Evidence map›Paper›PMID 34774144›Full record

ArticleLancet (London, England)2021

Blood pressure lowering and risk of new-onset type 2 diabetes: an individual participant data meta-analysis.

Milad Nazarzadeh, Zeinab Bidel, Dexter Canoy, Emma Copland, Malgorzata Wamil, Jeannette Majert, Karl Smith Byrne, Johan Sundström, Koon Teo, Barry R Davis and 7 more

Open access · hybridAbstract readNetwork Meta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Article in Lancet (London, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed, 4 pooled it
14.0field-weighted citation impact, top 1% 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.

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

3 · Its place in the literature

Who cites it

83 citing papers in PubMed, 4 syntheses or guidelines pooled it, 128 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Systematically exploring repurposing effects of antihypertensives.Pharmacoepidemiology and drug safety · 2022
    Pooled it
  4. Pooled it
  5. ENAC blockade reduces blood pressure and arterial stiffness in adults with obesity and insulin resistance.American journal of physiology. Heart and circulatory physiology · 2026
    Trial
  6. Trial
  7. Article
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  10. Evidence-based blood tests for monitoring adults with hypertension in primary care: rapid review, routine data analyses, and consensus study.The British journal of general practice : the journal of the Royal College of General Practitioners · 2026
    Review
  11. Article
  12. Review
  13. Cardiovascular Pharmacotherapy and Glucose Metabolism: The Good, the Bad and the Unsightly.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2026
    Review
  14. Article
  15. Article
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23 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 9 institutions in 6 countries.

Milad NazarzadehDeep Medicine, Oxford Martin School, University of Oxford, Oxford, UK; Nuffield Department of Women's and Reproductive Health, Medical Science Division, University of Oxford, Oxford, UK.
Zeinab BidelDeep Medicine, Oxford Martin School, University of Oxford, Oxford, UK; Nuffield Department of Women's and Reproductive Health, Medical Science Division, University of Oxford, Oxford, UK.
Dexter CanoyDeep Medicine, Oxford Martin School, University of Oxford, Oxford, UK; Nuffield Department of Women's and Reproductive Health, Medical Science Division, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Emma CoplandDeep Medicine, Oxford Martin School, University of Oxford, Oxford, UK; Nuffield Department of Women's and Reproductive Health, Medical Science Division, University of Oxford, Oxford, UK.
Malgorzata WamilDeep Medicine, Oxford Martin School, University of Oxford, Oxford, UK.
Jeannette MajertDeep Medicine, Oxford Martin School, University of Oxford, Oxford, UK; Nuffield Department of Women's and Reproductive Health, Medical Science Division, University of Oxford, Oxford, UK.
Karl Smith ByrneInternational Agency for Research on Cancer/WHO, Genomic Epidemiology Branch, Lyon, France.
Johan SundströmClinical Epidemiology Unit, Department of Medical Sciences, Uppsala University, Uppsala, Sweden; The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.
Koon TeoPopulation Health Research Institute, McMaster University, Hamilton, ON, Canada.
Barry R DavisThe University of Texas School of Public Health, Houston, TX, USA.
John ChalmersThe George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.
Carl J PepineDepartment of Medicine, University of Florida, Gainesville, FL, USA.
Abbas DehghanDepartment of Biostatistics and Epidemiology, School of Public Health, Imperial College London, London, UK.
Derrick A BennettClinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
George Davey SmithMRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Kazem RahimiDeep Medicine, Oxford Martin School, University of Oxford, Oxford, UK; Nuffield Department of Women's and Reproductive Health, Medical Science Division, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK. Electronic address: kazem.rahimi@wrh.ox.ac.uk.
Blood Pressure Lowering Treatment Trialists’ Collaboration
University of Oxford · GBOxford BioMedica (United Kingdom) · GBUNSW Sydney · AUCentre International de Recherche sur le Cancer · FRImperial College London · GBMRC Epidemiology Unit · GBPopulation Health Research Institute · CAThe University of Texas Health Science Center at Houston · USUniversity of Florida · US

