Summary

Lixisenatide is a 44-amino-acid GLP-1 receptor agonist derived from exendin-4, modified with six C-terminal lysine residues. Approved by the EMA in 2013 (Lyxumia in Europe; Adlyxin in the US) for type 2 diabetes, lixisenatide is characterised by a strong effect on postprandial glucose excursions due to pronounced gastric emptying delay. It was evaluated in the ELIXA cardiovascular outcomes trial following acute coronary syndrome. This profile is for research and educational purposes only.

Mechanism

Lixisenatide is a potent agonist of the human GLP-1 receptor. Its mechanism of action includes: (1) glucose-dependent stimulation of insulin secretion from pancreatic beta cells; (2) glucose-dependent suppression of glucagon secretion; (3) pronounced slowing of gastric emptying — the latter effect is particularly strong with lixisenatide compared to other GLP-1 agonists, contributing to its distinctive postprandial glucose-lowering profile. Like other exendin-4 derivatives, lixisenatide is resistant to DPP-4 degradation, though it is cleared renally with a plasma half-life of approximately 3 hours, necessitating once-daily dosing.

Evidence base

Lixisenatide has a strong evidence base anchored by the 11-trial GetGoal programme (n>5,000) and the ELIXA cardiovascular outcomes trial (n=6,068). Glycaemic efficacy is well established, with a distinctive strength in postprandial glucose control. Cardiovascular safety was demonstrated but no benefit was shown. Weight loss is modest. The compound's clinical utility is well defined by over a decade of post-marketing experience.

Protocols

Lixisenatide is a licensed prescription medicine. In clinical practice, it is initiated at 10 mcg subcutaneously once daily for 14 days, then maintained at 20 mcg once daily before the first meal. These protocols are described for research reference only and do not constitute dosing advice.

Lixisenatide is classified as a Prescription-Only Medicine (POM) in the United Kingdom. Lyxumia is licensed by the MHRA. Supply without a prescription is unlawful. As a licensed medicine, sourcing lixisenatide from non-pharmacy research vendors carries significant counterfeit risk.

Vendor notes

Lixisenatide is a licensed POM available only through registered pharmacies with a valid prescription. We do not list research-grade vendors for this compound. Researchers requiring lixisenatide for in vitro or animal studies should source from established biochemical supply companies (e.g., Sigma-Aldrich, Tocris) with appropriate COAs.

References

  1. Ahrén B, Leguizamo Dimas A, Miossec P, et al. Efficacy and safety of lixisenatide once-daily morning or evening injections in type 2 diabetes inadequately controlled on metformin. Diabetes Care. 2013;36(9):2554–2561.
  2. Fonseca VA, Alvarado-Ruiz R, Raccah D, et al. Efficacy and safety of the once-daily GLP-1 receptor agonist lixisenatide in monotherapy. Diabetes Care. 2012;35(5):1225–1231.
  3. Pinget M, Goldenberg R, Niemoeller E, et al. Efficacy and safety of lixisenatide once daily versus placebo in type 2 diabetes insufficiently controlled on basal insulin. Diabetes Care. 2013;36(9):2472–2478.
  4. Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med. 2015;373(23):2247–2257.
  5. Rosenstock J, Aronson R, Grunberger G, et al. Benefits of LixiLan, a titratable fixed-ratio combination of insulin glargine plus lixisenatide. Diabetes Care. 2016;39(11):2026–2035.