Trial reportDiabetes care2012
Plasma exposure to insulin glargine and its metabolites M1 and M2 after subcutaneous injection of therapeutic and supratherapeutic doses of glargine in subjects with type 1 diabetes.
Trial report in Diabetes care, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.
- Treatment with insulin (analogues) and breast cancer risk in diabetics; a systematic review and meta-analysis of in vitro, animal and human evidence.Breast cancer research : BCR · 2015Pooled it
- Trial
- Pharmacokinetic and pharmacodynamic bioequivalence of proposed biosimilar MYL-1501D with US and European insulin glargine formulations in patients with type 1 diabetes mellitus.Diabetes, obesity & metabolism · 2020Trial
- Single-dose euglycaemic clamp studies demonstrating pharmacokinetic and pharmacodynamic similarity between MK-1293 insulin glargine and originator insulin glargine (Lantus) in subjects with type 1 diabetes and healthy subjects.Diabetes, obesity & metabolism · 2018Trial
- Investigational new insulin glargine 300 U/ml has the same metabolism as insulin glargine 100 U/ml.Diabetes, obesity & metabolism · 2014Trial
- Trial
- The Silver Jubilee (2025) of Insulin Glargine: Introducing the Era of Long-Acting Insulin Analogues for Diabetes Mellitus.Diabetes, obesity & metabolism · 2026Review
- Effects of Different Exogenous Insulin Analog Treatments on the Evaluation of Pancreatic Islet Function in Diabetes.Journal of diabetes research · 2026Article
- The Modern Role of Basal Insulin in Advancing Therapy in People With Type 2 Diabetes.Diabetes care · 2025Review
- A comparative evaluation of bioequivalence of Gan & Lee glargine U300 and ToujeoFrontiers in endocrinology · 2024Article
- Pharmacokinetics and Safety of iGlarLixi in Healthy Chinese Participants: Results of a Phase 1 Randomized Study.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2023Article
- Assessment of circulating insulin using liquid chromatography-mass spectrometry during insulin glargine treatment in type 2 diabetes: Implications for estimating insulin sensitivity and β-cell function.Diabetes, obesity & metabolism · 2023 · on this mapArticle
- Assessing the Structural and Functional Similarity of Insulin Glargine Biosimilars.Journal of diabetes science and technology · 2023Article
- Insulin: evolution of insulin formulations and their application in clinical practice over 100 years.Acta diabetologica · 2022Review
- New Horizons: Next-Generation Insulin Analogues: Structural Principles and Clinical Goals.The Journal of clinical endocrinology and metabolism · 2022Review
- Pharmacokinetic and pharmacodynamic similarity evaluation between an insulin glargine biosimilar product and LantusFrontiers in pharmacology · 2022Article
- Current State and Principles of Basal Insulin Therapy in Type 2 Diabetes.Journal of clinical medicine research · 2022Review
- Detection of insulins in postmortem tissues: an optimized workflow based on immunopurification and LC-MS/HRMS detection.International journal of legal medicine · 2021Article
- Physicochemical and functional characterization of MYL-1501D, a proposed biosimilar to insulin glargine.PloS one · 2021Article
- Molecular Modeling and Bioinformatics Analysis of Drug-Receptor Interactions in the System Formed by Glargine, Its Metabolite M1, the Insulin Receptor, and the IGF1 Receptor.Bioinformatics and biology insights · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveIn vivo, after subcutaneous injection, insulin glargine (21(A)-Gly-31(B)-Arg-32(B)-Arg-human insulin) is enzymatically processed into 21(A)-Gly-human insulin (metabolite 1 [M1]). 21(A)-Gly-des-30(B)-Thr-human insulin (metabolite 2 [M2]) is also found. In vitro, glargine exhibits slightly higher affinity, whereas M1 and M2 exhibit lower affinity for IGF-1 receptor, as well as mitogenic properties, versus human insulin. The aim of the study was to quantitate plasma concentrations of glargine, M1, and M2 after subcutaneous injection of glargine in male type 1 diabetic subjects. RESEARCH DESIGN AND
methodsGlargine, M1, and M2 were determined in blood samples obtained from 12, 11, and 11 type 1 diabetic subjects who received single subcutaneous doses of 0.3, 0.6, or 1.2 units · kg(-1) glargine in a euglycemic clamp study. Glargine, M1, and M2 were extracted using immunoaffinity columns and quantified by a specific liquid chromatography-tandem mass spectrometry assay. Lower limit of quantification was 0.2 ng · mL(-1) (33 pmol · L(-1)) per analyte.
resultsPlasma M1 concentration increased with increasing dose; geometric mean (percent coefficient of variation) M1-area under the curve between time of dosing and 30 h after dosing (AUC(0-30h)) was 1,261 (66), 2,867 (35), and 4,693 (22) pmol · h · L(-1) at doses of 0.3, 0.6, and 1.2 units · kg(-1), respectively, and correlated with metabolic effect assessed as pharmacodynamics-AUC(0-30h) of the glucose infusion rate following glargine administration (r = 0.74; P < 0.01). Glargine and M2 were detectable in only one-third of subjects and at a few time points.
conclusionsAfter subcutaneous injection of glargine in male subjects with type 1 diabetes, exposure to glargine is marginal, if any, even at supratherapeutic doses. Glargine is rapidly and nearly completely processed to M1 (21(A)-Gly-human insulin), which mediates the metabolic effect of injected glargine.
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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.