Evidence map›Paper›PMID 42875657›Full record

ArticleDrugs2026

Metformin Lowers Fasting Hyperglycemia by Increasing Glucose Clearance in People with Moderately Controlled Type 2 Diabetes.

Sabine Kahl, Traci E LaMoia, Marc Jonuscheit, Geronimo Heilmann, Sophie Rohrer, Pavel Bobrov, Bedair Dewidar, Kalliopi Pafili, Theresia Sarabhai, Vera Schrauwen-Hinderling and 3 more

Registry-linked trialAbstract read
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In one paragraph

Article in Drugs, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT04088851. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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.

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.

NCT04088851 naactive not recruiting

"Non-invasive Measurement of Hepatic Substrate Flux Rates in People with Diabetes Mellitus Type 2"

Ran2019Enrolled23Registered outcomes6Posted comparisons0ConditionsType 2 DiabetesArmsOff Metformin, On Metformin
Open the trial in the graph
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

13 authors.

Sabine KahlInstitute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany.
Traci E LaMoiaDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
Marc JonuscheitInstitute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany.
Geronimo HeilmannInstitute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany.
Sophie RohrerInstitute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany.
Pavel BobrovGerman Center for Diabetes Research (DZD e.V.), Partner Düsseldorf, Neuherberg, Germany.
Bedair DewidarInstitute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany.
Kalliopi PafiliInstitute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany.
Theresia SarabhaiInstitute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany.
Vera Schrauwen-HinderlingInstitute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany.
Gerald I ShulmanDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
Kitt Falk PetersenDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
Michael RodenInstitute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany. michael.roden@ddz.de.

Funding

European Community HORIZON-HLTH-2022-STAYHLTH-02-01: Panel ANovo Nordisk Fonden NNF25SA0106990United States National Institutes of Health P30DK45735United States National Institutes of Health R01DK135645United States National Institutes of Health UL1RR024139
6 · The paper itself

Abstract

BACKGROUND/

objectiveMetformin is the most frequently prescribed antidiabetic drug worldwide; however, the mechanism by which it lowers blood glucose remains incompletely understood. The objective of this study was to examine the effects of metformin on whole-body and specifically on hepatic glucose and energy metabolism in type 2 diabetes.

methodsThis open repeated-measures pilot study examined this question using Positional Isotopomer NMR Tracer Analysis (PINTA) to assess rates of endogenous glucose production (V

resultsM+ reduced fasting glycemia by 18%, which could mostly be attributed to a 24% increase in rates of whole-body glucose clearance. Surprisingly, these changes were accompanied by a 58% increase in V

conclusionMetformin treatment in male individuals of European ancestry with moderately controlled T2D decreases blood glucose concentrations by increasing rates of whole-body glucose clearance. Metformin further inhibits glycerol-derived gluconeogenesis, which is consistent with complex IV, not complex I, being the molecular target of metformin action.

trial registrationClinicalTrials.gov ( https://clinicaltrials.gov/ ): NCT04088851.

Identifiers

PMID42875657

What OpenQuestion holds

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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.