International Journal of Molecular Medical Science, 2024, Vol.14, No.2, 144-152 http://medscipublisher.com/index.php/ijmms 145 2 Types of Insulin and Modes of Delivery 2.1 Rapid-acting insulin analogs Rapid-acting insulin analogs have been developed to closely mimic the body's natural insulin response to meals. These analogs, such as insulin lispro, are designed to be absorbed quickly, allowing for administration at mealtime and reducing the risk of postprandial hyperglycemia. Their rapid onset and shorter duration of action compared to regular human insulin help minimize the risk of hypoglycemia (Nally et al., 2019). Recent innovations include the development of ultrafast-acting insulin analogs, which further enhance postprandial glucose control (Nally et al., 2019). 2.2 Long-acting insulin analogs Long-acting insulin analogs provide a steady, basal level of insulin, which is crucial for maintaining glucose homeostasis throughout the day and night. These analogs, such as insulin glargine and insulin detemir, have been engineered to have a prolonged duration of action and a peakless profile, reducing the risk of nocturnal hypoglycemia and providing more predictable insulin delivery (Cahn et al., 2017). Innovations in this area include the development of even longer-acting insulins, which aim to further reduce the frequency of injections and improve patient compliance (Nally et al., 2019). 2.3 Innovations in insulin formulations The quest for improved insulin formulations has led to significant advancements. Innovations include the development of hepatoselective insulins, which target the liver more effectively, and glucose-responsive insulins, which adjust their activity based on blood glucose levels (Perkins et al., 2021). Additionally, the use of nanoparticles and other novel delivery systems has shown promise in enhancing the stability and bioavailability of insulin, particularly for oral administration (Cahn et al., 2015). These advancements aim to provide more physiological insulin replacement and reduce the burden of diabetes management. 2.4 Alternate routes of insulin delivery Alternative routes of insulin delivery have been explored to improve patient compliance and reduce the invasiveness of insulin therapy. Inhaled insulin, such as the formulations used in the Exubera and Afrezza devices, has shown potential in fulfilling meal-related insulin requirements with a non-invasive approach (Owens et al., 2003; Flood, 2006). Despite initial setbacks, inhaled insulin remains a promising option if long-term safety and efficacy are confirmed (Owens et al., 2003; Flood, 2006). Oral insulin delivery has also been a focus of research, with advancements in formulation technologies, such as the use of surface-active substances and nanoparticle carriers, showing potential in overcoming the challenges of gastrointestinal degradation and poor bioavailability. Other routes, including intranasal and transdermal delivery, are being investigated, although they are not yet clinically viable (Sibiya et al., 2023). 3 Technological Advances in Insulin Therapy 3.1 Insulin Pumps Insulin pumps have revolutionized the management of type 1 diabetes by providing continuous subcutaneous insulin infusion (CSII). These devices offer a more flexible and precise method of insulin delivery compared to traditional injections, leading to improved glycemic control and quality of life for patients (Schaepelynck et al., 2011). Recent advancements include the development of patch pumps, which are smaller and more user-friendly, enhancing patient comfort and adherence. Additionally, the integration of insulin pumps with continuous glucose monitors (CGMs) has paved the way for more sophisticated automated insulin delivery systems (Schaepelynck et al., 2011). 3.2 Continuous glucose monitoring systems Continuous glucose monitoring (CGM) systems have significantly advanced over the past decade, providing real-time glucose readings and trends that help patients and healthcare providers make informed decisions about insulin therapy (Figure 1) (Beck et al., 2019; Yoo and Kim, 2023). CGMs have been shown to improve glycemic outcomes, particularly when combined with educational interventions (Yoo and Kim, 2023). The integration of
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