Efficacy and safety of oral insulin versus placebo for patients with diabetes mellitus: A systematic review and meta-analysis.

OBJECTIVE: Compliance to insulin injections is poor due to difficulty in subcutaneous administration. Hence, there is a need of an oral formulation of insulin. Oral insulin is currently under investigation. The present analysis aimed to evaluate oral insulin versus placebo for patients with diabetes mellitus (type-1 and type-2). MATERIALS AND METHODS: Results from PUBMED and MEDLINE were searched and compiled from January 1, 2000 to January 9, 2020. Postprandial blood glucose excursions (2PPG), glycated hemoglobin (HbA1c), C-peptide levels, and immune antibody (IAA) levels were compared between the arms. In addition, time to diabetes and safety of oral insulin were discussed. RESULTS: Thirteen out of 1778 trials were included to the analysis. Oral insulin was found to induce significant reduction in mean 2PPG excursion (standardized mean difference [SMD]: -1.94, 95% CI: -3.20 to -0.68, I2 = 91.81, P < 0.005) and mean IAA levels (SMD:-0.49, 95% CI: -0.82 to -0.16, I2 = 27.12, P < 0.005) compared with placebo. Mean C-peptide levels were notably lower in the oral insulin arm. However, the difference was not statistically significant. No significant difference was observed in mean HbA1c levels. The rate of development of type-1 diabetes was not significantly influenced by oral insulin. No deaths or treatment-related serious adverse events were reported. CONCLUSION: Oral insulin provided significant benefits for acute maintenance of diabetes mellitus. It elicited lower immune response and was well tolerated. This new formulation has potential to augment the management of diabetes mellitus. More studies are required to assess its long-term effects.

Microneedles for transdermal drug delivery: a systematic review.

Transdermal route has been explored for various agents due to its advantage of bypassing the first pass effect and sustained release of drug. Due to strong barrier properties of the skin, mainly stratum corneum (SC), the delivery of many therapeutic agents across the skin has become challenging. Few drugs with specific physicochemical properties (molecular weight <500 Da, adequate lipophilicity, and low melting point) can be effectively administered via transdermal route. However, delivery of hydrophilic drugs and macromolecular agents including peptides, DNA and small interfering RNA is challenging. Drug penetration through the SC may involve bypass or reversible disruption of SC layer by various means. Recently, the use of micron-scale needles has been proposed in increasing skin permeability and shown to dramatically increase permeation, especially for macromolecules. Microneedles (MNs) can penetrate through the SC layer of the skin into the viable epidermis, avoiding contact with nerve fibers and blood vessels that reside primarily in the dermal layer. This review summarizes the types of MNs and fabrication techniques of different types of MNs. The safety aspects of the materials used for fabrication have been discussed in detail. Biological applications and relevant phase III clinical trials are also highlighted.