Peptides›Metabolic›Lixisenatide

Lixisenatide

/ Synthetic 44-residue exendin-4 analog; short-acting GLP-1 receptor agonist

TIER 1 · ClinicalN = 0 · TESTING PENDINGMW 4858.50 g·mol⁻¹

ALIAS · Adlyxin (trade — US) · Lyxumia (trade — EU) · AVE-0010

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Research use onlyAny dose figures below describe what specific cited studies used, reported factually. Nothing on this page is guidance for human use.READ FIRST →

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§ A · Identity

Primary sequenceHGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPSKKKKKK-NH2

MW · 4858.50CLASS · Synthetic 44-residue exendin-4 analog; short-acting GLP-1 receptor agonistCATEGORY · Metabolic

Tier 1. FDA-approved 2016 (Adlyxin) for type 2 diabetes; EMA-approved 2013 (Lyxumia). Short-acting prandial GLP-1 receptor agonist with the GETGOAL Phase 3 program and the ELIXA cardiovascular outcomes trial.

§ B · Mechanism of action

Lixisenatide is a synthetic 44-amino-acid analog of exendin-4 with a C-terminal lysine extension and amidation that confer DPP-4 resistance and a plasma half-life of approximately three hours. The short half-life produces a pronounced prandial action: once-daily pre-meal subcutaneous dosing slows gastric emptying acutely and suppresses postprandial glucose excursions through GLP-1 receptor agonism on pancreatic beta cells (glucose-dependent insulin release) and alpha cells (glucagon suppression). The pharmacokinetic profile distinguishes lixisenatide from long-acting GLP-1 receptor agonists, which provide steadier 24-hour fasting glucose control with less prandial-specific effect.

§ C · Human clinical evidence

Tier 1. The GETGOAL Phase 3 program (Riddle, Ratner, and colleagues, 2013) evaluated lixisenatide across multiple T2D treatment positions including monotherapy, add-on to oral agents, and add-on to basal insulin. The ELIXA cardiovascular outcomes trial (Pfeffer and colleagues, NEJM 2015) randomised 6,068 participants with T2D and recent acute coronary syndrome to lixisenatide or placebo and demonstrated cardiovascular safety (non-inferiority for major adverse cardiovascular events) without superiority — the first published GLP-1 receptor agonist CVOT.

§ D · Primary literature

PubMed26630143Pfeffer MA et al. — Lixisenatide in patients with type 2 diabetes and acute coronary syndrome · The New England Journal of Medicine · human-phase-3-rctIn T2D with recent ACS, lixisenatide was non-inferior to placebo on the primary composite of CV death, MI, stroke, or hospitalisation for unstable angina; no superiority signal observed.Limitations: Specific high-risk post-ACS population; modest median follow-up (~25 months); short-acting GLP-1 RA may differ from long-acting agents in CV effects.2015

PubMed23628617Riddle MC et al. — Adding once-daily lixisenatide for type 2 diabetes inadequately controlled by established basal insulin: a 24-week, randomized, placebo-controlled comparison (GetGoal-L) · Diabetes Care · human-phase-3-rctLixisenatide added to established basal insulin (with or without metformin) reduced HbA1c by ~0.7% versus placebo over 24 weeks, with modest weight loss and increased symptomatic hypoglycaemia.Limitations: 24-week duration; placebo-controlled but limited active comparator data within the same trial.2013

§ F · Safety signal

Class GLP-1 receptor agonist adverse events: nausea, vomiting, diarrhoea, headache, and hypoglycaemia (when combined with sulfonylurea or insulin). Acute pancreatitis is a class concern. Lixisenatide-specific anti-drug antibodies were observed in approximately 70% of recipients but did not consistently affect efficacy. Medullary thyroid C-cell tumour signals from rodent toxicology drive the class boxed warning.

§ H · Regulatory status

Regulatory status

FDA status:: FDA-approved
Compounding:: Not eligible for compounding (approved, not in shortage)

§ I · Notable gaps and controversies

ELIXA was neutral on cardiovascular efficacy (non-inferior but not superior to placebo), in contrast to subsequent positive CVOTs for liraglutide (LEADER), semaglutide (SUSTAIN-6), and albiglutide (Harmony Outcomes). The neutral signal is interpreted by some as a property of short-acting prandial GLP-1 agonism; others note ELIXA's specific population (acute coronary syndrome within 180 days) and follow-up. Sanofi de-emphasised lixisenatide commercially after the launch of iGlarLixi (insulin glargine plus lixisenatide fixed-ratio combination, Soliqua/Suliqua), and the standalone product has limited US uptake.