Evidence map›Paper›PMID 30593607›Full record

Trial reportDiabetologia2019

Randomised, phase 1, dose-finding study of MEDI4166, a PCSK9 antibody and GLP-1 analogue fusion molecule, in overweight or obese patients with type 2 diabetes mellitus.

Meena Jain, Glenn Carlson, William Cook, Linda Morrow, Marcella Petrone, Nicholas E White, Tao Wang, Jacqueline Naylor, Philip Ambery, Charles Lee and 1 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Diabetologia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02524782 (A Phase 1, Combined Single- and Multiple-ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics), which is not on this map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.3field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

NCT02524782 phase1completednot on this map

A Phase 1, Combined Single- and Multiple-ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of MEDI4166 in Subjects With Type 2 Diabetes Mellitus (T2D)

TypeinterventionalSponsorMedImmune LLCRan2015 to 2017Enrolled103ConditionsType 2 DiabetesArmsMEDI-4166, Placebo
3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
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  6. Glucagon-like peptide 1 (GLP-1).Molecular metabolism · 2019 · on this map
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Meena JainMedImmune Ltd, Milstein Building, Granta Park, Cambridge, CB21 6GH, UK. JainM@MedImmune.com.
Glenn CarlsonAstraZeneca, Gaithersburg, MD, USA.
William CookMedImmune, Gaithersburg, MD, USA.
Linda MorrowProSciento Inc., Chula Vista, CA, USA.
Marcella PetroneMedImmune Ltd, Milstein Building, Granta Park, Cambridge, CB21 6GH, UK.
Nicholas E WhiteMedImmune Ltd, Milstein Building, Granta Park, Cambridge, CB21 6GH, UK.
Tao WangMedImmune, Gaithersburg, MD, USA.
Jacqueline NaylorMedImmune Ltd, Milstein Building, Granta Park, Cambridge, CB21 6GH, UK.
Philip AmberyMedImmune Ltd, Milstein Building, Granta Park, Cambridge, CB21 6GH, UK.
Charles LeeMedImmune, Gaithersburg, MD, USA.
Boaz HirshbergMedImmune, Gaithersburg, MD, USA.
AstraZeneca (United States) · USPrecision Research Institute · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aims/hypothesisCardiovascular disease is the leading cause of morbidity and mortality in people with type 2 diabetes. MEDI4166 is a proprotein convertase subtilisin/kexin type 9 (PCSK9) antibody and glucagon-like peptide-1 (GLP-1) analogue fusion molecule designed to treat patients with type 2 diabetes who are at risk for cardiovascular disease. In this completed, first-in-human study, we evaluated the safety and efficacy of single or multiple doses of MEDI4166 in participants with type 2 diabetes.

methodsIn this phase 1 study that was conducted across 11 clinics in the USA, eligible adults had type 2 diabetes, a BMI of ≥25 kg/m

resultsMEDI4166 or placebo was administered to n = 30 or n = 10 participants, respectively, in Part A of the study, and n = 48 or n = 15 participants, respectively, in Part B. The incidence of treatment-emergent adverse events (TEAEs) were comparable between MEDI4166 and placebo in both Part A (60% vs 50%) and Part B (79% vs 87%) of the study. Common TEAEs with MEDI4166 included injection-site reactions, diarrhoea and headache; there was no evidence for dose-related increases in TEAEs. In Part B of the study, at all tested doses of MEDI4166, there was a significant decrease in LDL-cholesterol levels vs placebo (least squares mean [95% CI]; MEDI4166 50 mg, -1.25 [-1.66, -0.84]; MEDI4166 200 mg, -1.97 [-2.26, -1.68]; MEDI4166 400 mg, -1.96 [-2.23, -1.70]; placebo, -0.03 [-0.35, 0.28]; all p < 0.0001). However, there were no clinically relevant reductions or significant differences between MEDI4166 vs placebo in glucose AUC CONCLUSIONS/

interpretationMEDI4166 was associated with an acceptable tolerability profile and significantly decreased LDL-cholesterol levels in a dose-dependent manner in overweight or obese patients with type 2 diabetes. However, there were no significant reductions in postprandial glucose levels at any dose of MEDI4166.

trial registrationClinicalTrials.gov NCT02524782

fundingThis study was funded by MedImmune LLC, Gaithersburg, MD, USA.

Indexed as

AntibodiesDiabetes Mellitus, Type 2Double-Blind MethodFemaleHumansHypoglycemic AgentsMaleMiddle AgedObesityOverweightProprotein Convertase 9Treatment OutcomeAntibodiesHypoglycemic AgentsPCSK9 protein, humanProprotein Convertase 9First-in-human studyGlucagon-like peptide-1 analogueGlucoseLow-density lipoprotein cholesterolMultiple ascending dosePharmacokineticsPhase 1Proprotein convertase subtilisin/kexin type 9 antibodySingle ascending doseType 2 diabetes mellitus

Identifiers

PMID30593607
OpenAlexW2908362502

What Socratic holds

Texttitle and abstract
Read underepoch 390

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 Socratic graph.