Insulin Therapy: Future Perspectives

Abstract

Background: Insufficient insulin secretion is a core pathogenetic mechanism of diabetes mellitus and therefore, insulin therapy remains the cornerstone of management. Over the past 100 years, much progress has been made in the development of insulin therapy, including elaboration of novel insulin formulations and delivery methods. Areas of Uncertainty: Despite significant advances, there are still many barriers, challenges, and uncertainties involving insulin therapy. With newer pharmacological and technological approaches, there are many potential drawbacks to be addressed, such as immunogenicity, biocompatibility, degradation/clearance of delivery materials, stability, precision of dosing, reproducibility, predictability of performance, and safety over time, etc. In addition, the new formulations/delivery systems should be cost-effective and accessible. Data Sources: A literature search of original and review articles, editorials, and meta-analyses in Medline/PubMed and Google Scholar has been performed. ClinicalTrials.gov website was searched for ongoing relevant clinical trials. Therapeutic Advances: New insulin formulations (ultralong basal and ultrarapid analogues) were designed to obtain a prolonged, flatter profile, with less hypoglycemia and improvement of postprandial glucose control, respectively. The next generation of insulin therapy is probably best represented by the “smart” (glucose-responsive) insulins, which deliver it according to an endogenous glucose-sensing feedback mechanism. Another area of continuous advances includes insulin delivery systems with new jet injectors, smart pens, patch pumps, and other needle-free devices for subcutaneous administrations. Many alternative routes of insulin delivery (pulmonary, nasal, buccal, oral, and transdermal) have also been explored, with some reaching clinical use. The digitalization of diabetes care has made considerable progress in the past several years and will most probably make even more so in the near future. Conclusions: The improved insulin formulations, newer delivery methods/routes, and digital technologies are rapidly becoming effective and have great potential to improve metabolic control as well as other outcomes, including quality of life of persons living with diabetes mellitus.

Immunogenicity of Botulinum Toxin Formulations: Potential Therapeutic Implications

“…Treatment with initial insulin formulations showed both insulin-specific nAbs and antibodies to other drug components [44]. However, replacing impure animal insulins with highly purified porcine insulins and, more recently, recombinant and semisynthetic human insulin preparations has vastly reduced-although not completely eliminated-the occurrence of immunogenicity [44,51,52].…”

Current State and Principles of Basal Insulin Therapy in Type 2 Diabetes

“…Finally, no differences were found in the efficacy or the risk of hypoglycemia when comparing Glar-300 and Deg-200 (Fig. 7) [58,[60][61][62]. On the other hand, studies have shown that, in relation to weight, Det showed less weight gain than NPH and Glar-100.…”

“…On the other hand, studies have shown that, in relation to weight, Det showed less weight gain than NPH and Glar-100. Likewise, a lower weight gain was documented with Glar-300 than Glar-100 (Table 5) [38][39][40][56][57][58][59][60][61][62][63]. Moreover, when evaluating the average doses of BI, it was found that with the use of Deg-100, a lower dose was required (compared to Glar-100), while with Glar-300, a higher average dose was required (compared to Glar-100) [58,59].…”

Nanofiber-based systems intended for diabetes

“…To obviate these restrictions, an immense variety of delivery methods were investigated to control blood glucose levels, including oral, nasal, pulmonary, and transdermal approaches, etc. [7][8][9]. Nevertheless, each of these methods encounters with some limitations including poor permeability across the barriers of body, possible allergic or irritation reactions, difficulty to achieve high plasma drug concentration, and low or variable bioavailability owning to degradation by proteolytic enzymes [10][11][12][13][14][15][16][17].…”