## 4 Treatment Advancements
### Diabetes Treatments  
The discovery of insulin stands as a landmark achievement in the history of medicine, revolutionizing the treatment of diabetes. In the early 1900s, [PERSON], a Romanian physiologist, conducted pioneering research on the pancreas. His work included isolating an extract with antidiabetic properties from the pancreas, which he called \"pancreine\" [77; 78]. This crucial insight paved the way for subsequent advancements. Building upon this foundation, [PERSON]'s successful isolation and clinical application of insulin in 1921 marked a pivotal moment in diabetes management [79]. This groundbreaking discovery continues to shape diabetes management today. While advancements in insulin delivery methods and formulations have occurred since the initial discovery, the core principle of insulin therapy remains a cornerstone of diabetes treatment. The legacy of insulin's discovery extends far beyond its immediate impact, paving the way for ongoing research and the development of novel therapeutic approaches for diabetes. **Advancements in the insulin field:** Traditional insulin formulations like regular and neutral protamine Hagedorn (NPH) insulin provided the initial foundation for diabetes management, offering control through varying onsets and durations of action. However, limitations like peak action mismatch for regular insulin and absorption variability for NPH insulin necessitated further advancements. The rise of newer insulin molecules addressed these concerns [80; 81]. Rapid-acting analogs like ispro and glulisine mimic natural insulin release with a faster onset and shorter duration, ideal for postprandial control [82; 83]. Short-acting analogs like aspart offer quicker action than regular insulin for pre-meal injections while minimizing hypoglycemia risk with their shorter duration [84; 85]. Intermediate-acting analogs like glargine provide consistent, sustained release throughout the day, improving overall glycemic control [86; 87]. Long-acting analogs like detemir or second-generation basal insulin, degludec, offer continuous basal insulin with extended durations, simplifying treatment regimens [88; 89]. The relentless pursuit of improved glycemic control in diabetes management has driven the development of ever-longer-acting insulins. Following the success of intermediate-acting analogs like glargine, a new class of ultra-long-acting insulins has emerged. These insulins boast extended durations of action, potentially exceeding 40 h, and offer the promise of simplified treatment regimens with less frequent injections. The once-weekly insulin iodec exemplifies this advancement, offering a potential alternative to daily injections for both type 1 [90] and type 2 diabetes [91]. The phase three ONWARDS trials investigated the efficacy and safety of once-weekly icodec compared to daily degludec injections for both type 1 and type 2 diabetes [92]. The studies found that icodec was as effective, or even more effective, in reducing HbA1c levels compared to degludec. Additionally, icodec may improve treatment adherence due to the reduced injection frequency [93]. However, some limitations exist, including a slightly increased risk of hypoglycemia with icodec and a lack of long-term data on its safety and efficacy [90]. **The future of insulin:** While injectable insulin remains the mainstay of treatment for diabetes, it is not without its challenges. The risk of hypoglycemia and the need for strict adherence to daily injections can be significant disadvantages for many patients. Despite these issues, the quest for a convenient and non-invasive alternative continues. Oral insulin delivery has long been a coveted goal, and exciting research is exploring several promising avenues. _Sublingual Drops:_ Researchers at the University of British Columbia are developing fast-acting oral insulin drops that dissolve under the tongue.