LixisenatidevsExenatide

Molecular Formula

C₂₁₅H₃₄₇N₆₁O₆₅S

Molecular Weight

4,858 Da

Half-Life

2.8-3 hours

Bioavailability

55% subcutaneous bioavailability

CAS Number

320367-13-3

Molecular Formula

C₁₈₄H₂₈₂N₅₀O₆₀S

Molecular Weight

4,187 Da

Half-Life

Byetta: ~2.4 hours (immediate-release); Bydureon: ~7 weeks effective duration via PLGA microsphere technology; Tmax ~2.1 hours (Byetta)

Bioavailability

65–75% after subcutaneous injection (Byetta); microsphere sustained release for Bydureon

CAS Number

183321-74-6

Common

• Nausea
• Vomiting
• Diarrhea
• Headache

Uncommon

• Injection Site Reactions

Serious

• Acute Pancreatitis

Common

• Nausea
• Vomiting and diarrhea
• Injection site nodules (Bydureon)
• Decreased appetite and constipation

Uncommon

• Hypoglycemia

Serious

• Acute pancreatitis
• Renal impairment

Evidence Level

Strong human trials (Phase 3 or FDA approved)

FDA Status

FDA approved for this use

Safety Overview

Lixisenatide (Lyxumia, Adlyxin) is an FDA and EMA-approved GLP-1 receptor agonist with safety data from Phase 3 trials (LEAD program, 2012-2013) involving 4,000+ patients with type 2 diabetes. Gastrointestinal side effects (nausea, vomiting) are most common during dose escalation (30-40% of patients) but typically resolve after 2-3 weeks of stable dosing. The short half-life (3 hours) compared to longer-acting GLP-1 agonists means side effects have rapid onset and offset. No serious adverse events exceed background diabetes population rates in pivotal trials.

Contraindications

• xKnown hypersensitivity to lixisenatide or excipients
• xPersonal or family history of medullary thyroid carcinoma
• xPatients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
• xSevere gastrointestinal disease including gastroparesis

Evidence Level

Strong human trials (Phase 3 or FDA approved)

FDA Status

FDA approved for this use

Safety Overview

Exenatide is an FDA-approved GLP-1 receptor agonist with post-market safety data spanning 15+ years, though some safety concerns have emerged. Nausea affects 30-45% of patients, dose-dependent and typically improves within 1-2 weeks but can lead to treatment discontinuation in 5% of patients. Pancreatitis risk, while rare (0.1-0.2%), is increased and contraindicated in patients with history of acute pancreatitis. Thyroid C-cell tumor risk identified in rodent studies supports clinical vigilance in patients with personal or family history of medullary thyroid cancer (MTC) or multiple endocrine neoplasia type 2—absolute contraindication. Acute kidney injury has been reported in 0.3-1% of patients, particularly with concurrent NSAID or ACE inhibitor use. Hypoglycemia risk is minimal when used as monotherapy but increases substantially when combined with insulin or sulfonylureas.

Contraindications

• xPersonal or family history of medullary thyroid carcinoma (MTC) — black box warning based on animal data
• xMultiple Endocrine Neoplasia syndrome type 2 (MEN 2)
• xPrior serious hypersensitivity reaction to exenatide or any excipient
• xSevere renal impairment (eGFR <15 mL/min) or end-stage renal disease