Delving into the Latest Updates on Taspoglutide with Synapse

Overview

Basic Info

Drug Type

Synthetic peptide

Synonyms

Taspoglutide (USAN/INN), BIM 51077, BIM-51077

+ [10]

Target

GLP-1R

Mechanism

GLP-1R agonists(Glucagon-like peptide 1 receptor agonists)

Therapeutic Areas

Cardiovascular DiseasesEndocrinology and Metabolic Disease

Active Indication-

Inactive Indication

Cardiovascular DiseasesDiabetes Mellitus, Noninsulin-Dependent, 2Diabetes Mellitus, Type 2+ [1]

Originator Organization

Ipsen SA

Active Organization-

Inactive Organization

Hoffmann-La Roche, Inc.

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

Structure

Molecular FormulaC152H232N40O45

InChIKeyWRGVLTAWMNZWGT-VQSPYGJZSA-N

CAS Registry275371-94-3

Gene Sequence

Sequence Code 108690

Source: *****

A multi-center, single-dose, open-label, randomized, parallel group study to investigate the reduction of initial taspoglutide Cmax after administration of 20 mg taspoglutide 10% Sustained Release Formulation (SRF) using three modified formulations as compared to the current Phase 3 formulation in healthy volunteers. - Taspoglutide BE study in healthy volunteers

Start Date26 Oct 2010

Sponsor / Collaborator

Hoffmann-La Roche Ltd.

100 Clinical Results associated with Taspoglutide

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100 Translational Medicine associated with Taspoglutide

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100 Patents (Medical) associated with Taspoglutide

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55

Literatures (Medical) associated with Taspoglutide

01 Dec 2021·EClinicalMedicine

Association of glucagon-like peptide 1 analogs and agonists administered for obesity with weight loss and adverse events: a systematic review and network meta-analysis

Article

Author: Murad, M Hassan ; Khoshbin, Katayoun ; Khanna, Lehar ; Davitkov, Perica ; Camilleri, Michael ; Vosoughi, Kia ; Atieh, Jessica ; Prokop, Larry J

BACKGROUND:

Comparative effectiveness of 7 glucagon-like peptide 1 (GLP-1) agents on weight loss (WL) in obesity remains unknown.

METHODS:

We performed a systematic review, network meta-analysis (NMA) utilizing the following data sources: MEDLINE, EMBASE, Scopus, Cochrane Central and clinical trial registries, from inception to March 2, 2021. The prespecified criteria for study inclusion were randomized clinical trials (RCTs) of ≥12 weeks' duration. The data appraisal and extraction were performed by two investigators independently, using the published reports. The main outcomes and statistical methods were weight loss over placebo (WLOP) and adverse events (AEs) among GLP-1 agents using random-effects NMA (frequentist approach); relative ranking using surface under the cumulative ranking (SUCRA) method and certainty of evidence using grading of recommendations, assessment, development and evaluations (GRADE).

FINDINGS:

64 RCTs (from 2004 to 2021) included 27018 patients (median of age, 55.1 years old; 57.4% women; baseline weight 94.8kg and BMI 33.0kg/m²; trial duration 26 weeks). Direct meta-analysis showed significant WLOP with: -1.44kg (95% CI, -2.14 to -0.74) with dulaglutide ≥1.5 mg; -1.82kg (-2.42 to -1.23) with exenatide immediate release (IR); -2.20kg (-4.31 to -0.08) with exenatide extended release (ER); -3.20kg (-6.53 to 0.15) with efpeglenatide; -2.72kg (-3.35 to -2.09) with liraglutide ≤1.8mg; -4.49kg (-5.26 to -3.72) with liraglutide >1.8mg; -0.62kg (-1.22 to -0.02) with lixisenatide; -4.33kg (-5.71 to -3.00) with semaglutide SQ <2.4mg; -9.88kg (-13.17 to -6.59) with semaglutide SQ 2.4mg; -2.73kg (-4.81 to -0.65) with semaglutide oral; and -1.71kg (-2.64 to -0.78) with taspoglutide. Highest WLOP were with semaglutide SQ 2.4mg and <2.4mg, and liraglutide >1.8mg (SUCRAs 100, 86.1, 82.8 respectively). Highest SUCRAs for discontinuation due to AEs were with taspoglutide and liraglutide >1.8mg. Risk of bias was high or unclear for random sequence generation (29.7%), allocation concealment (26.6%), and incomplete outcome data (26.6%). Heterogeneity (I² >50%) in WL and AEs reflected magnitude, not direction of effect.

01 Jul 2021·Cell reportsQ1 · BIOLOGY

Structure and dynamics of semaglutide- and taspoglutide-bound GLP-1R-Gs complexes

Q1 · BIOLOGY

ArticleOA

Author: Sexton, Patrick M ; Wootten, Denise ; Liang, Yi-Lynn ; Belousoff, Matthew J ; Zhang, Xin ; Danev, Radostin

The glucagon-like peptide-1 receptor (GLP-1R) regulates insulin secretion, carbohydrate metabolism, and appetite and is an important target for treatment of type 2 diabetes and obesity. Multiple GLP-1R agonists have entered into clinical trials, with some, such as semaglutide, progressing to approval. Others, including taspoglutide, failed due to the high incidence of side effects or insufficient efficacy. GLP-1R agonists have a broad spectrum of signaling profiles, but molecular understanding is limited by a lack of structural information on how different agonists engage with the GLP-1R. Here, we report cryoelectron microscopy (cryo-EM) structures and cryo-EM 3D variability analysis of semaglutide- and taspoglutide-bound GLP-1R-Gs protein complexes. These reveal similar peptide interactions to GLP-1 but different motions within the receptor and bound peptides, providing insights into the molecular determinants of GLP-1R peptide engagement.

