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, Linong; Gao, Leili; Jiang, Hongwei; Yang, Jing; Lei, Yu; Wen, Jinyu; Cai, Chenghang; Deng, Huan; Feng, Liqi; Song, Baili; Ma, Qingyang; Qian, Lei

doi:10.1016/j.eclinm.2022.101691

Cited by 40 publications

(37 citation statements)

References 15 publications

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“…47,48 Indeed, nausea, among other GI disorders, is also reported with dual GIP/GLP-1RAs and other GCGR/GLP-1RAs in people with overweight/obesity. 39,40,42 Importantly, in our studies, BI 456906 showed clinically significant and meaningful body weight loss (>5% 49 ) at 6 weeks' treatment and, at 16 weeks' treatment, placebo-corrected body weight loss of 13.8% was reported (DS7). In both studies, BI 456906 exposure (C max and AUC 0-168 values) increased in a dose-proportional manner.…”

Section: Discussionmentioning

confidence: 41%

“…on the area postrema and nucleus of the solitary tract) that may contribute to feelings of nausea 47,48 . Indeed, nausea, among other GI disorders, is also reported with dual GIP/GLP‐1RAs and other GCGR/GLP‐1RAs in people with overweight/obesity 39,40,42 …”

Section: Discussionmentioning

confidence: 99%

“…35 However, oxyntomodulin has weak potency and a very short half-life. 5,30,36 Thus, research into longer-acting GCGR/ GLP-1R dual agonists that reduce energy intake and increase energy expenditure, such as cotadutide, 37 DualAG 38 and mazdutide (IBI362), 39,40 is of interest for the treatment of people with overweight/obesity. For example, in two phase Ib trials of mazdutide, placebo-corrected body weight loss of 4.2%-9.9% over 12 weeks was observed in Chinese adults with overweight/obesity.…”

Section: Introductionmentioning

confidence: 99%

“…For example, in two phase Ib trials of mazdutide, placebo-corrected body weight loss of 4.2%-9.9% over 12 weeks was observed in Chinese adults with overweight/obesity. 39,40 Research into glucose-dependent insulinotropic polypeptide (GIP)/GLP-1R dual agonists, such as tirzepatide, 41 is also garnering attention. Indeed, in the phase III SURMOUNT-1 study, tirzepatide produced a placebo-corrected body weight loss of 11.9%-17.8% over 72 weeks in people living with overweight/obesity.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, research into longer‐acting GCGR/GLP‐1R dual agonists that reduce energy intake and increase energy expenditure, such as cotadutide, 37 DualAG 38 and mazdutide (IBI362), 39,40 is of interest for the treatment of people with overweight/obesity. For example, in two phase Ib trials of mazdutide, placebo‐corrected body weight loss of 4.2%–9.9% over 12 weeks was observed in Chinese adults with overweight/obesity 39,40 . Research into glucose‐dependent insulinotropic polypeptide (GIP)/GLP‐1R dual agonists, such as tirzepatide, 41 is also garnering attention.…”

Section: Introductionmentioning

confidence: 99%

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Phase I studies of the safety, tolerability, pharmacokinetics and pharmacodynamics of the dual glucagon receptor/glucagon‐like peptide‐1 receptor agonistBI456906

Jungnik

Plum‐Mörschel²,

Kapitza

et al. 2023

Diabetes Obesity Metabolism

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Aim To report two phase I studies of the novel subcutaneous glucagon‐like peptide‐1 receptor/glucagon receptor (GLP‐1R/GCGR) dual agonist BI 456906 versus placebo in healthy volunteers and people with overweight/obesity. Materials and Methods A phase Ia study (NCT03175211) investigated single rising doses (SRDs) of BI 456906 in 24 males with a body mass index (BMI) of 20–<30 kg/m2. A phase Ib study (NCT03591718) investigated multiple rising doses (MRDs) of BI 456906 (escalated over 6 [Part A] or 16 [Part B] weeks) in 125 adults with a BMI of 27–40 kg/m2. Results In the SRD study (N = 24), mean body weight decreased with increasing BI 456906 dose. In the MRD study, the maximum decreases in placebo‐corrected mean body weight were at week 6 (–5.79%, dosage schedule [DS] 1; Part A) and week 16 (–13.8%, DS7; Part B). BI 456906 reduced plasma amino acids and glucagon, indicating target engagement at GCGRs and GLP‐1Rs. Drug‐related adverse events (AEs) increased with BI 456906 dose. The most frequent drug‐related AE with SRDs was decreased appetite (n = 9, 50.0%), and two subjects (8.3%) did not complete the trial because of AEs (nausea and vomiting). During MRD Part A (N = 80), 10 subjects (12.5%) discontinued BI 456906, most commonly because of a cardiac or vascular AE (n = 6, 7.5%); during Part B (N = 45), eight subjects (17.8%) discontinued BI 456906, mainly because of AEs (n = 6, 13.3%), most commonly gastrointestinal disorders. Conclusions BI 456906 produced a placebo‐corrected body weight loss of 13.8% (week 16), highlighting its potential to promote clinically meaningful body weight loss in people with overweight/obesity.

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