Overview
Lixisenatide is a once-daily short-acting GLP-1 receptor agonist derived from exendin-4, modified at the C-terminus with deletion of one proline and addition of six lysine residues. FDA-approved in 2016 as Adlyxin (Sanofi), it distinguished itself from other GLP-1 agents through its pronounced postprandial glucose-lowering effect via potent gastric emptying inhibition. Lixisenatide was discontinued in the US market in January 2023.
Mechanism of action
Lixisenatide binds selectively and with high affinity to the GLP-1 receptor, a class B GPCR. Its C-terminal hexalysine extension confers DPP-4 resistance and receptor binding characteristics that differ from native GLP-1. Unlike long-acting GLP-1 agents, lixisenatide's short half-life (~3 hours) produces a pronounced and transient inhibition of gastric emptying concentrated around the postprandial period, making it particularly effective at blunting after-meal glucose spikes. Mechanistically, it stimulates glucose-dependent insulin secretion from beta cells via cAMP/PKA and PI3K/Akt pathways, suppresses glucagon from alpha cells, and activates hypothalamic GLP-1R to promote satiety. The acute gastric emptying effect is more pronounced than with longer-acting agents, explaining its differential glucose-lowering profile (more postprandial vs. fasting glucose effect).
Dosing protocols
| Purpose | Route | Dosage | Frequency | Notes |
|---|---|---|---|---|
| type 2 diabetes glycemic control | subcutaneous | 10–20 mcg | once daily | Start at 10 mcg once daily for 14 days, then increase to maintenance dose of 20 mcg once daily. Inject within 1 hour before the first meal of the day. |
| postprandial glucose control (add-on to basal insulin) | subcutaneous | 10–20 mcg | once daily | Same titration as monotherapy. Particularly studied as add-on to insulin glargine in GetGoal-Duo trials. Monitor for hypoglycemia and reduce insulin dose as needed. |
Dosing information is for educational purposes only. Consult a qualified healthcare professional before using any peptide.
Research summary
The GetGoal clinical program (12 pivotal trials) demonstrated HbA1c reductions of 0.7–1.0% and modest weight loss of 1–2 kg vs. placebo over 24 weeks. The ELIXA cardiovascular outcomes trial (6,068 patients, median 2.1 years) demonstrated cardiovascular safety (noninferiority) but not superiority for MACE vs. placebo — the first cardiovascular outcomes trial for any GLP-1 agonist, completed in 2015. Lixisenatide showed particular efficacy in controlling 2-hour postprandial glucose in combination with basal insulin.
Side effects
Side effects vary by individual. This is not an exhaustive list. Report unusual symptoms to a healthcare professional.
Common stacks
Peptides commonly paired with Lixisenatide for synergistic effects.
Legal status
FDA-approved July 2016. Voluntarily withdrawn from the US market by Sanofi effective January 1, 2023, due to commercial reasons (competition from newer GLP-1 agents). Still available in some international markets as Lyxumia. Was a Schedule-unscheduled prescription drug. No longer obtainable in the US through standard pharmacy channels.
Where to get it
Prescription required
Lixisenatide is a prescription medication. Consult your healthcare provider or a licensed telehealth platform for access.