Evidence mapPaperPMID 8013758Full record

Trial reportDiabetes1994

Acute antihyperglycemic mechanisms of metformin in NIDDM. Evidence for suppression of lipid oxidation and hepatic glucose production.

G Perriello, P Misericordia, E Volpi, A Santucci, C Santucci, E Ferrannini, M M Ventura, F Santeusanio, P Brunetti, G B Bolli

2 registry-linked trialsAbstract readClinical TrialComparative StudyControlled Clinical Trial
PubMed Publisher
In one paragraph

Trial report in Diabetes, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 45 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 4 pooled it
4.4field-weighted citation impact, top 5% 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.

NCT01589445 phase4completedstarted 2008, after this paper: background citation

Modulation of Insulin Secretion and Insulin Sensitivity in Bangladeshi Type 2 Diabetic Subjects by an Insulin Sensitizer Pioglitazone and T2DM Association With PPARG Gene Polymorphism.

Ran2008Enrolled77Registered outcomes6Posted comparisons11ConditionsType 2 Diabetes MellitusArmsMetformin hydrochloride, pioglitazone hydrochloride
Open the trial in the graph
NCT04841668 completedstarted 2021, after this paper: background citation

Gut-Brain-axis: Targets for Improvement of Cognition in the Elderly

Ran2021Enrolled50Registered outcomes51Posted comparisons0ConditionsType 2 Diabetes MellitusArmsMetformin
Open the trial in the graph
3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 4 syntheses or guidelines pooled it, 217 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus.The Cochrane database of systematic reviews · 2010 · on this map
    Pooled it
  4. Pooled it
  5. Trial
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  9. Article
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  12. Metformin prevents airway hyperreactivity in rats with dietary obesity.American journal of physiology. Lung cellular and molecular physiology · 2021
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  14. Review
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  16. Review
  17. Article
  18. Article
  19. A role forJournal of molecular endocrinology · 2017
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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

10 authors at 2 institutions in 1 country.

G PerrielloDipartimento di Medicina Interna e Scienze Endocrine e Metaboliche, University of Perugia, Italy.
P Misericordia
E Volpi
A Santucci
C Santucci
E Ferrannini
M M Ventura
F Santeusanio
P Brunetti
G B Bolli
University of Perugia · ITIstituto di Fisiologia Clinica · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

To establish the antihyperglycemic mechanisms of metformin in non-insulin-dependent diabetes mellitus (NIDDM) independently of the long-term, aspecific effects of removal of glucotoxicity, 21 NIDDM subjects (14 obese, 7 nonobese) were studied on two separate occasions, with an isoglycemic (plasma glucose approximately 9 mM) hyperinsulinemic (two-step insulin infusion, 2 h each, at the rate of 4 and 40 mU.m-2.min-1) clamp combined with [3-3H]glucose infusion and indirect calorimetry, after administration of either metformin (500 mg per os, at -5 and -1 h before the clamp) or placebo. Compared with placebo, hepatic glucose production (HGP) decreased approximately 30% more after metformin (from 469 +/- 50 to 330 +/- 54 mumol/min), but glucose uptake did not increase. Metformin suppressed free fatty acids (FFAs) by approximately 17% (from 0.42 +/- 0.04 to 0.35 +/- 0.04 mM) and lipid oxidation by approximately 25% (from 4.5 +/- 0.4 to 3.4 +/- 0.4 mumol.kg-1.min-1) and increased glucose oxidation by approximately 16% (from 16.2 +/- 1.4 to 19.3 +/- 1.3 mumol.kg-1.min-1) compared with placebo (P < 0.05), but did not affect nonoxidative glucose metabolism, protein oxidation, or total energy expenditure. Suppression of FFA and lipid oxidation after metformin correlated with suppression of HGP (r = 0.70 and r = 0.51, P < 0.001). The effects of metformin in obese and nonobese subjects were no different. We conclude that the specific, antihyperglycemic effects of metformin in the clinical condition of hyperglycemia in NIDDM are primarily due to suppression of HGP, not stimulation of glucose uptake, and are mediated, at least in part, by suppression of FFA and lipid oxidation.

Indexed as

ObesityAdultBlood GlucoseBody Mass IndexDiabetes MellitusDiabetes Mellitus, Type 2Fatty Acids, NonesterifiedFemaleGluconeogenesisGlucoseGlucose Clamp TechniqueGlycated HemoglobinHumansInsulinLiverMaleBlood GlucoseFatty Acids, NonesterifiedGlucoseGlycated HemoglobinInsulinMetformin

Identifiers

PMID8013758
OpenAlexW1966224374

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.