Trial reportCardiovascular diabetology2020

Metformin may adversely affect orthostatic blood pressure recovery in patients with type 2 diabetes: substudy from the placebo-controlled Copenhagen Insulin and Metformin Therapy (CIMT) trial.

Christian Stevns Hansen, Louise Lundby-Christiansen, Lise Tarnow, Christian Gluud, Christoffer Hedetoft, Birger Thorsteinsson, Bianca Hemmingsen, Niels Wiinberg, Simone B Sneppen, Søren S Lund and 6 more

Open access · goldFull text readRandomized Controlled Trial
In one paragraph

Trial report in Cardiovascular diabetology, 2020. The graph read 2 numbers from its abstract, feeding 1 cell of the map: it favours the comparator in 1. Cited by 7 papers, 2 of them syntheses that pooled it.

2numbers the graph read from it
1cell of the map it votes in
7citing papers in PubMed, 2 pooled it
2.5field-weighted citation impact, top 10% 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.

← favours the treatmentfavours the comparator →
6.200 · no effect
Blood pressurefavours the comparator · against placebo · hypertension, t2dfeeds one cell of the map
increase 3.400.60 to 6.20p = 0.02
RESULTS: After 18 months early drop in OBP (30 s after standing) was increased in the metformin group compared to placebo: systolic blood pressure drop increased by 3.4 mmHg (95% CI 0.6; 6.2, p = 0.02) and diastolic blood pressure drop increased by 1.3 mmHg (95% CI 0.3; 2.6, p = 0.045) compared to placebo.
Blood pressurefavours the comparator · against placebo · hypertension, t2dfeeds one cell of the map
increase 1.300.30 to 2.60p = 0.045
RESULTS: After 18 months early drop in OBP (30 s after standing) was increased in the metformin group compared to placebo: systolic blood pressure drop increased by 3.4 mmHg (95% CI 0.6; 6.2, p = 0.02) and diastolic blood pressure drop increased by 1.3 mmHg (95% CI 0.3; 2.6, p = 0.045) compared to placebo.

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×blood pressure

ContradictsOpen on the map →What to test next →

6 readable studies in this cell: 2 favour the treatment, 3 find no difference, 1 favour the comparator.

Belief with this paper
0.40contested · 1 family supports, 1 contradict · against placebo
Without it
0.50This paper moves it by −0.10. It would be one trial.
← favours the treatmentfavours the comparator →
0 · no effect
This paper · 2020
increase 3.400.60 to 6.20
NCT00676338820 enrolled · 2008
Δ 0.36-1.02 to 1.73
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

7 citing papers in PubMed, 2 syntheses or guidelines pooled it, 17 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Review
  5. Article
  6. Review
  7. Single Nucleotide Polymorphism in the 3' Untranslated Region ofTherapeutics and clinical risk management · 2022
    Article
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

16 authors at 8 institutions in 1 country.

Christian Stevns HansenSteno Diabetes Center Copenhagen, A/S, Niels Steensens Vej 2-4, 2820, Gentofte, Denmark. chan0583@regionh.dk.ORCID 0000-0002-5782-3476
Louise Lundby-ChristiansenSteno Diabetes Center Copenhagen, A/S, Niels Steensens Vej 2-4, 2820, Gentofte, Denmark.
Lise TarnowDepartment of Clinical Research, Nordsjaellands Hospital, Hillerød, Denmark.
Christian GluudCopenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Christoffer HedetoftDepartment of Medicine, University Hospital Køge, Køge, Denmark.
Birger ThorsteinssonDepartment of Cardiology, Nephrology and Endocrinology, Nordsjællands University Hospital - Hillerød, Hillerød, Denmark.
Bianca HemmingsenDepartment of Cardiology, Nephrology and Endocrinology, Nordsjællands University Hospital - Hillerød, Hillerød, Denmark.
Niels WiinbergDepartment of Clinical Physiology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
Simone B SneppenDepartment of Medicine, Gentofte, Copenhagen University Hospital, Hellerup, Denmark.
Søren S LundSteno Diabetes Center Copenhagen, A/S, Niels Steensens Vej 2-4, 2820, Gentofte, Denmark.
Thure KrarupDepartment of Endocrinology, Bispebjerg, Copenhagen University Hospital, Copenhagen, Denmark.
Sten MadsbadDepartment of Endocrinology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark.
Thomas AlmdalDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Bendix CarstensenSteno Diabetes Center Copenhagen, A/S, Niels Steensens Vej 2-4, 2820, Gentofte, Denmark.
Marit E JørgensenSteno Diabetes Center Copenhagen, A/S, Niels Steensens Vej 2-4, 2820, Gentofte, Denmark.
CIMT study group
University of Copenhagen · DKSteno Diabetes Centers · DKAarhus University · DKCopenhagen University Hospital · DKNordsjællands Hospital · DKBispebjerg Hospital · DKGentofte Hospital · DKZealand University Hospital Køge · DK

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.

backgroundMetformin has been shown to have both neuroprotective and neurodegenerative effects. The aim of this study was to investigate the effect of metformin in combination with insulin on cardiovascular autonomic neuropathy (CAN) and distal peripheral neuropathy (DPN) in individuals with type 2 diabetes (T2DM).

methodsThe study is a sub-study of the CIMT trial, a randomized placebo-controlled trial with a 2 × 3 factorial design, where 412 patients with T2DM were randomized to 18 months of metformin or placebo in addition to open-labelled insulin. Outcomes were measures of CAN: Changes in heart rate response to deep breathing (beat-to-beat), orthostatic blood pressure (OBP) and heart rate and vibration detection threshold (VDT) as a marker DPN. Serum levels of vitamin B12 and methyl malonic acid (MMA) were analysed.

resultsAfter 18 months early drop in OBP (30 s after standing) was increased in the metformin group compared to placebo: systolic blood pressure drop increased by 3.4 mmHg (95% CI 0.6; 6.2, p = 0.02) and diastolic blood pressure drop increased by 1.3 mmHg (95% CI 0.3; 2.6, p = 0.045) compared to placebo. Beat-to-beat variation decreased in the metformin group by 1.1 beats per minute (95% CI - 2.4; 0.2, p = 0.10). Metformin treatment did not affect VDT group difference - 0.33 V (95% CI - 1.99; 1.33, p = 0.39) or other outcomes. Changes in B12, MMA and HbA

conclusionsEighteen months of metformin treatment in combination with insulin compared with insulin alone increased early drop in OBP indicating an adverse effect of metformin on CAN independent of vitamin B12, MMA HbA

Indexed as

Standing PositionAgedAutonomic Nervous System DiseasesBlood PressureDiabetes Mellitus, Type 2Diabetic NeuropathiesFemaleGlycated HemoglobinHumansHypoglycemic AgentsHypotension, OrthostaticInsulinMaleMetforminMiddle AgedPeripheral Nervous System DiseasesGlycated Hemoglobinhemoglobin A1c protein, humanHypoglycemic AgentsInsulinMetforminVitamin B 12Autonomic neuropathyCardiovascular autonomic neuropathyComplicationsMetforminOrthostatic blood pressure recoveryOrthostatic hypotensionPeripheral neuropathyType 2 diabetes

Identifiers

PMID32979921
PMCPMC7520024
OpenAlexW3089051137

What Socratic holds

Textfull text, public
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.