Effects on weight loss and glycemic control with SAR441255, a potent unimolecular peptide GLP-1/GIP/GCG receptor triagonist

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Effects on weight loss and glycemic control with SAR441255, a potent unimolecular peptide GLP-1/GIP/GCG receptor triagonist

Bossart, Martin (author): Sanofi, Integrated Drug Discovery Germany, Synthet Med Modal, Frankfurt, Germany.

Wagner, Michael (author): Sanofi, Integrated Drug Discovery Germany, Synthet Med Modal, Frankfurt, Germany.;Dewpoint Therapeut, Frankfurt, Germany.

Elvert, Ralf (author): Sanofi, TA Diabet, Frankfurt, Germany.;Evotec Int GmbH, Gottingen, Germany.

Evers, Andreas (author): Sanofi, Integrated Drug Discovery Germany, Synthet Med Modal, Frankfurt, Germany.;Merck Healthcare KGaA, Discovery Technol, Global Res & Dev, Darmstadt, Germany.

Hubschle, Thomas (author): Sanofi, TA Diabet, Frankfurt, Germany.

Kloeckener, Tim (author): Sanofi, TA Diabet, Frankfurt, Germany.;Boehringer Ingelheim Pharma GmbH & Co KG, Cardiometab Dis Res, Biberach, Germany.

Lorenz, Katrin (author): Sanofi, Integrated Drug Discovery Germany, Synthet Med Modal, Frankfurt, Germany.

Moessinger, Christine (author): Sanofi, TA Diabet, Frankfurt, Germany.

Eriksson, Olof (author): Uppsala universitet,Science for Life Laboratory, SciLifeLab,Translationell avbildning med PET,Antaros Med AB, Mölndal, Sweden

Velikyan, Irina, 1966- (author): Uppsala universitet,Science for Life Laboratory, SciLifeLab,Translationell avbildning med PET,Uppsala Univ Hosp, PET Ctr, Ctr Med Imaging, Uppsala, Sweden

Pierrou, Stefan (author): Antaros Med AB, Mölndal, Sweden.

Johansson, Lars (author): Antaros Med AB, Mölndal, Sweden.

Dietert, Gabriele (author): Sanofi, Preclin Safety, Frankfurt, Germany.

Dietz-Baum, Yasmin (author): Sanofi, Preclin Safety, Frankfurt, Germany.

Kissner, Thomas (author): Sanofi, Preclin Safety, Frankfurt, Germany.

Nowotny, Irene (author): Sanofi, Translat Med & Early Dev, Frankfurt, Germany.

Einig, Christine (author): Sanofi, Clin Sci & Operat, Frankfurt, Germany.

Jan, Christelle (author): Sanofi, Clin Sci & Operat, Chilly Mazarin, France.

Rharbaoui, Faiza (author): Sanofi, Translat Med & Early Dev, Frankfurt, Germany.

Gassenhuber, Johann (author): Sanofi, Translat Med & Early Dev, Frankfurt, Germany.

Prochnow, Hans-Peter (author): Sanofi, Translat Med & Early Dev, Frankfurt, Germany.

Agueusop, Inoncent (author): Sanofi, Clin Sci & Operat, Frankfurt, Germany.

Porksen, Niels (author): Sanofi, Diabet Dev, Frankfurt, Germany.

Smith, William B. (author): NOCCR Alliance Multispecialty Res AMR, Knoxville, TN USA.

Nitsche, Almut (author): Sanofi, Diabet Dev, Frankfurt, Germany.

Konkar, Anish (author): Sanofi, TA Diabet, Frankfurt, Germany.;Eli Lilly & Co, Diabet & Complicat Therapeut Area, Lilly Res Labs, Indianapolis, IN 46285 USA.

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Sanofi, Integrated Drug Discovery Germany, Synthet Med Modal, Frankfurt, Germany Sanofi, Integrated Drug Discovery Germany, Synthet Med Modal, Frankfurt, Germany.;Dewpoint Therapeut, Frankfurt, Germany. (creator_code:org_t)

CELL PRESS, 2022
2022
English.
In: Cell Metabolism. - : CELL PRESS. - 1550-4131 .- 1932-7420. ; 34:1, s. 59-

Related links:: http://www.cell.com/...; show more...; https://urn.kb.se/re...; https://doi.org/10.1...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

Unimolecular triple incretins, combining the activity of glucagon-like peptide-1 (GLP-1), glucose -dependent insulinotropic polypeptide (GIP), and glucagon (GCG), have demonstrated reduction in body weight and improved glucose control in rodent models. We developed SAR441255, a synthetic peptide agonist of the GLP-1, GCG, and GIP receptors, structurally based on the exendin-4 sequence. SAR441255 displays high potency with balanced activation of all three target receptors. In animal models, metabolic outcomes were superior to results with a dual GLP-1/GCG receptor agonist. Preclinical in vivo positron emission tomography imaging demonstrated SAR441255 binding to GLP-1 and GCG receptors. In healthy subjects, SAR441255 improved glycemic control during a mixed-meal tolerance test and impacted biomarkers for GCG and GIP receptor activation. Single doses of SAR441255 were well tolerated. The results demonstrate that integrating GIP activity into dual GLP-1 and GCG receptor agonism provides improved effects on weight loss and glycemic control while buffering the diabetogenic risk of chronic GCG receptor agonism.

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Endocrinology an ...

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Effects on weight loss and glycemic control with SAR441255, a potent unimolecular peptide GLP-1/GIP/GCG receptor triagonist

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