01 Sep 2019·Clinical pharmacokineticsQ2 · MEDICINE

Assessment of Drug–Drug Interactions between Taspoglutide, a Glucagon-Like Peptide-1 Agonist, and Drugs Commonly Used in Type 2 Diabetes Mellitus: Results of Five Phase I Trials

Q2 · MEDICINE

Article

Author: Mangold, Bernhard ; Sturm, Stefan ; Brumm, Jochen ; Hofmann, Carsten ; Bogman, Katrijn ; Sturm-Pellanda, Carolina ; Niggli, Markus ; Schmitt, Christophe ; Sauter, Annette ; Giraudon, Mylène

BACKGROUND AND OBJECTIVE:

Taspoglutide, a glucagon-like peptide-1 agonist, like native glucagon-like peptide-1, delays gastric emptying time and prolongs intestinal transit time, which may alter the pharmacokinetics of concomitantly administered oral drugs. The effect of taspoglutide on the pharmacokinetics of five oral drugs commonly used in patients with type 2 diabetes mellitus was assessed in healthy subjects.

METHODS:

Five clinical pharmacology studies evaluated the potential drug-drug interaction between multiple subcutaneous taspoglutide doses and a single dose of lisinopril, warfarin, and simvastatin and multiple doses of digoxin and an oral contraceptive containing ethinylestradiol and levonorgestrel. The extent of interaction was quantified using geometric mean ratios and 90% confidence intervals for the maximum plasma concentration and area under the plasma concentration-time curve. In addition to pharmacokinetics, pharmacodynamic effects were assessed for warfarin and the oral contraceptive.

RESULTS:

Among the tested drugs, the effect of taspoglutide on the pharmacokinetics of simvastatin was most pronounced, on the day of taspoglutide administration, the average exposure to simvastatin was decreased by - 26% and - 58% for the area under the plasma concentration-time curve and maximum plasma concentration, respectively, accompanied by an increase in average exposure to its active metabolite, simvastatin β-hydroxy acid (+ 74% and + 23% for area under the plasma concentration-time curve and maximum plasma concentration, respectively). Although statistically significant changes in exposure were observed for other test drugs, the 90% confidence intervals for the geometric mean ratio for maximum plasma concentration and area under the plasma concentration-time curve were within the 0.7-1.3 interval. No clinically relevant changes on coagulation (for warfarin) and ovulation-suppressing activity (for the oral contraceptive) were apparent.

CONCLUSION:

Overall, multiple doses of taspoglutide did not result in changes in the pharmacokinetics of digoxin, an oral contraceptive containing ethinylestradiol and levonorgestrel, lisinopril, warfarin, and simvastatin that would be considered of clinical relevance. Therefore, no dose adjustments are warranted upon co-administration.

100 Deals associated with Taspoglutide

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External Link

KEGG	Wiki	ATC	Drug Bank
D09723	Taspoglutide	-	DB14027

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Cardiovascular Diseases	Phase 3	US	Hoffmann-La Roche, Inc.	01 Jan 2010
Cardiovascular Diseases	Phase 3	AU	Hoffmann-La Roche, Inc.	01 Jan 2010
Cardiovascular Diseases	Phase 3	BR	Hoffmann-La Roche, Inc.	01 Jan 2010
Cardiovascular Diseases	Phase 3	BG	Hoffmann-La Roche, Inc.	01 Jan 2010
Cardiovascular Diseases	Phase 3	CA	Hoffmann-La Roche, Inc.	01 Jan 2010
Cardiovascular Diseases	Phase 3	CZ	Hoffmann-La Roche, Inc.	01 Jan 2010
Cardiovascular Diseases	Phase 3	DK	Hoffmann-La Roche, Inc.	01 Jan 2010
Cardiovascular Diseases	Phase 3	EE	Hoffmann-La Roche, Inc.	01 Jan 2010
Cardiovascular Diseases	Phase 3	DE	Hoffmann-La Roche, Inc.	01 Jan 2010
Cardiovascular Diseases	Phase 3	HU	Hoffmann-La Roche, Inc.	01 Jan 2010

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00717457 (T-emerge 2, Pubmed \| Diabetes Care)	Phase 3	Diabetes Mellitus, Type 2	1,189	Taspoglutide 10 mg	refxtksiwz(yujdxrdrbc) = utcaaghzve cqdrlchjio (rjjvznzbqv ) View more	-	01 Mar 2013
				Taspoglutide 20 mg	refxtksiwz(yujdxrdrbc) = zmysnrmmvj cqdrlchjio (rjjvznzbqv ) View more
NCT00423501 (Pubmed \| Diabetes Care)	Phase 2	Diabetes Mellitus, Type 2	306	Taspoglutide 5 mg once weekly	ftlkhuyqag(qayuwezjki) = tjzovshzmx qzkjajhslo (eoefgjigmq ) View more	Positive	01 Jul 2009
				Taspoglutide 10 mg once weekly	ftlkhuyqag(qayuwezjki) = alfjoetiks qzkjajhslo (eoefgjigmq ) View more