Once-Weekly Insulin Therapies in Diabetes Management

Recent advances in insulin formulation have brought forth once-weekly therapies that promise improved adherence and consistent glycaemic control for people with diabetes. Traditional basal insulin requires daily injections, posing burdens that can lead to missed doses and erratic glucose levels. Once-weekly analogues are engineered to combine stabilised molecular structures, strong albumin-binding properties and modified receptor affinities to extend circulating half-lives to around seven days. This sustained delivery yields flatter pharmacokinetic and pharmacodynamic profiles, reducing peaks and troughs in insulin action. Clinical programmes have demonstrated that weekly insulin therapies achieve comparable reductions in glycated haemoglobin (HbA1c) to daily regimens while maintaining acceptable hypoglycaemia risk. These formulations are poised to simplify treatment paradigms, enhance quality of life and address global challenges in diabetes care by supporting persistence and adherence across diverse populations.

Research from Nature Portfolio

One study elucidated the role of thiol–disulphide exchange in insulin clearance and demonstrated that strategic substitution in a weekly analogue significantly stabilises disulphide bonds, contributing to a half-life of approximately seven days. This mechanistic insight underpins the design principles for prolonging insulin action. Another investigation described the molecular engineering of ultra-long basal insulin analogues for oral administration. By lowering receptor affinity 500-fold and employing robust albumin-binding moieties, these compounds achieved elimination half-lives exceeding 70 hours in humans and minimised variability in plasma exposure. Although delivered orally, this platform offers a blueprint for injectable weekly insulins through similar pharmacokinetic optimisation.

Once-Weekly Insulin Therapies in Diabetes Management publication trend

The graph below shows the total number of articles in once-weekly insulin therapies in diabetes management across all publications each year (not limited to Nature Index journals).

Technical terms

Basal insulin: Long-acting formulation providing baseline insulin levels between meals.

Pharmacokinetics: Study of drug absorption, distribution, metabolism and excretion over time.

Pharmacodynamics: Examination of a drug’s biological effects and mechanism of action.

Albumin-binding: Reversible interaction of drug molecules with serum albumin to prolong circulation.

Thiol–disulphide exchange: Chemical reaction altering disulphide bonds that can influence protein degradation.

References

1. The Basis for Weekly Insulin Therapy: Evolving Evidence With Insulin Icodec and Insulin Efsitora Alfa. Endocrine Reviews (2024).
2. Enhanced disulphide bond stability contributes to the once-weekly profile of insulin icodec. Nature Communications (2024).
3. Once-weekly insulin icodec versus once-daily insulin degludec as part of a basal-bolus regimen in individuals with type 1 diabetes (ONWARDS 6): a phase 3a, randomised, open-label, treat-to-target trial. The Lancet (2023).
4. Molecular engineering of safe and efficacious oral basal insulin. Nature Communications (2020).
5. Once-Weekly Insulin Icodec vs. Once-Daily Insulin Glargine U100 for type 2 diabetes: a systematic review and meta-analysis of phase 2 randomized controlled trials. Archives of Endocrinology and Metabolism (2023).