- |||||||||| maridebart cafraglutide (AMG 133) / Amgen, Mounjaro (tirzepatide) / Eli Lilly
Preclinical, Journal: Glucose-dependent insulinotropic polypeptide receptor signaling alleviates gut inflammation in mice. (Pubmed Central) - Dec 26, 2024
The clinical development of GIP receptor (GIPR)-GLP-1 receptor (GLP-1R) multi-agonists exemplified by tirzepatide and emerging GIPR antagonist-GLP-1R agonist therapeutics such as maritide is increasing interest in the extra-pancreatic actions of incretin therapies...Here, using gain and loss of function studies, we show that GIP alleviates 5-fluorouracil (5FU)-induced gut inflammation, whereas genetic deletion of Gipr exacerbates the proinflammatory response to 5FU in the murine small bowel (SB)...Within the gut, Gipr was localized to non-immune cells, specifically stromal CD146+ cells. Hence, the extra-pancreatic actions of GIPR signaling extend to the attenuation of gut inflammation, findings with potential translational relevance for clinical strategies modulating GIPR action in people with type 2 diabetes or obesity.
- |||||||||| maridebart cafraglutide (AMG 133) / Amgen
Enrollment open: A Study of Maridebart Cafraglutide in Adult Participants With Type 2 Diabetes Mellitus (T2DM) (clinicaltrials.gov) - Dec 1, 2024
P2, N=350, Recruiting,
Hence, the extra-pancreatic actions of GIPR signaling extend to the attenuation of gut inflammation, findings with potential translational relevance for clinical strategies modulating GIPR action in people with type 2 diabetes or obesity. Not yet recruiting --> Recruiting
- |||||||||| Review, Journal: Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity. (Pubmed Central) - Oct 21, 2024
Here I highlight evidence establishing the efficacy of GLP-1-based medicines, while discussing data that inform safety, focusing on muscle strength, bone density and fractures, exercise capacity, gastrointestinal motility, retained gastric contents and anesthesia, pancreatic and biliary tract disorders, and the risk of cancer. Rapid progress in development of highly efficacious GLP-1 medicines, and anticipated differentiation of newer agents in subsets of metabolic disorders, will provide greater opportunities for use of personalized medicine approaches to improve the health of people living with cardiometabolic disorders.
- |||||||||| maridebart cafraglutide (AMG 133) / Amgen
Trial completion: A Study to Evaluate AMG 133 in Chinese Participants With Obesity or Overweight (clinicaltrials.gov) - Sep 20, 2024
P1, N=20, Completed,
Rapid progress in development of highly efficacious GLP-1 medicines, and anticipated differentiation of newer agents in subsets of metabolic disorders, will provide greater opportunities for use of personalized medicine approaches to improve the health of people living with cardiometabolic disorders. Active, not recruiting --> Completed
- |||||||||| maridebart cafraglutide (AMG 133) / Amgen, Mounjaro (tirzepatide) / Eli Lilly
Journal: Characterization of genetic variants of GIPR reveals a contribution of ?-arrestin to metabolic phenotypes. (Pubmed Central) - Jul 26, 2024
Endosomal Gs-mediated signalling of the variants shows a ?-arrestin dependency and genetic ablation of ?-arrestin 2 impairs cyclic adenosine monophosphate production and decreases GIP efficacy on glucose control in male mice. This study highlights a crucial impact of ?-arrestins in regulating GIPR signalling and overall preservation of biological activity that may facilitate new developments in therapeutic targeting of the GIPR system.
- |||||||||| maridebart cafraglutide (AMG 133) / Amgen
Journal: Antagonizing GIPR adds fire to the GLP-1R flame. (Pubmed Central) - Jul 9, 2024
This study highlights a crucial impact of ?-arrestins in regulating GIPR signalling and overall preservation of biological activity that may facilitate new developments in therapeutic targeting of the GIPR system. Unimolecular co-agonists at the GLP-1/GIP receptors have recently achieved remarkable anti-obesogenic feats; yet, in a recent Phase 1 clinical trial, V
- |||||||||| maridebart cafraglutide (AMG 133) / Amgen
Enrollment closed: A Study to Evaluate AMG 133 in Chinese Participants With Obesity or Overweight (clinicaltrials.gov) - May 28, 2024
P1, N=20, Active, not recruiting,
Unimolecular co-agonists at the GLP-1/GIP receptors have recently achieved remarkable anti-obesogenic feats; yet, in a recent Phase 1 clinical trial, V Recruiting --> Active, not recruiting
- |||||||||| maridebart cafraglutide (AMG 133) / Amgen
P1 data, Journal: Phase I results for AMG 133. (Pubmed Central) - Mar 18, 2024
Not yet recruiting --> Recruiting No abstract available
- |||||||||| Discovery of AMG 133, a Novel GIPR Antagonist Antibody & GLP-1 Peptide Conjugate for the Treatment of Obesity () - Aug 9, 2023 - Abstract #ADCUSA2023ADC_USA_6;
