Evidence mapPaperPMID 30938764Full record

Trial reportThe Journal of clinical endocrinology and metabolism2019

Metformin Improves Peripheral Insulin Sensitivity in Youth With Type 1 Diabetes.

Melanie Cree-Green, Bryan C Bergman, Eda Cengiz, Larry A Fox, Tamara S Hannon, Kellee Miller, Brandon Nathan, Laura Pyle, Darcy Kahn, Michael Tansey and 4 more

Registry-linked trialOpen access · bronzeAbstract readMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in The Journal of clinical endocrinology and metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT02045290. Cited by 66 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed, 3 pooled it
8.4field-weighted citation impact, top 2% 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.

NCT02045290 phase3completed

Metformin Therapy for Overweight Adolescents With Type 1 Diabetes (T1D)--Insulin Clamp Ancillary Study for Assessment of Insulin Resistance

Ran2014Enrolled37Registered outcomes3Posted comparisons0ConditionsType 1 DiabetesArmsMetformin, Placebo
Open the trial in the graph
3 · Its place in the literature

Who cites it

66 citing papers in PubMed, 3 syntheses or guidelines pooled it, 95 citations in OpenAlex.

  1. Pooled it
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  11. Precision and accuracy of hyperglycemic clamps in a multicenter study.American journal of physiology. Endocrinology and metabolism · 2021
    Trial
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  18. Islet Tissue Macrophages in Immunity Homeostasis and Type 1 Diabetes.Clinical reviews in allergy & immunology · 2025
    Review
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6 more citing papers are in PubMed but not listed here.

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

14 authors at 9 institutions in 1 country.

Melanie Cree-GreenDivision of Pediatric Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Bryan C BergmanDivision of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Eda CengizYale School of Medicine University, New Haven, Connecticut.
Larry A FoxNemours Children's Specialty Care, Jacksonville, Florida.
Tamara S HannonDivision of Pediatric Endocrinology and Diabetology, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana.
Kellee MillerJaeb Center for Health Research, Tampa, Florida.
Brandon NathanUniversity of Minnesota, Minneapolis, Minnesota.
Laura PyleDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Darcy KahnDivision of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Michael TanseyStead Family Department of Pediatrics, Endocrinology and Diabetes, University of Iowa, Iowa City, Iowa.
Eileen TichyYale School of Medicine University, New Haven, Connecticut.
Eva TsalikianStead Family Department of Pediatrics, Endocrinology and Diabetes, University of Iowa, Iowa City, Iowa.
Ingrid LibmanChildren's Hospital of Pittsburgh at University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Kristen J NadeauDivision of Pediatric Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
University of Colorado Anschutz Medical Campus · USUniversity of Iowa · USYale University · USChildren's Hospital of Pittsburgh · USColorado School of Public Health · USIndiana University School of MedicineJaeb Center for Health Research · USNemours Children's Clinic · USUniversity of Minnesota System · US

Funding

Yale Diabetes Research CenterP30DK045735 · YALE UNIVERSITY · 1993 to 2025
$10.2M
University of Pittsburgh Clinical and Translational Science InstituteUL1TR001857 · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2025 to 2025
$10.1M
Yale Clinical and Translational Science AwardUL1TR001863 · YALE UNIVERSITY · 2025 to 2025
$9.9M
PILOT STUDY--SUBSTRATE METABOLISM IN EXTREMELY LOW BIRTH WEIGHT INFANTSP30DK048520 · UNIVERSITY OF COLORADO DENVER · 1995 to 2025
$7.7M
Translation CoreP30DK097512 · INDIANA UNIVERSITY INDIANAPOLIS · 2025 to 2025
$1.7M
The Next Generation of Innovative Cardiovascular Clinical/Translational ResearchersK24HL145076 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI KRISTEN Jane NADEAU · 2022 to 2023
$230k
NCATS NIH HHS UL1 TR001857NCATS NIH HHS UL1 TR001863NCATS NIH HHS UL1 TR002535NCATS NIH HHS UL1 TR002537NHLBI NIH HHS K24 HL145076NIDDK NIH HHS P30 DK045735NIDDK NIH HHS P30 DK048520NIDDK NIH HHS P30 DK097512
6 · The paper itself

Abstract

contextType 1 diabetes in adolescence is characterized by insulin deficiency and insulin resistance (IR), both thought to increase cardiovascular disease risk. We previously demonstrated that adolescents with type 1 diabetes have adipose, hepatic, and muscle IR, and that metformin lowers daily insulin dose, suggesting improved IR. However, whether metformin improves IR in muscle, hepatic, or adipose tissues in type 1 diabetes was unknown.

objectiveMeasure peripheral, hepatic, and adipose insulin sensitivity before and after metformin or placebo therapy in youth with obesity with type 1 diabetes.

designDouble-blind, placebo-controlled clinical trial.

settingMulti-center at eight sites of the T1D Exchange Clinic Network.

participantsA subset of 12- to 19-year-olds with type 1 diabetes (inclusion criteria: body mass index ≥85th percentile, HbA1c 7.5% to 9.9%, insulin dosing ≥0.8 U/kg/d) from a larger trial (NCT02045290) were enrolled.

interventionParticipants were randomized to 3 months of metformin (N = 19) or placebo (N = 18) and underwent a three-phase hyperinsulinemic euglycemic clamp with glucose and glycerol isotope tracers to assess tissue-specific IR before and after treatment.

main outcome measuresPeripheral insulin sensitivity, endogenous glucose release, rate of lipolysis.

resultsBetween-group differences in change in insulin sensitivity favored metformin regarding whole-body IR [change in glucose infusion rate 1.3 (0.1, 2.4) mg/kg/min, P = 0.03] and peripheral IR [change in metabolic clearance rate 0.923 (-0.002, 1.867) dL/kg/min, P = 0.05]. Metformin did not impact insulin suppression of endogenous glucose release (P = 0.12). Adipose IR was not assessable with traditional methods in this highly IR population.

conclusionsMetformin appears to improve whole-body and peripheral IR in youth who are overweight/obese with type 1 diabetes.

Indexed as

Insulin ResistanceAdipose TissueAdolescentAdultBlood GlucoseChildDiabetes Mellitus, Type 1Double-Blind MethodFemaleHumansHypoglycemic AgentsLiverMaleMetforminYoung AdultBlood GlucoseHypoglycemic AgentsMetformin

Identifiers

PMID30938764
PMCPMC6584133
OpenAlexW2932901353

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.