Trial reportDiabetes care2025

Short-term Metformin Protects Against Glucocorticoid-Induced Toxicity in Healthy Individuals: A Randomized, Double-Blind, Placebo-Controlled Trial.

Susanne Thierry, Caspar Joyce Peterson, Stéphanie Pfammatter, Patricia Arroyo Tardio, Christian Meier, Tarik Delko, Vasco Iten, Christine S Zuern, Michael Kühne, Michael Epstein and 6 more

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Diabetes care, 2025. The graph read 1 number from its abstract, feeding 1 cell of the map: it . Cited by 5 papers, 2 of them syntheses that pooled it.

1number the graph read from it
1cell of the map it votes in
5citing papers in PubMed, 2 pooled it
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 comparatorfavours the treatment →
-7.240 · no effect
Glycemic controlfavours the comparator · head-to-head · t2dfeeds one cell of the map
Δ -4.94-7.24 to -2.65P < 0.001
RESULTS: Metformin improved insulin sensitivity as assessed by the Matsuda index (n = 17; mean change -2.73 ± 3.55 SD for placebo, 2.21 ± 3.95 for metformin; mean difference of change -4.94 [95% CI, -7.24, -2.65]; P < 0.001).

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

No readable resultOpen on the map →What to test next →

40 readable studies in this cell: 41 favour the treatment, 13 find no difference, 7 favour the comparator.

Belief with this paper
0.84replicated · 32 families support, 6 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
0 · no effect
This paper · 2025
Δ -4.94-7.24 to -2.65
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

5 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Review
  5. Review
6 · The record

Corrections and comments

7 · Who and what money

Authors and funding

16 authors.

Susanne ThierryDivision of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland.
Caspar Joyce PetersonClarunis, Department of Visceral Surgery, University Center for Gastrointestinal and Liver Diseases, St. Claraspital and University Hospital Basel, Basel, Switzerland.
Stéphanie PfammatterDivision of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland.
Patricia Arroyo TardioDivision of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland.
Christian MeierDivision of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland.
Tarik DelkoClarunis, Department of Visceral Surgery, University Center for Gastrointestinal and Liver Diseases, St. Claraspital and University Hospital Basel, Basel, Switzerland.
Vasco ItenCardiovascular Research Institute Basel, University Hospital Basel, Basel, Switzerland.
Christine S ZuernCardiovascular Research Institute Basel, University Hospital Basel, Basel, Switzerland.
Michael KühneCardiovascular Research Institute Basel, University Hospital Basel, Basel, Switzerland.
Michael EpsteinStatistical Consulting, Letchworth, U.K.
Alaa OthmanInstitute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
Nicola ZamboniInstitute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
Isabel ReinischLaboratory of Translational Nutrition Biology, Institute of Food, Nutrition and Health, ETH Zurich, Schwerzenbach, Switzerland.
Adhideb GhoshLaboratory of Translational Nutrition Biology, Institute of Food, Nutrition and Health, ETH Zurich, Schwerzenbach, Switzerland.
Christian WolfrumLaboratory of Translational Nutrition Biology, Institute of Food, Nutrition and Health, ETH Zurich, Schwerzenbach, Switzerland.
Eleonora SeeligDivision of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland.ORCID 0000-0002-7092-1986

Funding

ETHNovartis FoundationSwiss Diabetes FoundationSwiss Federal InstitutesSwissLife Jubilee FoundationSwiss National Science Foundation 193516
8 · The paper itself

Abstract

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

objectiveGlucocorticoids (GCs) are potent anti-inflammatory drugs, but strategies to prevent side effects are lacking. We investigated whether metformin could prevent GC-related toxicity and explored the underlying mechanisms. RESEARCH DESIGN AND

methodsThis single-center, randomized, placebo-controlled, double-blind, crossover trial compared metformin with placebo during high-dose GC treatment in 18 lean, healthy, male study participants. The trial was conducted at the University Hospital Basel, Basel, Switzerland. Participants received prednisone 30 mg/day in combination with metformin or placebo for two 7-day periods (1:1 randomization). The primary outcome, change in insulin sensitivity, was assessed using a two-sided paired t test. Before and after each study period, we conducted a mixed-meal tolerance test, blood metabolomics, and RNA sequencing of subcutaneous adipose tissue biopsy specimens.

resultsMetformin improved insulin sensitivity as assessed by the Matsuda index (n = 17; mean change -2.73 ± 3.55 SD for placebo, 2.21 ± 3.95 for metformin; mean difference of change -4.94 [95% CI, -7.24, -2.65]; P < 0.001). Metabolomic and transcriptomic analyses revealed that metformin altered fatty acid flux in the blood and downregulated genes involved in fatty acid synthesis in adipose tissue. Metformin reduced markers of protein breakdown and bone resorption. Furthermore, metformin downregulated genes responsible for AMPK inhibition and affected glucagon-like peptide 1 and bile acid metabolism.

conclusionsMetformin prevents GC-induced insulin resistance and reduces markers of dyslipidemia, myopathy, and, possibly, bone resorption through AMPK-dependent and -independent pathways.

Indexed as

GlucocorticoidsHypoglycemic AgentsMetforminAdultCross-Over StudiesDouble-Blind MethodHumansInsulin ResistanceMaleMiddle AgedGlucocorticoidsHypoglycemic AgentsMetformin

Identifiers

PMID39899467
PMCPMC12034906

What Socratic holds

Texttitle and abstract
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.