The World's Longest-Acting Insulin Candidate in Diabetes Treatment: Insulin Icodec

What is insulin?

Insulin is a hormone produced by an organ called the pancreas. This hormone regulates the blood sugar (glucose) produced by the digestion of food, directing it to be used or stored in the body. Glucose is transported through the bloodstream to different body parts, mainly target areas such as muscle cells, fat cells, and liver cells. For glucose to enter cells and provide energy, insulin plays a crucial role by regulating the process. This mechanism is essential for controlling the body's energy production and basic functions.

In people with type 1 diabetes, the cells in the pancreas responsible for producing insulin are destroyed and the body cannot produce enough insulin. This condition requires insulin injections to enable the body to use glucose from food. In type 2 diabetes, insulin is produced, but the body does not respond effectively to the hormone. Therefore, some people with type 2 diabetes also need diabetes pills or insulin injections to use glucose from food effectively.

Types of Insulin

Insulin is administered subcutaneously. Different types of insulin injections have varying action profiles, such as rapid-acting, short-acting, intermediate-acting, and long-acting. Insulin therapy is customized to meet the patient's needs for both mealtime (bolus) and throughout the day (basal) to address insulin requirements. Short and rapid-acting insulins are used as bolus insulin. Intermediate, long-acting insulins are used as basal insulin.

Rapid-acting insulin: Usually administered just before a meal. The effect begins in about 15 minutes and lasts 2-4 hours—for example, insulin aspart, insulin glulisin, and insulin lispro.

Regular/short-acting insulin: Usually administered just before a meal. The effect begins in about 30 minutes and lasts 3-6 hours—for example, regular insulin.

Intermediate-acting insulin: Provides insulin for half a day or overnight. The effect begins in about 2-4 hours and lasts 12-18 hours—for example, NPH insulin.

Long-acting insulin: Provides insulin throughout the day. The effect begins in about 2 hours and lasts up to 24 hours—for example, insulin degludec, insulin detemir, and insulin glargine.

What is HbA1c?

The HbA1c test is used to diagnose diabetes or assess the effectiveness of a treatment plan. It is expressed as percentage (%) and indicates the average blood glucose levels over the past two to three months. Higher percentage values indicate higher blood glucose levels during that period. A1c level of 6.5% or higher is a diagnostic criterion for diabetes. For most patients being treated for diabetes, the goal is to achieve an A1c level of less than 7%.

What is insulin icodec?

Insulin Icodec is a basal insulin analog developed for weekly subcutaneous use in people with diabetes. It is designed for once-weekly use and has an average half-life of 196 hours, providing sustained glucose-lowering action throughout the week. People on insulin therapy often require complex insulin regimens with multiple daily injections. Reducing the number of basal insulin injections from 365 to 52 per year with insulin icodec represents a significant advance in insulin therapy management. This not only reduces the injection burden but also improves patient adherence, which is a substantial development in insulin therapy.

Efficacy and safety profile of insulin icodec

The insulin icodec has been evaluated in various phase 3 studies (ONWARDS 1-6) worldwide, comparing its efficacy and safety profile with other insulin types. The primary outcome measured in clinical trials was the percentage reduction in HbA1c levels. Additionally, the studies examined the rates of clinically significant or severe hypoglycemia. The ONWARDS 1, 3, and 5 studies demonstrated the superiority of insulin icodec over other long-acting insulins in patients who had not previously received insulin therapy. In the other studies, except ONWARDS-6, no significant difference was observed in clinically significant or severe hypoglycemia rates.

Insulin icodec vs. insulin glargine

The ONWARDS-1 clinical trial involved 984 patients with type 2 diabetes (not previously treated with insulin) and compared insulin icodec with once-daily long-acting insulin glargine and reported that at week 52, insulin icodec was superior to insulin glargine in reducing mean HbA1c levels (-1.55% vs. -1.35%). Furthermore, based on secondary outcomes reported at week 52, there was no statistically significant difference in the rates of severe or clinically significant hypoglycemia between the two groups.

Insulin icodec vs. insulin degludec

In the ONWARDS-2 clinical trial, which included 526 patients with type 2 diabetes (previously on insulin therapy), comparing insulin icodec with another long-acting insulin, insulin degludec, it was reported that at week 26, insulin icodec demonstrated superiority in reducing average HbA1c levels compared to insulin degludec (-0.93% vs. -0.71%). Additionally, based on secondary outcomes reported at week 31 in this study, there was no statistically significant difference in the rates of severe or clinically significant hypoglycemia between the two groups.

In the ONWARDS-6 clinical trial, the only study that included patients with type 1 diabetes, outcomes of patients receiving insulin icodec + insulin aspart were compared with those receiving insulin degludec + insulin aspart. The results showed similar outcomes in reducing HbA1c levels and glycemic control (-0.47% vs. -0.51%). However, with insulin icodec use, it was reported that the rates of clinically significant or severe hypoglycemia were 1.9 times higher compared to insulin degludec.

Drug approval by FDA

Insulin icodec has generally demonstrated a safe and well-tolerated profile in clinical studies. The decision regarding the approval of this medication is expected to be made by the U.S. Food and Drug Administration (FDA) in 2024.