Evidence map›Paper›PMID 34765951›Full record

ArticleEClinicalMedicine2021

Net effects of sodium-glucose co-transporter-2 inhibition in different patient groups: a meta-analysis of large placebo-controlled randomized trials.

Natalie Staplin, Alistair J Roddick, Jonathan Emberson, Christina Reith, Alex Riding, Alexa Wonnacott, Apexa Kuverji, Sunil Bhandari, Colin Baigent, Richard Haynes and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EClinicalMedicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 5 pooled it
7.5field-weighted citation impact, top 2% 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

35 citing papers in PubMed, 5 syntheses or guidelines pooled it, 71 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Guideline
  4. Pooled it
  5. Pooled it
  6. Empagliflozin in Patients with Chronic Kidney Disease.The New England journal of medicine · 2023 · on this map
    Trial
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Hyperkalemia and maintenance of renin-angiotensin system inhibitor therapy after initiating SGLT-2 or DPP-4 inhibitors.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025
    Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article
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

11 authors at 6 institutions in 1 country.

Natalie StaplinMedical Research Council Population Health Research Unit at the University of Oxford, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health (NDPH), University of Oxford, Oxford, UK.
Alistair J RoddickMedical Research Council Population Health Research Unit at the University of Oxford, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health (NDPH), University of Oxford, Oxford, UK.
Jonathan EmbersonMedical Research Council Population Health Research Unit at the University of Oxford, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health (NDPH), University of Oxford, Oxford, UK.
Christina ReithMedical Research Council Population Health Research Unit at the University of Oxford, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health (NDPH), University of Oxford, Oxford, UK.
Alex RidingCambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Alexa WonnacottWales Kidney Research Unit, Cardiff University, Cardiff, UK.
Apexa KuverjiJohn Walls Renal Unit, Leicester General Hospital, University Hospitals of Leicester, Leicester, UK.
Sunil BhandariHull University Teaching Hospitals NHS Trust and Hull York Medical School, Hull, UK.
Colin BaigentMedical Research Council Population Health Research Unit at the University of Oxford, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health (NDPH), University of Oxford, Oxford, UK.
Richard HaynesMedical Research Council Population Health Research Unit at the University of Oxford, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health (NDPH), University of Oxford, Oxford, UK.
William G HerringtonMedical Research Council Population Health Research Unit at the University of Oxford, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health (NDPH), University of Oxford, Oxford, UK.
University of Oxford · GBChurchill Hospital · GBCambridge University Hospitals NHS Foundation Trust · GBCardiff University · GBHull York Medical School · GBLeicester General Hospital · GB

Funding

Cancer Research UK 16896Medical Research Council MC_U137686849Medical Research Council MC_U137686861Medical Research Council MC_UU_00017/3Medical Research Council MC_UU_00017/4Medical Research Council MC_UU_12026/6Medical Research Council MR/R007764/1
6 · The paper itself

Abstract

backgroundThe net absolute effects of sodium-glucose co-transporter-2 (SGLT-2) inhibitors across different patient groups have not been quantified.

methodsWe performed a meta-analysis of published large (>500 participants/arm) placebo-controlled SGLT-2 inhibitor trials after systematically searching MEDLINE and Embase databases from inception to 28th August 2021 (PROSPERO 2021 CRD42021240468).

findingsFour heart failure trials (n=15,684 participants), four trials in type 2 diabetes mellitus at high atherosclerotic cardiovascular risk (n=42,568), and three trials in chronic kidney disease (n=19,289) were included. Relative risks (RRs) for all cardiovascular, renal and safety outcomes were broadly similar across these three patient groups, and between people with or without diabetes. Overall, compared to placebo, allocation to SGLT-2 inhibition reduced risk of hospitalization for heart failure or cardiovascular death by 23% (RR=0.77, 95%CI 0.73-0.80; n=6658), cardiovascular death by 14% (0.86, 0.81-0.92; n=3962), major adverse cardiovascular events by 11% (0.89, 0.84-0.94; n=5703), kidney disease progression by 36% (0.64, 0.59-0.70; n=2275), acute kidney injury by 30% (0.70, 0.62-0.79; n=1013 events) and severe hypoglycaemia by 13% (0.87, 0.79-0.97; n=1484). There was no effect of SGLT-2 inhibition on risk of non-cardiovascular death (0.93, 0.86-1.01; n=2226), but a net 12% reduction in all-cause mortality remained evident (0.88, 0.84-0.93; n=6188). However, the risk of ketoacidosis was 2-times higher among those allocated SGLT-2 inhibitors compared to placebo (2.03, 1.41-2.93; n=159; absolute excess in people with diabetes ∼0.3/1000 patient years). A small increased risk of urinary tract infection was evident (1.07, 1.02-1.13; n=5384) alongside a known increased risk of mycotic genital infections. Overall, risk of lower limb amputations was increased by 16% (1.16, 1.02-1.31; n=1074), but this risk was largely driven by a single outlying trial (CANVAS). INTERPRETATIONS: The relative effects of SGLT-2 inhibition on key safety and efficacy outcomes are consistent across the different studied groups of patient. Consequently, absolute benefits and harms are determined by the absolute baseline risk of particular outcomes, with absolute benefits on mortality and on non-fatal serious cardiac/renal outcomes substantially exceeding the risks of amputation and ketoacidosis in the main patient groups studied to date.

fundingMRC-UK & KRUK.

Indexed as

CKDHeart failureRandomized trialsSafetySodium-glucose co-transporter 2 inhibitors

Identifiers

PMID34765951
PMCPMC8571171
OpenAlexW3208816106

What OpenQuestion 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 OpenQuestion graph.