Table 1.

Oral, microneedle, and subcutaneous insulin comparison (Jin et al., 2018; Zhao et al., 2022; Chellathurai et al. 2023).

Parameters	Oral insulin	Microneedle insulin	Injection insulin
Patient acceptability	Convenience and patient compliance	Self-administrable, negligible pain and lesser side-effects	Local injury and pain Hypoglycemic shock Lesser compliance
Pharmacological factors	Mimics pancreatic insulin pathway	The absence of proteolytic enzymes and harsh pH in the skin or mucosal layers meant for INS-MN insertion renders INS safe and effective to be administered	Only 20% reach the target due to the shorter half-life and faster metabolism in the liver and kidney
Pharmacokinetic factors	Low absorption and low bioavailability (1-2%)	Faster onset of action Maximum drug utilization and higher bioavailability	100% bioavailable Repeated multiple dosing required to maintain normoglycemia
Hepatic first-pass effect	Hepatic first-pass effect	Bypasses metabolic pathway	Faster metabolism
Degradation threshold	Easily degraded in the acidic stomach	Could be protected from degradation, by loading as core–shell or coated insulin nanoparticles	Shorter half-lives of insulin require modifications to overcome the same
Pharmaceutical parameter	Need for permeation enhancers Larger dose requirement	Less dose requirement Increased stability of insulin (dry state) Inter- and intra-personal variability makes dose adjustment difficult	Stabilizers and modifiers requirement. Larger doses and repeated administration are necessary