Mazdutide

Mechanism (as reported)

Research described mazdutide as a dual agonist of GLP-1R and GCGR (glucagon-like peptide-1 and glucagon receptors). (PMIDs: 40421736, 37943529, 41407860, 41407859, 38092790, 40479843)

Key findings (each cites a source)

• A systematic review and network meta-analysis of randomized controlled trials reported that mazdutide was among seven GLP-1 receptor agonists/polyagonists included for weight-loss outcomes in obesity or overweight, with primary outcome defined as percentage change in body weight from baseline. (PMIDs: 39305981) [PMID 39305981]
• A phase 3 randomized, double-blind, placebo-controlled trial in Chinese adults with obesity/overweight reported mean percentage body-weight change at week 32 of -10.09% with 4 mg mazdutide and -12.55% with 6 mg mazdutide versus 0.45% with placebo, and reported that the proportion achieving at least 5% weight reduction at week 32 was higher with mazdutide than placebo. (PMIDs: 40421736) [PMID 40421736]
• The same phase 3 obesity/overweight trial reported that at week 48, mean percentage body-weight change was -11.00% (4 mg), -14.01% (6 mg), and 0.30% (placebo). (PMIDs: 40421736) [PMID 40421736]
• In the phase 2 randomized, double-blind, placebo-controlled trial in Chinese adults with type 2 diabetes, the primary outcome was change in HbA1c at week 20, and reported mean HbA1c reductions with mazdutide (range -1.41% to -1.67%) versus placebo (0.03%). (PMIDs: 37943529) [PMID 37943529]
• In the phase 2 trial in Chinese adults with type 2 diabetes, the same report stated that mean percent body-weight change at week 20 was dose dependent and reached up to -7.1% with mazdutide, with dulaglutide and placebo also reported. (PMIDs: 37943529) [PMID 37943529]
• In Chinese adults with type 2 diabetes, a randomized phase 3 trial comparing mazdutide with dulaglutide reported that both mazdutide doses showed non-inferiority and superiority to dulaglutide for mean change in HbA1c from baseline to week 28. (PMIDs: 41407860) [PMID 41407860]
• In that same phase 3 type 2 diabetes trial, significantly greater reductions in body weight were reported with mazdutide than with dulaglutide at week 28. (PMIDs: 41407860) [PMID 41407860]
• In a phase 3 trial in Chinese adults with type 2 diabetes (mazdutide monotherapy vs placebo), the primary endpoint at week 24 was HbA1c, and the report stated that mazdutide significantly reduced HbA1c versus placebo. (PMIDs: 41407859) [PMID 41407859]
• In the same placebo-controlled type 2 diabetes phase 3 trial, weight loss at week 24 was reported in the mazdutide groups versus placebo. (PMIDs: 41407859) [PMID 41407859]
• A phase 2 randomized controlled trial (interim analysis) in Chinese overweight adults or adults with obesity reported mean percentage body-weight changes at week 24 of -6.7% (3 mg), -10.4% (4.5 mg), -11.3% (6 mg) versus 1.0% with placebo, and stated dose-associated differences versus placebo were statistically significant. (PMIDs: 38092790) [PMID 38092790]
• Preclinical research in a male db/db mouse model investigated mazdutide versus dulaglutide using behavioural tests, brain pathology assessments, and multi-omics analysis, reporting improvements in cognitive performance and neurodegenerative markers with mazdutide compared with dulaglutide in that model. (PMIDs: 40479843) [PMID 40479843]
• A systematic review of emerging pharmacotherapies for obesity reported that there were ongoing phase 3 trials on GLP-1/glucagon receptor agonists including mazdutide (and also survodutide) among the included pipeline agents. (PMIDs: 39952695) [PMID 39952695]