Oral delivery of insulin for treatment of diabetes: status quo, challenges and opportunities

J Pharm Pharmacol. 2016 Sep;68(9):1093-108. doi: 10.1111/jphp.12607. Epub 2016 Jun 30.


Objectives: Diabetes mellitus is characterised by progressive β-cell destruction and loss of function, or loss of ability of tissues to respond to insulin. Daily subcutaneous insulin injection is standard management for people with diabetes, although patient compliance is hard to achieve due to the inconvenience of injections, so other forms of delivery are being tested, including oral administration. This review summarises the developments in oral insulin administration.

Methods: The PubMed database was consulted to compile this review comparing conventional subcutaneous injection of insulin to the desired oral delivery.

Key findings: Oral administration of insulin has potential benefits in reducing pain and chances of skin infection, improving the portal levels of insulin and avoiding side effects such as hyperinsulinemia, weight gain and hypoglycaemia. Although oral delivery of insulin is an ideal administration route for patients with diabetes, several physiological barriers have to be overcome. An expected low oral bioavailability can be attributed to its high molecular weight, susceptibility to enzymatic proteolysis and low diffusion rate across the mucin barrier.

Conclusions: Strategies for increasing the bioavailability of oral insulin include the use of enzyme inhibitors, absorption enhancers, mucoadhesive polymers and chemical modification for endogenous receptor-mediated absorption. These may help significantly increase patient compliance and disease management.

Keywords: diabetes; formulation; insulin; oral; tablet.

Publication types

  • Review

MeSH terms

  • Administration, Oral
  • Biological Availability
  • Diabetes Mellitus / drug therapy*
  • Drug Delivery Systems*
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / pharmacokinetics
  • Hypoglycemic Agents / therapeutic use
  • Insulin / administration & dosage*
  • Insulin / pharmacokinetics
  • Insulin / therapeutic use


  • Hypoglycemic Agents
  • Insulin