with overweight (body-mass index [BMI] ≥24 kg/m²) accompanied by hyperphagia and/or at least one obesity-related comorbidity or obesity (BMI ≥28 kg/m²) from five hospitals in China.
Summary · context
26, 2021, a total of 24 participants were enrolled, with eight randomly assigned to mazdutide and four to placebo in each cohort.
Show in the study text Report a problemFND-3624792702
07HumanRandomized controlled trialSafety outcome
In Chinese adults with overweight or obesity, the most common adverse events were upper respiratory tract infection, diarrhoea, decreased appetite, nausea, urinary tract infection, abdominal distension and vomiting.
In plain wordsIn Chinese adults with overweight or obesity, common side effects were respiratory infection, diarrhoea, reduced appetite, nausea, urinary infection, bloating and vomiting.
Peptide
Mazdutide
Outcome
Not applicableMost common treatment-emergent adverse events
Study
n = 24
Outcome group
Adverse events · Whole body
Studied dose
9 mg and 10 mg cohorts · subcutaneous · 12 to 16 weeksAs given in this study (human).
Source sentences
Summary
most commonly-reported TEAEs were upper respiratory tract infection, diarrhoea, decreased appetite, nausea, urinary tract infection, abdominal distension and vomiting.
2 context sentences(design, population, supporting numbers)
Summary · context
In this randomised, placebo-controlled, multiple-ascending-dose phase 1b trial, we enrolled adults (aged 18-75 years, both inclusive) with overweight (body-mass index [BMI] ≥24 kg/m²) accompanied by hyperphagia and/or at least one obesity-related comorbidity or obesity (BMI ≥28 kg/m²) from five hospitals in China.
Summary · context
26, 2021, a total of 24 participants were enrolled, with eight randomly assigned to mazdutide and four to placebo in each cohort.
Show in the study text Report a problemFND-3624792707
08HumanRandomized controlled trialSafety outcome
In the 10 mg cohort, one participant receiving mazdutide and two receiving placebo withdrew consent and left the study.
In plain wordsIn the 10 mg group, one person on mazdutide and two on placebo withdrew consent and left the study.
Peptide
Mazdutide
Outcome
Not applicableWithdrawal of consent
Study
n: not reported in source
Comparator
Placebo
Outcome group
Adverse events · Whole body
Studied dose
10 mg cohort · subcutaneous · 16 weeksAs given in this study (human).
Source sentences
Summary
One participant receiving mazdutide and two receiving placebo in the 10 mg cohort withdrew consent and quitted the study.
2 context sentences(design, population, supporting numbers)
Summary · context
In this randomised, placebo-controlled, multiple-ascending-dose phase 1b trial, we enrolled adults (aged 18-75 years, both inclusive) with overweight (body-mass index [BMI] ≥24 kg/m²) accompanied by hyperphagia and/or at least one obesity-related comorbidity or obesity (BMI ≥28 kg/m²) from five hospitals in China.
Summary · context
26, 2021, a total of 24 participants were enrolled, with eight randomly assigned to mazdutide and four to placebo in each cohort.
Show in the study text Report a problemFND-3624792708

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 1/2NCT04440345

Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IBI362 in Overweight or Obesity Subjects

Innovent Biologics (Suzhou) Co. Ltd.n = 6016 Jun 2020 to 6 Aug 2021

Overweight or Obesity

Trial page ClinicalTrials.govUpdated 28 Nov 2023

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
9 Oct 2026, 18:17 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

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