ArticleDiabetes2014
Novel PEGylated basal insulin LY2605541 has a preferential hepatic effect on glucose metabolism.
Article in Diabetes, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- Major adverse cardiovascular events with basal insulin peglispro versus comparator insulins in patients with type 1 or type 2 diabetes: a meta-analysis.Cardiovascular diabetology · 2016Pooled it
- The PNPLA3 I148M variant is associated with transaminase elevations in type 2 diabetes patients treated with basal insulin peglispro.The pharmacogenomics journal · 2018Trial
- Dose Unit Establishment for a New Basal Insulin Using Joint Modeling of Insulin Dose and Glycemic Response.Journal of diabetes science and technology · 2018Trial
- Basal insulin peglispro versus insulin glargine in insulin-naïve type 2 diabetes: IMAGINE 2 randomized trial.Diabetes, obesity & metabolism · 2016Trial
- Randomized, double-blind clinical trial comparing basal insulin peglispro and insulin glargine, in combination with prandial insulin lispro, in patients with type 1 diabetes: IMAGINE 3.Diabetes, obesity & metabolism · 2016Trial
- Randomized double-blind clinical trial comparing basal insulin peglispro and insulin glargine, in combination with prandial insulin lispro, in patients with type 2 diabetes: IMAGINE 4.Diabetes, obesity & metabolism · 2016Trial
- Better glycemic control and weight loss with the novel long-acting basal insulin LY2605541 compared with insulin glargine in type 1 diabetes: a randomized, crossover study.Diabetes care · 2013Trial
- A randomized, controlled study of once-daily LY2605541, a novel long-acting basal insulin, versus insulin glargine in basal insulin-treated patients with type 2 diabetes.Diabetes care · 2012Trial
- Insulin Analogs and the Mode of Insulin Delivery: Recent Advances and Challenges.Current pharmaceutical biotechnology · 2025Review
- The Basis for Weekly Insulin Therapy: Evolving Evidence With Insulin Icodec and Insulin Efsitora Alfa.Endocrine reviews · 2024Review
- Article
- Glucagon, cyclic AMP, and hepatic glucose mobilization: A half-century of uncertainty.Physiological reports · 2022Review
- New Horizons: Next-Generation Insulin Analogues: Structural Principles and Clinical Goals.The Journal of clinical endocrinology and metabolism · 2022Review
- Insulin-stimulated adipocytes secrete lactate to promote endothelial fatty acid uptake and transport.Journal of cell science · 2022Article
- Functionally selective signaling and broad metabolic benefits by novel insulin receptor partial agonists.Nature communications · 2022Article
- Structural principles of insulin formulation and analog design: A century of innovation.Molecular metabolism · 2021Review
- Brain insulin signalling in metabolic homeostasis and disease.Nature reviews. Endocrinology · 2021Review
- The Importance of the Mechanisms by Which Insulin Regulates Meal-Associated Liver Glucose Uptake in the Dog.Diabetes · 2021Article
- Engineering biopharmaceutical formulations to improve diabetes management.Science translational medicine · 2021Review
- The Peripheral Peril: Injected Insulin Induces Insulin Insensitivity in Type 1 Diabetes.Diabetes · 2020Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The impact of the novel basal insulin LY2605541 (LY) on hepatic and nonhepatic glucose uptake (non-HGU) was evaluated. Conscious dogs underwent euglycemic clamps with tracer and hepatic balance measurements. Clamp period infusions were peripheral venous regular insulin (0.1 nmol ⋅ kg(-1) ⋅ h(-1) [control], n = 6) or LY (bolus [nmol/kg], continuous [nmol ⋅ kg(-1) ⋅ h(-1)]: 0.5, 0.5 [n = 6]; 0.375, 0.375 [n = 5]; 0.25, 0.25 [n = 4]), somatostatin, and glucose, as well as intraportal glucagon (basal). During the clamp, the dogs switched from net hepatic glucose output to uptake (rates reached 2.1 ± 1.2, 0.9 ± 2.1, 8.6 ± 2.3, and 6.0 ± 1.1 µmol ⋅ kg(-1) ⋅ min(-1) within 5 h in control, LY0.25, LY0.375, and LY0.5, respectively). Non-HGU in LY increased less than in control; the ratio of change from basal in non-HGU to change in net hepatic glucose balance, calculated when glucose infusion rates (GIRs) were ~20 µmol ⋅ kg(-1) ⋅ min(-1) in all groups, was higher in control (1.17 ± 0.38) versus LY0.25 (0.39 ± 0.33), LY0.375 (-0.01 ± 0.13), and LY0.5 (-0.09 ± 0.07). Likewise, the change from baseline in glucose Rd-to-Ra ratio was greatest in control (1.4 ± 0.3 vs. 0.6 ± 0.4, 0.5 ± 0.2, and 0.6 ± 0.2 in LY0.25, LY0.375, and LY0.5, respectively). In contrast to exogenously administered human insulin, LY demonstrated preferential hepatic effects, similar to endogenously secreted insulin. Therefore, the analog might reduce complications associated with current insulin therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.