Insulin peglispro

Summary

Insulin peglispro (BIL) is a novel PEGylated basal insulin analogue developed by Eli Lilly. It demonstrated a flatter, longer-lasting glucose-lowering profile than insulin glargine in clinical trials, with potentially better glycemic control and less nocturnal hypoglycemia. However, development was discontinued in 2015 due to hepatic safety signals (elevated liver enzymes and liver fat accumulation) observed in Phase III trials.

Mechanism of Action

Insulin peglispro is a long-acting basal insulin analogue conjugated with a large polyethylene glycol (PEG) moiety at the B29 lysine residue. The PEG chain increases hydrodynamic size, slowing absorption from the subcutaneous depot and reducing receptor-mediated clearance, resulting in a flat, prolonged pharmacokinetic and pharmacodynamic profile. It activates insulin receptors to lower blood glucose via enhanced glucose uptake in peripheral tissues and suppression of hepatic glucose output, with preferential hepatic action due to its physicochemical properties.

Routes of Administration

Goals & Uses

• Weight management in insulin-treated diabetesMetabolic / EndocrineLow
• Reduction of nocturnal hypoglycemiaSafety / TolerabilityModerate
• Glycemic control in type 2 diabetesMetabolicModerate
• Glycemic control in type 1 diabetesMetabolic / EndocrineModerate

Contraindications

• Hypersensitivity to insulin peglispro or PEG excipientsImmunologicHigh
• Pre-existing hepatic diseaseHepaticHigh

Adverse Effects

• HypoglycemiaMetabolicCommonAbnormally low blood glucose
• Injection site reactionsLocalUncommon
• Hepatic steatosis (increased liver fat content)HepaticCommon
• Triglyceride elevationMetabolicUncommon
• Elevated liver enzymes (ALT/AST)HepaticCommon
• LipohypertrophyDermatologicUncommon

Drug Interactions

• Beta-blockersModerate
• CorticosteroidsModerate
• Oral antidiabetic agentsModerate
• Hepatotoxic drugsHigh

Population Constraints

• Patients with hepatic impairment or liver diseaseHepaticAbsolute
• Pediatric patientsAgeRelative
• Pregnant womenReproductiveRelative
• Patients with hypertriglyceridemiaMetabolicRelative

Regulatory Status

• European UnionInvestigationalNo marketing authorization application filed. Development halted globally in 2015.
• United StatesInvestigationalDevelopment discontinued by Eli Lilly in 2015 following FDA concerns about hepatic safety findings in Phase III trials. No NDA submitted.
• United KingdomInvestigationalNot approved or submitted for approval; development discontinued prior to any regulatory submission.

Eli Lilly discontinued development of insulin peglispro in August 2015 after regulatory agencies and the FDA raised concerns regarding hepatic findings (elevated alanine aminotransferase, increased liver fat content) in Phase III IMAGINE trials. No regulatory submission for approval was made in any jurisdiction.

Evidence & Sources

No sources recorded yet.