Insulin peglispro

Long Acting Insulin Analog (PEGylated)Rx: InvestigationalCompound: Withdrawn

Also known as: Basal Insulin Peglispro, BIL, Insulin peglispro, LY2605541, PEGylated insulin lispro

Educational Only — Not medical advice. Consult a qualified clinician before using any peptide.

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Summary

Insulin peglispro (BIL) is an investigational, PEGylated basal insulin analogue administered by subcutaneous injection. It is designed to provide a flat, prolonged insulin action with a preferential effect on the liver, aiming to improve glycaemic control in adults with type 1 or type 2 diabetes.

Mechanism of Action

Pegylation of the insulin lispro molecule reduces its peripheral tissue activity and prolongs its circulation time, creating a flat, long‑lasting basal profile. This modification shifts the insulin action toward the liver (hepato‑preferential), mimicking physiological basal insulin secretion while limiting peripheral glucose uptake, which contributes to lower fasting glucose and reduced nocturnal hypoglycaemia.

What the Research Shows

Phase 3 IMAGINE trials (over 6,000 participants) compared BIL with insulin glargine or NPH in both type 1 and type 2 diabetes. Across studies, BIL achieved greater reductions in HbA1c (0.2–0.8% superiority), lower fasting glucose, reduced glucose variability, and less nocturnal hypoglycaemia. Weight loss was observed in type 1 patients, and less weight gain in type 2 patients. However, BIL was associated with higher triglycerides, alanine aminotransferase, liver fat, and more injection‑site reactions. A meta‑analysis of seven trials found no increase in major cardiovascular events (hazard ratio ~0.8).

Reported Benefits

Clinical trials consistently showed that BIL lowers HbA1c more than glargine, reduces nocturnal hypoglycaemia, and provides a flatter glucose profile. In type 1 diabetes it can promote modest weight loss, and in type 2 diabetes it limits weight gain. The hepato‑preferential action may contribute to these metabolic advantages.

Limitations of the Evidence

BIL increases daytime and total hypoglycaemia in some studies, raises triglycerides, ALT, and liver fat, and leads to more injection‑site reactions. Long‑term safety beyond 78 weeks is not established, and the compound remains investigational with no regulatory approval. Cardiovascular safety appears comparable, but data are limited to trial populations.

Safety Considerations

Adverse effects reported include higher serum triglycerides, elevated alanine aminotransferase, increased liver fat, and injection‑site reactions such as lipohypertrophy. While nocturnal hypoglycaemia is reduced, daytime hypoglycaemia may be higher. No excess in major cardiovascular events was observed in pooled analyses, but clinicians should monitor liver enzymes, lipid profiles, and injection sites during use.

How It Is Administered

Insulin peglispro is given as a once‑daily subcutaneous injection, typically at bedtime, as part of a basal‑bolus regimen with rapid‑acting insulin for meals. Formulations are supplied in a pre‑filled syringe or pen for subcutaneous delivery.

Routes of Administration

Subcutaneous

Goals & Uses

  • Weight neutral profileMetabolicLow
  • Weight management in insulin-treated diabetesMetabolic / EndocrineLow
  • Glycemic controlDiabetesModerate
  • Reduced nocturnal hypoglycemiaSafetyModerate
  • Basal glycemic controlDiabetes ManagementModerate
  • Reduction of nocturnal hypoglycemiaSafety / TolerabilityModerate
  • Glycemic control in type 2 diabetesMetabolicModerate
  • Glycemic control in type 1 diabetesMetabolic / EndocrineModerate

Contraindications

  • Severe hypoglycemiaMetabolicHigh
  • Hypersensitivity to insulin peglispro or PEG excipientsImmunologicHigh
  • Hypersensitivity to insulin or PEGAllergyHigh
  • Pre-existing hepatic diseaseHepaticHigh
  • Active liver diseaseHepaticModerate

