Systematic Review on the Effectiveness of Strategies for Increasing Insulin Bioavailability in Oral Route Delivery Systems Based on Manufacturing Techniques and Materials Used

Diabetes is a metabolic disease characterized by hyperglycemia due to impaired insulin secretion, insulin action, or both. All patients with type 1 diabetes and many type 2 diabetes require insulin therapy to achieve reasonable glycemic control. During this time, insulin is given through the subcutaneous injection route because it can be destroyed by gastric acid when given orally. Until now, many studies have developed oral insulin therapy using various delivery system strategies. This systematic literature review aims to answer several questions about the effect of technique and material on increasing oral insulin bioavailability and the best technique and type of material that can produce the best oral insulin bioavailability. We searched for published articles regarding the development of oral route insulin. Bioavailability parameters were assessed based on plasma insulin levels for relative bioavailability values and/or plasma glucose levels for pharmacological bioavailability values. Conclusion: The manufacturing technique in the delivery system affects insulin stability in maintaining its conformation to provide a therapeutic effect. The type of substance affects insulin bioavailability through its properties in paving the way for insulin across various barriers in the digestive tract. To date, the best results in the development of oral insulin have obtained oral insulin bioavailability of 73.10% achieved by mesoporous silica nanoparticles (MSN) delivery system with layer-by-layer technique coated with [poly (methacrylic acid-co-vinyl triethoxylsilane)] (PMV)]. Keywords: bioavailability, diabetes, insulin, nanoparticles, oral delivery system.

Comparative efficacy of oral insulin sensitizers metformin, thiazolidinediones, inositol, and berberine in improving endocrine and metabolic profiles in women with PCOS: a network meta-analysis

Background Multiple oral insulin-sensitizing agents, such as metformin, thiazolidinediones, inositols, and berberine, have been proven safe and efficacious in improving the endocrine, metabolic, and reproductive abnormalities seen in polycystic ovary syndrome (PCOS), providing more options for healthcare providers and patients. These oral insulin sensitizers are more convenient, practical, and economic than agents that need to be injected. A comparison of the clinical effectiveness of the four different classes of oral insulin sensitizers in PCOS has not been explored, leading to clinical uncertainty about the optimal treatment pathway. The present study aims to compare the effects of oral insulin sensitizers on endocrine and metabolic profiles in women with PCOS. Methods We identified randomized controlled trials for PCOS from a variety of databases, published from January 2005 to October 2020. Outcomes included changes in menstrual frequency, improvements in hyperandrogenism and glucolipid metabolism and adverse side effects. A random-effects network meta-analysis was performed. Results Twenty-two trials comprising 1079 patients with PCOS were included in this study. Compared with metformin, treatment with myo-inositol + d-chiro-inositol was associated with a greater improvement in menstrual frequency (odds ratio 14.70 [95% confidence interval (CI) 2.31–93.58]). Myo-inositol + d-chiro-inositol and metformin + thiazolidinediones combination therapies were superior to respective monotherapies in reducing total testosterone levels. Thiazolidinediones, metformin + thiazolidinediones, and myo-inositol + d-chiro-inositol were associated with a lower insulin resistance index (HOMA-IR) compared with that in metformin alone (mean differences: − 0.72 [95% CI (− 1.11)–(− 0.34)] to − 0.89 [95% CI (− 1.460)–(− 0.32)]). Metformin + thiazolidinediones treatment was associated with lower triglyceride levels compared with that in metformin and thiazolidinediones monotherapy, while thiazolidinediones was superior to metformin in increasing high-density lipoprotein cholesterol and decreasing fasting plasma glucose, triglycerides, low-density lipoprotein cholesterol, and gastrointestinal adverse events. Conclusions Ours is the first study to report that for women with PCOS, myo-inositol combined with d-chiro-inositol and metformin combined with thiazolidinediones appear superior to metformin alone in improving insulin resistance and decreasing total testosterone. Myo-inositol combined with d-chiro-inositol is particularly efficacious in menstrual recovery. Thiazolidinediones and metformin combined with thiazolidinediones improve lipid metabolism better than metformin alone. Trial registration PROSPERO CRD42020211524