Use of a biomimetic hydrogel depot technology for sustained delivery of GLP-1 receptor agonists reduces burden of diabetes management

Andrea I d'Aquino; Caitlin L Maikawa; Leslee T Nguyen; Katie Lu; Ian A Hall; Carolyn K Jons; Catherine M Kasse; Jerry Yan; Alexander N Prossnitz; Enmian Chang; Sam W Baker; Lars Hovgaard; Dorte B Steensgaard; Hanne B Andersen; Lotte Simonsen; Eric A Appel

doi:10.1016/j.xcrm.2023.101292

Use of a biomimetic hydrogel depot technology for sustained delivery of GLP-1 receptor agonists reduces burden of diabetes management

Cell Rep Med. 2023 Nov 21;4(11):101292. doi: 10.1016/j.xcrm.2023.101292.

Authors

Affiliations

¹ Department of Materials Science & Engineering, Stanford University, Stanford, CA 94025, USA.
² Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
³ Department of Biochemistry, Stanford University, Palo Alto, CA 94305, USA.
⁴ Department of Biology, Stanford University, Stanford, CA 94305, USA.
⁵ Department of Comparative Medicine, Stanford University, Palo Alto, CA 94305, USA.
⁶ Department of Biophysics and Formulations, Global Research Technologies, Novo Nordisk Park, 2760 Maaloev, Denmark.
⁷ Department of Obesity Research, Global Drug Discovery, Novo Nordisk Park, 2760 Maaloev, Denmark.
⁸ Department of Materials Science & Engineering, Stanford University, Stanford, CA 94025, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; ChEM-H Institute, Stanford University, Stanford, CA 94305, USA; Department of Pediatrics (Endocrinology), Stanford University, Stanford, CA 94305, USA; Woods Institute for the Environment, Stanford University, Stanford, CA 94305, USA. Electronic address: eappel@stanford.edu.

Abstract

Glucagon-like peptide-1 (GLP-1) is an incretin hormone and neurotransmitter secreted from intestinal L cells in response to nutrients to stimulate insulin and block glucagon secretion in a glucose-dependent manner. Long-acting GLP-1 receptor agonists (GLP-1 RAs) have become central to treating type 2 diabetes (T2D); however, these therapies are burdensome, as they must be taken daily or weekly. Technological innovations that enable less frequent administrations would reduce patient burden and increase patient compliance. Herein, we leverage an injectable hydrogel depot technology to develop a GLP-1 RA drug product capable of months-long GLP-1 RA delivery. Using a rat model of T2D, we confirm that one injection of hydrogel-based therapy sustains exposure of GLP-1 RA over 42 days, corresponding to a once-every-4-months therapy in humans. Hydrogel therapy maintains management of blood glucose and weight comparable to daily injections of a leading GLP-1 RA drug. This long-acting GLP-1 RA treatment is a promising therapy for more effective T2D management.

Keywords: GLP-1 RA; diabetes; drug delivery; supramolecular hydrogel.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Animals
Biomimetics
Diabetes Mellitus, Type 2* / drug therapy
Glucagon-Like Peptide 1
Glucagon-Like Peptide-1 Receptor / agonists
Humans
Hydrogels / therapeutic use
Hypoglycemic Agents / pharmacology
Hypoglycemic Agents / therapeutic use
Rats

Substances

Hypoglycemic Agents
Glucagon-Like Peptide-1 Receptor
Hydrogels
Glucagon-Like Peptide 1

Abstract

Publication types

MeSH terms

Substances

Grants and funding