Trial reportNature communications2025

Effect of metformin on insulin resistance in adults with type 1 diabetes: a 26-week randomized double-blind clinical trial.

Jennifer R Snaith, Nick Olsen, Jennifer Evans, Greg M Kowalski, Clinton R Bruce, Dorit Samocha-Bonet, Samuel N Breit, Deborah J Holmes-Walker, Jerry R Greenfield

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Nature communications, 2025. The graph read 1 number from its abstract, feeding 1 cell of the map: it finds no clear difference in 1. Cited by 3 papers.

1number the graph read from it
1cell of the map it votes in
3citing papers in PubMed
field-weighted citation impact
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.

← favours the treatmentfavours the comparator →
-0.400.800 · no effect
Change in endogenous glucose production (EGP) during the low-dose phase of the clampmetformin 1500 mg vs placebono clear difference · t1d, t2dfeeds one cell of the map
Δ 0.20-0.40 to 0.800.53
At 26 weeks, there was no difference in change in EGP between metformin and placebo groups (mean difference 0.2 µmol/kg fat-free mass [FFM]/min [95%CI, -0.4 to 0.8 µmol/kgFFM/min]; p = 0.53).

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

Metformin×glycemic control

InconclusiveOpen on the map →What to test next →

40 readable studies in this cell: 41 favour the treatment, 12 find no difference, 8 favour the comparator.

Belief with this paper
0.84replicated · 32 families support, 6 contradict · against placebo
Without it
0.84This paper does not move the number.
← favours the treatmentfavours the comparator →
0 · no effect
This paper · 2025
Δ 0.20-0.40 to 0.80
NCT017190031,413 enrolled · 2012
Adjusted mean -0.72-0.95 to -0.48
NCT018093271,186 enrolled · 2013
Δ -0.40-0.59 to -0.21
NCT022730501,136 enrolled · 2014
Δ -0.89-1.08 to -0.69
NCT008598981,093 enrolled · 2009
Δ -0.53-0.74 to -0.32
Δ -0.85-43.8 to 26.7
NCT00643851994 enrolled · 2008
Δ -0.86-1.11 to -0.62
NCT01708902876 enrolled · 2012
Δ -1.00-1.23 to -0.78
NCT00676338820 enrolled · 2008
Δ -0.05-0.26 to 0.17
NCT01126580807 enrolled · 2010
Δ -0.22-0.36 to -0.08
NCT01023581784 enrolled · 2009
Δ -0.67-0.96 to -0.37
NCT01076088744 enrolled · 2010
Δ -0.84-1.15 to -0.52
NCT00386100688 enrolled · 2006
Δ -0.49-0.67 to -0.30
4 · 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

5 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Metabolic dysfunction and the use of adjunct medications in type 1 diabetes.Current opinion in endocrinology, diabetes, and obesity · 2026
    Review
  2. Article
  3. Review
6 · The record

Corrections and comments

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

7 · Who and what money

Authors and funding

9 authors.

Jennifer R SnaithClinical Diabetes, Appetite and Metabolism Laboratory, Garvan Institute of Medical Research, Sydney, NSW, Australia. j.snaith@garvan.org.au.ORCID http://orcid.org/0000-0001-8559-8387
Nick OlsenStats Central, Mark Wainwright Analytical Centre, University of New South Wales, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0001-7990-3197
Jennifer EvansClinical Diabetes, Appetite and Metabolism Laboratory, Garvan Institute of Medical Research, Sydney, NSW, Australia.
Greg M KowalskiInstitute for Physical Activity and Nutrition, Metabolic Research Unit, School of Medicine, Deakin University, Geelong, VIC, Australia.ORCID http://orcid.org/0000-0002-1599-017X
Clinton R BruceInstitute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, VIC, Australia.ORCID http://orcid.org/0000-0002-0515-3343
Dorit Samocha-BonetClinical Diabetes, Appetite and Metabolism Laboratory, Garvan Institute of Medical Research, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0001-9422-7852
Samuel N BreitSt Vincent's Healthcare Campus, Faculty of Medicine and Health, University of New South Wales Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0002-9021-9879
Deborah J Holmes-WalkerDepartment of Diabetes and Endocrinology, Westmead Hospital, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0002-3640-1370
Jerry R GreenfieldClinical Diabetes, Appetite and Metabolism Laboratory, Garvan Institute of Medical Research, Sydney, NSW, Australia.

Funding

No grant is acknowledged in the PubMed record.

8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

Insulin resistance is an underrecognized cardiovascular risk factor in type 1 diabetes. The effect of metformin on insulin resistance in adults with type 1 diabetes is unknown. Forty adults with type 1 diabetes, and twenty adults without diabetes were studied in a baseline only cross-sectional study assessing insulin resistance using the two-step hyperinsulinemic-euglycemic clamp. Participants with type 1 diabetes exhibited hepatic (EGP 64% higher), muscle (glucose infusion rate [GIR] 29% lower) and adipose (higher non-esterified fatty acids [NEFA]) insulin resistance. We then conducted a parallel group randomized, placebo-controlled trial to assess the efficacy of metformin 1500 mg (n = 20) versus placebo (n = 20) in reducing insulin resistance in adults with type 1 diabetes over 26 weeks. The primary outcome was change in endogenous glucose production (EGP) during the low-dose phase of the clamp. Thirty seven of 40 adults with type 1 diabetes completed the study. At 26 weeks, there was no difference in change in EGP between metformin and placebo groups (mean difference 0.2 µmol/kg fat-free mass [FFM]/min [95%CI, -0.4 to 0.8 µmol/kgFFM/min]; p = 0.53). There was no increase in hypoglycemia or episodes of ketoacidosis in either group. These results do not support prescribing metformin to reduce hepatic insulin resistance in adults with type 1 diabetes. Australian New Zealand Clinical Trials Registry identifier, ACTRN12619001440112.

Indexed as

Diabetes Mellitus, Type 1Hypoglycemic AgentsInsulin ResistanceMetforminAdultBlood GlucoseCross-Sectional StudiesDouble-Blind MethodFatty Acids, NonesterifiedFemaleGlucoseGlucose Clamp TechniqueHumansLiverMaleMiddle AgedBlood GlucoseFatty Acids, NonesterifiedGlucoseHypoglycemic AgentsMetformin

Identifiers

PMID41285865
PMCPMC12644478

What Socratic holds

Texttitle and abstract
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.