Trial completion date: Dec 2024 --> Dec 2025 Discuss the design of GIPR antibody and GLP-1 peptide bispecific conjugates and site-specific conjugation process to attach GLP-1 analogues to GIPR antibody; View the preclinical data of AMG 133 that demonstrated robust body weight reduction and significantly improved metabolic parameters; Describe AMG 133 Phase I clinical results that showed efficacy and tolerability with desired pharmacokinetic profiles
- |||||||||| AMG 133 / Amgen, Mounjaro (tirzepatide) / Eli Lilly
Review, Journal: Beyond the pancreas: contrasting cardiometabolic actions of GIP and GLP1. (Pubmed Central) - Mar 20, 2023
Discuss the design of GIPR antibody and GLP-1 peptide bispecific conjugates and site-specific conjugation process to attach GLP-1 analogues to GIPR antibody; View the preclinical data of AMG 133 that demonstrated robust body weight reduction and significantly improved metabolic parameters; Describe AMG 133 Phase I clinical results that showed efficacy and tolerability with desired pharmacokinetic profiles We interpret the clinical and mechanistic data obtained for different agents that enable weight loss and glucose control for the treatment of obesity and type 2 diabetes mellitus, respectively, by activating or blocking GIPR signalling, including the GIPR-GLP1R co-agonist tirzepatide, as well as the GIPR antagonist-GLP1R
- |||||||||| maridebart cafraglutide (AMG 133) / Amgen
Enrollment open: Dose-ranging Study to Evaluate the Efficacy, Safety, and Tolerability of AMG 133 in Adult Subjects With Overweight or Obesity, With or Without Type 2 Diabetes Mellitus (clinicaltrials.gov) - Jan 30, 2023
P2, N=570, Recruiting,
We interpret the clinical and mechanistic data obtained for different agents that enable weight loss and glucose control for the treatment of obesity and type 2 diabetes mellitus, respectively, by activating or blocking GIPR signalling, including the GIPR-GLP1R co-agonist tirzepatide, as well as the GIPR antagonist-GLP1R Not yet recruiting --> Recruiting
- |||||||||| Review, Journal: An update on peptide-based therapies for type 2 diabetes and obesity. (Pubmed Central) - Jan 8, 2023
Particularly high efficacy in both glucose- and weight lowering capacities has also been observed with the GLP-1R/GIP-R unimolecular dual agonist, tirzepatide...Other pharmacological approaches to chronic weight management include the human monoclonal antibody, bimagrumab which blocks activin type II receptors and is associated with growth of skeletal muscle, an antibody blocking activation of GIPR to which are conjugated GLP-1R peptide agonists (AMG-133), and the melanocortin-4 receptor agonist, setmelanotide for use in certain inherited obesity conditions. The high global demand for the GLP-1R agonists liraglutide and semaglutide as anti-obesity agents has led to shortage so that their use in T2D therapy is currently being prioritized.
- |||||||||| maridebart cafraglutide (AMG 133) / Amgen
Trial completion: Single and Multiple Ascending Dose Study of AMG 133 in Participants With Obesity (clinicaltrials.gov) - Dec 6, 2022
P1, N=110, Completed,
The high global demand for the GLP-1R agonists liraglutide and semaglutide as anti-obesity agents has led to shortage so that their use in T2D therapy is currently being prioritized. Active, not recruiting --> Completed
- |||||||||| maridebart cafraglutide (AMG 133) / Amgen
Enrollment open, Trial completion date, Trial primary completion date: Single and Multiple Ascending Dose Study of AMG 133 in Participants With Obesity (clinicaltrials.gov) - Apr 11, 2022
P1, N=112, Recruiting,
Recruiting --> Active, not recruiting Active, not recruiting --> Recruiting | Trial completion date: May 2022 --> Nov 2022 | Trial primary completion date: May 2022 --> Nov 2022
- |||||||||| Journal: Emerging glucagon-like peptide 1 receptor agonists for the treatment of obesity. (Pubmed Central) - Jan 27, 2022
There is a strong interest in developing obesity treatments based on glucagon-like peptide-1 (GLP-1) agonism, which have proved to limit morbidity and mortality in type 2 diabetes.Areas covered: This review provides an overview of current compounds containing GLP-1 receptor agonism in clinical development for obesity, with mono-activity at the GLP-1 receptor (PF-0688296, glutazumab, semaglutide) or engaging one or more other endogenous hormonal systems involved in energy balance and metabolism, including glucagon, oxyntomodulin, glucose-dependent inhibitory peptide and amylin (CT-868, CT-388, AMG 133, tirzepatide, NNC9204-1177, JNJ-54728518, SAR425899, pegapamodutide, MK8521, cotadutide, efinopegdutide, BI-456906, cagrilintide + semaglutide 2,4 mg, HM15211, NNC9204-1706).Expert opinion: Many novel compounds employing GLP-1 receptor agonism are in clinical development. Semaglutide is farthest in clinical development and will presumably become a benchmark for this class of novel anti-obesity compounds.
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