Emerging technologies to achieve oral delivery of GLP-1 and GLP-1 analogs for treatment of type 2 diabetes mellitus (T2DM)

  1. Shengwu Ma1,2*,
  2. Liang We3,
  3. Hongji Yang3,
  4. Shaoping Deng3,
  5. Anthony M. Jevnikar1

Author Affiliations

  • 1Matthew Mailing Centre for Translational Transplantation Studies, Lawson Health Research Institute, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 5A5, CANADA
  • 2Department of Biology, University of Western Ontario, London, Ontario N6A 5B7, CANADA
  • 3Sichuan Provincial Peoples Hospital, Chengdu, Sichuan Province, PR. CHINA

Can J Biotech, Volume 1, Issue 1, Pages 1-10, DOI: 10.24870/cjb.2017-000107

Received: Mar 16, 2017; Revised: Apr 21, 2017; Accepted: Apr 22, 2017

Abstract

Glucagon-like peptide-1 (GLP-1) is a gastrointestinal (GI) peptide hormone that stimulates insulin secretion, gene expression and -cell proliferation, representing a potentially novel and promising therapeutic agent for the treatment of T2DM. DPP-IV-resistant, long-acting GLP-1 analogs have already been approved by FDA as injectable drugs for treating patients with T2DM. Oral delivery of therapeutic peptides and proteins would be preferred owing to advantages of lower cost, ease of administration and greater patient adherence. However, oral delivery of proteins can be affected by rapid enzymatic degradation in the GI tract and poor penetration across the intestinal membrane, which may require amounts that exceed practical consideration. Various production strategies have been explored to overcome challenges associated with the oral delivery of therapeutic peptides and proteins. The goal of this review is to provide an overview of the current state of progress made towards the oral delivery of GLP-1 and its analogs in the treatment of T2DM, with special emphasis on the development of plant and food-grade bacterial delivery systems. Recently, genetically engineered plants and food-grade bacteria have been increasingly explored as novel carrier systems for the oral delivery of peptide and protein drugs. These have a largely unexplored potential to serve both as an expression system and as a delivery vehicle for clinically relevant, cost effective therapeutics. As such, they hold great promise for human biopharmaceuticals and novel therapies against various diseases.

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