Funding

British Heart Foundation FS/19/36/34346British Heart Foundation PG/18/65/33872Medical Research Council MC_UU_00011/1World Health Organization 001
6 · The paper itself

Abstract

backgroundBlood pressure lowering is an established strategy for preventing microvascular and macrovascular complications of diabetes, but its role in the prevention of diabetes itself is unclear. We aimed to examine this question using individual participant data from major randomised controlled trials.

methodsWe performed a one-stage individual participant data meta-analysis, in which data were pooled to investigate the effect of blood pressure lowering per se on the risk of new-onset type 2 diabetes. An individual participant data network meta-analysis was used to investigate the differential effects of five major classes of antihypertensive drugs on the risk of new-onset type 2 diabetes. Overall, data from 22 studies conducted between 1973 and 2008, were obtained by the Blood Pressure Lowering Treatment Trialists' Collaboration (Oxford University, Oxford, UK). We included all primary and secondary prevention trials that used a specific class or classes of antihypertensive drugs versus placebo or other classes of blood pressure lowering medications that had at least 1000 persons-years of follow-up in each randomly allocated arm. Participants with a known diagnosis of diabetes at baseline and trials conducted in patients with prevalent diabetes were excluded. For the one-stage individual participant data meta-analysis we used stratified Cox proportional hazards model and for the individual participant data network meta-analysis we used logistic regression models to calculate the relative risk (RR) for drug class comparisons.

findings145 939 participants (88 500 [60·6%] men and 57 429 [39·4%] women) from 19 randomised controlled trials were included in the one-stage individual participant data meta-analysis. 22 trials were included in the individual participant data network meta-analysis. After a median follow-up of 4·5 years (IQR 2·0), 9883 participants were diagnosed with new-onset type 2 diabetes. Systolic blood pressure reduction by 5 mm Hg reduced the risk of type 2 diabetes across all trials by 11% (hazard ratio 0·89 [95% CI 0·84-0·95]). Investigation of the effects of five major classes of antihypertensive drugs showed that in comparison to placebo, angiotensin-converting enzyme inhibitors (RR 0·84 [95% 0·76-0·93]) and angiotensin II receptor blockers (RR 0·84 [0·76-0·92]) reduced the risk of new-onset type 2 diabetes; however, the use of β blockers (RR 1·48 [1·27-1·72]) and thiazide diuretics (RR 1·20 [1·07-1·35]) increased this risk, and no material effect was found for calcium channel blockers (RR 1·02 [0·92-1·13]).

interpretationBlood pressure lowering is an effective strategy for the prevention of new-onset type 2 diabetes. Established pharmacological interventions, however, have qualitatively and quantitively different effects on diabetes, likely due to their differing off-target effects, with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers having the most favourable outcomes. This evidence supports the indication for selected classes of antihypertensive drugs for the prevention of diabetes, which could further refine the selection of drug choice according to an individual's clinical risk of diabetes.

fundingBritish Heart Foundation, National Institute for Health Research, and Oxford Martin School.

Indexed as

Adrenergic beta-AntagonistsAgedAngiotensin-Converting Enzyme InhibitorsAngiotensin Receptor AntagonistsAntihypertensive AgentsBlood PressureCalcium Channel BlockersDiabetes Mellitus, Type 2FemaleHumansHypertensionMaleMiddle AgedSodium Chloride Symporter InhibitorsAdrenergic beta-AntagonistsAngiotensin-Converting Enzyme InhibitorsAngiotensin Receptor AntagonistsAntihypertensive AgentsCalcium Channel BlockersSodium Chloride Symporter Inhibitors

Identifiers

PMID34774144
PMCPMC8585669
OpenAlexW3211912548

What Socratic holds

Textmetadata
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.