Evidence map›Paper›PMID 41299446›Full record

ArticleBMC medicine2025

Assessing the representativeness of trials of Sodium-glucose Cotransporter-2 inhibitors in type 2 diabetes: a comparison of individual-level trial data and people newly prescribed treatment in a Welsh routine care database.

Peter Hanlon, Heather Wightman, Michael Sullivan, Jennifer S Lees, Elaine W Butterly, Lili Wei, Ryan McChrystal, Eva Whalley, Saleh Ali Almazam, Khalid Alsallumi and 6 more

Abstract readComparative Study
In one paragraph

Article in BMC medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. 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.

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

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

16 authors.

Peter HanlonUniversity of Glasgow School of Health and Wellbeing, Clarice Pears Building, 90 Byres Road, Glasgow, UK. Peter.hanlon@glasgow.ac.uk.
Heather WightmanUniversity of Glasgow School of Health and Wellbeing, Clarice Pears Building, 90 Byres Road, Glasgow, UK.
Michael SullivanUniversity of Glasgow School of Cardiovascular and Metabolic Health, Glasgow, UK.
Jennifer S LeesUniversity of Glasgow School of Cardiovascular and Metabolic Health, Glasgow, UK.
Elaine W ButterlyUniversity of Glasgow School of Health and Wellbeing, Clarice Pears Building, 90 Byres Road, Glasgow, UK.
Lili WeiUniversity of Glasgow School of Health and Wellbeing, Clarice Pears Building, 90 Byres Road, Glasgow, UK.
Ryan McChrystalUniversity of Glasgow School of Health and Wellbeing, Clarice Pears Building, 90 Byres Road, Glasgow, UK.
Eva WhalleyUniversity of Glasgow School of Health and Wellbeing, Clarice Pears Building, 90 Byres Road, Glasgow, UK.
Saleh Ali AlmazamUniversity of Glasgow School of Health and Wellbeing, Clarice Pears Building, 90 Byres Road, Glasgow, UK.
Khalid AlsallumiUniversity of Glasgow School of Health and Wellbeing, Clarice Pears Building, 90 Byres Road, Glasgow, UK.
John PetrieUniversity of Glasgow School of Health and Wellbeing, Clarice Pears Building, 90 Byres Road, Glasgow, UK.
Amanda AdlerDiabetes Trials Unit, University of Oxford, Oxford, UK.
Naveed SattarUniversity of Glasgow School of Cardiovascular and Metabolic Health, Glasgow, UK.
Daniel R MoralesPopulation Health and Genomics, School of Medicine, University of Dundee, Dundee, UK.
Bruce GuthrieUsher Institute, University of Edinburgh, Edinburgh, UK.
David McAllisterUniversity of Glasgow School of Health and Wellbeing, Clarice Pears Building, 90 Byres Road, Glasgow, UK.

Funding

Academy of Medical Sciences SGL029\1013Medical Research Council MR/T017112/1Medical Research Council MR/W006049/1Tenovus S22-27Wellcome TrustWellcome Trust 301005/Z/23/Z
6 · The paper itself

Abstract

backgroundRandomised controlled trials are often criticised for excluding people with multiple long-term conditions. This study used individual participant data for 25 trials of sodium glucose co-transporter-2 inhibitors (SGLT2i) to compare baseline characteristics, comorbidities, and event rates between trial participants and community SGLT2i-treated people in routine care.

methodsTrials were identified through systematic review with subsequent application for individual-level data. Community SGLT2i-treated people in routine care were identified from the Secure Anonymised Information Linkage (SAIL) databank (Wales, UK). For each trial, we applied the eligibility criteria to the community SGLT2i-treated populations. We then (i) assessed the proportion eligible/ineligible for each trial, (ii) compared age, sex and number of comorbidities between trial participants and those eligible/ineligible in routine care, (iii) compared rates of serious adverse events in the trials to the expected rate in community SGLT2i-treated participants and (iv) compared the rate of major adverse cardiovascular events (MACE), all-cause mortality, non-cardiovascular mortality, and estimated glomerular filtration rate (eGFR) slope between trial and community participants.

resultsThe number of comorbidities was consistently lower in trial populations compared to community SGLT2i-treated who met trial eligibility criteria. Compared with other trial populations, in the large cardiovascular outcome trials (CANVAS, CANVAS-R, CREDENCE and EMPA-REG) levels of participant comorbidity were higher; comorbidity differences between trial and community were smaller; and serious adverse event rates were broadly similar to the expected rate based on the community. For the remaining trials, the serious adverse event rate was lower in the trials than the expected rate based on community SGLT2i-treated participants. In the cardiovascular outcome trials, rates of MACE, mortality and decline in eGFR slope were similar or higher in trial populations.

conclusionsWhile people with comorbidity are under-represented in most trials compared to a Welsh routine care population, the large cardiovascular outcome trials are more representative of SGLT2i-treated patients and have similar rates of serious adverse events. Therefore, while our findings support calls for caution regarding trial representativeness, the criticism that trials are not representative does not apply equally to all trials. Our results broadly support the applicability of cardiovascular outcome trials to people currently treated with SGLT2i within routine clinical practice.

Indexed as

Diabetes Mellitus, Type 2Randomized Controlled Trials as TopicSodium-Glucose Transporter 2 InhibitorsAgedDatabases, FactualFemaleHumansMaleMiddle AgedSodium-Glucose Transporter 2 InhibitorsAdverse eventsApplicabilityComorbidityMultimorbidityRandomised controlled trialsRepresentativenessSodium Glucose Co-transporter 2 inhibitorsType 2 diabetes

Identifiers

PMID41299446
PMCPMC12659586

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Registered trials

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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.