The introduction of the ultra-long basal insulin icodec to the treatment of patients with Type 1 and Type 2 Diabetes, advantages and disadvantages. A Narrative Review.

Abstract

Background and aim
Insulin Icodec is a novel ultra-long-acting basal insulin generated by the Novo Nordisk company for the lifelong treatment of patients with diabetes type 1 and type 2. The series of ONWARDS 1-6 randomized controlled trials conducted in more than 80 countries showed that insulin icodec can maintain sufficient glycemic control at a lower frequency of injections (once weekly). The results of several clinical trials confirmed non-inferiority of insulin icodec as compared to the existing most prescribed insulins degludec and glargine, particularly in trial participants with diabetes type 2. Despite these undeniable advantages, insulin icodec provoked a higher number of hypoglycemia episodes, overall and severe ones. In addition to this, insulin icodec is a more expensive medicament comparing to degludec, detemir and glargine. The aim of this study is to investigate advantages and disadvantages of the treatment with insulin icodec versus degludec, glargine and GLP-1-agonist semaglutide in adult (18+) patients with type 1 and type 2 diabetes.

Methods
This study implemented narrative synthesis, inductive reasoning, visual representation and iterative process of discussion. The following electronic databases were searched: PubMed, Google Scholar and Clinicaltrials.gov to identify research studies conducted within 2016-2026 period. The search for the existing literature was limited to the studies (clinical trials, randomized controlled trials, original research articles) including available study protocols with a primary research data for the six predefined efficacy parameters: the level of glycated hemoglobin -HbA1c, fasting plasma glucose (FPG), change in diabetes treatment satisfaction (DTSQs) and safety parameters- the number of severe and overall episodes of hypoglycemia (blood glucose lower than 3,1mmol/l), body weight gain Cost-effectiveness was explored using data for quality-adjusted life-years (QALYs), increased life expectancy (LYs) , annual savings costs.

Findings
The results of six randomized controlled trials including insulin naive and experienced participants with type 2 diabetes demonstrated that insulin icodec is non-inferior to basal insulins degludec and glargine in terms of HbA1c, FPG levels reduction. Scores for a total treatment satisfaction were higher for insulin icodec in type 2 diabetes insulin naive and experienced groups. The results of ONWARDS 6 trial including participants with type 1 diabetes favoured a comparator -degludec, not icodec, in all predetermined efficacy and safety parameters. The main concern is an increased risk of overall and severe episodes of hypoglycaemia (twice higher on average versus comparators). The research findings for body weight gain demonstrated a slight increase for icodec, ranging from 0,89 to 2,77 kg to the end of trial period. According to cost-effectiveness, insulin icodec was more effective in terms of QALYs, life-years gained and annual savings than other long-acting comparators.

Conclusion
In conclusion, this narrative review found that insulin icodec might be a preferable treatment option for both insulin naive and experienced patients with type 2 diabetes. The main advantage is the ability to ensure optimal glycemic control at a lower frequency of injections. This positive feature may lead to better patients' adherence and more flexible treatment regimens. Also, when switching from oral glucose-lowering drugs to insulin therapy, patients may consider it as a less stressful regimen than those requiring daily injections. Additional benefits are a reduced risk of lipodystrophy, local pain and irritation. Higher cost-effectiveness can also be considered as an additional benefit due to the reduced quantity of needles required and additional QALYs, LYs gained. Among disadvantages, a higher risk of developing overall and severe episodes of hypoglycaemia in patients with type 1 and type 2 diabetes using bolus insulin as a supplement therapy; higher market cost and less availability can be outlined.