Once-weekly basal insulin icodec: Looking ONWARDS from pharmacology to clinical trials

Background and aims: Insulin icodec is currently the most advanced candidate insulin suitable for once-weekly administration. We aim to conduct a systematic review of the literature to find out the efficacy and safety of insulin icodec in patients with diabetes mellitus.

Methods: We systematically searched the electronic database of PubMed, and Google Scholar from inception until August 20, 2022, using MeSH keywords. Ongoing trials of insulin icodec were additionally searched from the ClinicalTrials.Gov. We retrieved all the available granular details of phase 1 to phase 3 studies of insulin icodec in both type 1 and type 2 diabetes.

Results: Phase 1 study showed insulin icodec having a half-life of 196 h (>1 week) while a steady state is achieved after 3 to 4 weekly injections. Phase 2 studies compared once-weekly icodec to insulin glargine (U-100) and found a similar glucose control with no significantly greater hypoglycemia risks. Top-line results from the five phase 3 studies reported better glucose control with once-weekly icodec compared to both once-daily insulin glargine (ONWARDS 1) and once-daily degludec (in both ONWARDS 2 and 4) with similar rates of hypoglycemia in type 2 diabetes, although there was a higher hypoglycemic event with insulin icodec in type 1 diabetes (ONWARDS 6) compared to once-daily degludec despite a similar glycemic control.

Conclusion: A brighter prospect of once-weekly insulin icodec is on the card in particular in type 2 diabetes in terms of reducing injection pricks by >85% vs. once-daily basal insulin analogs, although few unknowns still exist.