Once-Weekly Basal Insulin Shows Promise

Research into icodec, a new insulin analog with similar safety and efficacy as current long-acting insulins may help overcome clinical inertia. 

One of the oldest and best tools used in treating people living with diabetes is insulin, including those living with type 2 diabetes (T2D) whose blood glucose and A1c goals are unmet with other therapies. Despite today’s advances in the arsenal of various insulins available, many people living with diabetes are reluctant to use insulin due to fear of daily injections, among other justifiable concerns. Insulin icodec is derived from human insulin with three amino acid substitutions, a c20 icosane fatty diacid, and high albumin binding, which results in a geometric mean half-life of roughly 196 hours to allow for once-weekly injections. Previous studies among GLP-1 receptor agonists (another class of injectable diabetes medications) have shown that products that are once-weekly versus once or twice-daily have greater patient adherence and treatment satisfaction. Currently, there is no insulin product on the market that allows for once-weekly dosing. Insulin icodec may potentially help resolve some of the challenges patients living with T2D would face when it comes to starting basal insulin. 

A phase 2 trial by Rosenstock et al. was designed to compare the safety and efficacy of insulin icodec vs. insulin glargine 100 units/mL in combination with metformin with or without a DPP-4i in insulin-naïve patients with T2D. These patients are inadequately treated with their current therapy (A1c 7.0–9.5%). The trial was a randomized, double-blind, double-dummy, parallel-group, treat-to-target trial that included 247 adult patients. This study’s primary and secondary objectives were to assess the effect insulin icodec had on glycemic control and its safety and tolerability during the 26-week trial period, respectively. 

The estimated mean A1c at week 26 was 6.9% in the insulin glargine arm and 6.7% in the insulin icodec arm with a mean change in A1c from baseline of -1.15% and -1.33% (p=0.08), respectively. The estimated mean change from baseline to week 26 in fasting plasma glucose (FPG) was -54 mg/dL in the insulin glargine arm and -58 mg/dL in the insulin icodec arm with an estimated treatment difference (ETD) of -3.9 mg/dL [95% CI -11.9 – 4.2, p=0.34]. There was a statistically significant difference in favor of insulin icodec in the estimated mean change from baseline to week 26 in the 9-point self-measured blood glucose profile with a value of -7.9 mg/dL [95% CI -14.1 –1.6, p=0.01]. However, the authors noted that the study was not powered to determine a statistically significant difference in favor of one therapy over the other. The ETD (icodec/glargine) in mean change from baseline to week 26 in body weight was -0.08 kg [95% CI -1.08 – 0.93, p=0.88]. 

From a safety perspective, a negative binomial regression model (log link) was used to calculate an estimated rate ratio (ERR) of hypoglycemia events that were either clinically significant (<54 mg/dL) or severe (cognitive impairment requiring external assistance for recovery). An ERR (icodec/glargine) of 1.09 [95% CI 0.45 – 2.65, p=0.85] was obtained. Serious and severe adverse events of interest between both groups were similar, with no cardiovascular (CV) events being confirmed by adjudication. 

There is potential and a clear desire for once-weekly basal insulin injections such as insulin icodec in terms of improved patient adherence and the added convenience of avoiding daily injections. Further and larger-scale studies are needed to grasp better the magnitude of efficacy and safety data concerning longer treatment durations. While this promising therapy may not completely change the way patients living with diabetes feel about insulin injections, progress is being made in providing more patient-friendly options. 

Practice Pearls: 

• Insulin icodec is an investigational once-weekly basal insulin analog with similar efficacy (A1c, FPG, weight gain) and safety profile (hypoglycemic episodes) as once-daily insulin glargine 100 units/mL. 
• Insulin icodec may provide patients with diabetes a more attractive option for basal insulin over current therapies in terms of having to do fewer injections. 
• Further research is needed to determine the longer-term safety and efficacy data of insulin icodec. 

Nguyen, Hiep, et al. “Glucagon-Like Peptide-1 Receptor Agonist (GLP-1RA) Therapy Adherence for Patients with Type 2 Diabetes in a Medicare Population.“ Advances in therapy vol. 34,3 (2017): 658-673. doi:10.1007/s12325-016-0470-y 

Rosenstock, Julio, et al. “238-OR: Once-Weekly Basal Insulin Icodec Offers Comparable Efficacy and Safety vs. Once-Daily Insulin Glargine U100 in Insulin-Naïve Patients with T2D Inadequately Controlled on OADS.“ Diabetes, vol. 69, no. Supplement 1, 2020, doi:10.2337/db20-238-or. 

Lawand Kamal, PharmD Candidate 2021, Skaggs School of Pharmacy and Pharmaceutical Sciences 

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