Adverse Effects

  • Increased hepatic fat (steatosis)HepaticUncommon
  • HypoglycemiaMetabolicCommonAbnormally low blood glucose
  • Injection site reactionsLocalUncommon
  • Hepatic steatosis (increased liver fat content)HepaticCommon
  • Increased triglyceridesLipidUncommon
  • Triglyceride elevationMetabolicUncommon
  • Elevated liver enzymes (ALT/AST)HepaticCommon
  • Injection‑site reactionsLocalCommon
  • LipohypertrophyDermatologicUncommon
  • Weight gainMetabolicCommonIncrease in body weight
  • Elevated liver enzymesHepaticUncommonIncrease in AST/ALT or other hepatic markers

Drug Interactions

  • Beta‑blockersModerate
  • Beta-blockersModerate
  • CorticosteroidsModerate
  • Other insulinsHigh
  • Other insulin productsHigh
  • Oral antidiabetic agentsModerate
  • SulfonylureasModerateMay increase risk of low blood sugar
  • Hepatotoxic drugsHigh

Population Constraints

  • PregnancyReproductive SafetyRelative
  • Patients with hepatic impairment or liver diseaseHepaticAbsolute
  • Elderly with renal impairmentRenalRelative
  • Pediatric patientsAgeAbsolute
  • Pregnant womenReproductiveRelative
  • Pediatrics (<2 years)AgeAbsolute
  • Patients with hypertriglyceridemiaMetabolicRelative

Regulatory Status

  • European UnionUnapprovedNo marketing authorization; withdrawn from development.
  • United StatesUnapprovedInvestigational; development discontinued.
  • United KingdomUnapprovedNever submitted for approval; development halted.

Development discontinued in 2015; no approvals in US, EU, or UK.

Evidence & Sources

Frequently Asked Questions

How does insulin peglispro differ from standard basal insulins?

BIL is PEGylated, which prolongs its action and reduces peripheral activity, creating a liver‑focused (hepato‑preferential) insulin effect. This results in a flatter glucose profile, less nocturnal hypoglycaemia, and modest weight benefits compared with insulin glargine or NPH.

Is insulin peglispro approved for clinical use?

No. Insulin peglispro remains investigational and has not received regulatory approval for any indication.

What are the main safety concerns with insulin peglispro?

Clinical studies reported higher triglycerides, elevated liver enzymes (ALT), increased liver fat, and more injection‑site reactions. While major cardiovascular events were not increased, daytime hypoglycaemia may be higher, so monitoring is advised.

Can insulin peglispro be used in both type 1 and type 2 diabetes?

Trials have evaluated BIL in adults with both type 1 and type 2 diabetes, showing efficacy in lowering HbA1c in each group. However, the safety profile differs slightly, with weight loss seen in type 1 and less weight gain in type 2.

How is dosing of insulin peglispro determined?

Dosing is individualized and titrated to achieve target fasting glucose, similar to other basal insulins. In studies, patients received a bedtime injection as part of a basal‑bolus regimen, with basal doses generally higher than with glargine.

What is Insulin peglispro?

Insulin peglispro (BIL) is an investigational, PEGylated basal insulin analogue administered by subcutaneous injection. It is designed to provide a flat, prolonged insulin action with a preferential effect on the liver, aiming to improve glycaemic control in adults with type 1 or type 2 diabetes.

What is Insulin peglispro used for?

Insulin peglispro is educationally associated with: Weight neutral profile, Weight management in insulin-treated diabetes, Glycemic control, Reduced nocturnal hypoglycemia, Basal glycemic control, Reduction of nocturnal hypoglycemia, Glycemic control in type 2 diabetes, Glycemic control in type 1 diabetes. Educational only — not medical advice.

How is Insulin peglispro administered?

Recorded routes of administration: Subcutaneous.

What are the potential side effects of Insulin peglispro?

Reported adverse effects include: Increased hepatic fat (steatosis), Hypoglycemia, Injection site reactions, Hepatic steatosis (increased liver fat content), Increased triglycerides, Triglyceride elevation, Elevated liver enzymes (ALT/AST), Injection‑site reactions, Lipohypertrophy, Weight gain, Elevated liver enzymes. This list is not exhaustive — consult a qualified clinician.

Who should avoid Insulin peglispro?

Recorded contraindications: Severe hypoglycemia, Hypersensitivity to insulin peglispro or PEG excipients, Hypersensitivity to insulin or PEG, Pre-existing hepatic disease, Active liver disease. Consult a qualified clinician before use.

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