Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2022 Jul-Aug;54(4):244-252.
doi: 10.4103/ijp.ijp_1135_20.

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

Saili Dharadhar  1 , Amit Sharma  1 , Debasis Dey  2
Affiliations
Meta-Analysis

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

Saili Dharadhar et al. Indian J Pharmacol. 2022 Jul-Aug.

Abstract

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.

Keywords: Clinical trials; diabetes mellitus; meta-analysis; oral insulin.

PubMed Disclaimer

Conflict of interest statement

None

Figures

Figure 1
Figure 1
Study selection flowchart
Figure 2
Figure 2
Forest plot: Mean PPG excursion at 2-h. *Pooled data from all doses. PPG = Postprandial plasma glucose
Figure 3
Figure 3
Forest plot: Mean HbA1c at 12 months. HbA1c = Glycated hemoglobin
Figure 4
Figure 4
Forest plot: Mean C-peptide
Figure 5
Figure 5
Forest plot: Mean auto antibody levels to insulin
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2013;36(1):S67–74. - PMC - PubMed
    1. Abbatecola AM, Rizzo MR, Barbieri M, Grella R, Arciello A, Laieta MT, et al. Postprandial plasma glucose excursions and cognitive functioning in aged type 2 diabetics. Neurology. 2006;67:235–40. - PubMed
    1. Pundir CS, Chawla S. Determination of glycated hemoglobin with special emphasis on biosensing methods. Anal Biochem. 2014;444:47–56. - PubMed
    1. Jones AG, Hattersley AT. The clinical utility of C-peptide measurement in the care of patients with diabetes. Diabet Med. 2013;30:803–17. - PMC - PubMed
    1. He L, Sabet A, Djedjos S, Miller R, Sun X, Hussain MA, et al. Metformin and insulin suppress hepatic gluconeogenesis through phosphorylation of CREB binding protein. Cell. 2009;137:635–46. - PMC - PubMed

MeSH terms