SynthesisBMC endocrine disorders2022

Systematic review and meta-analysis of head-to-head trials comparing sulfonylureas and low hypoglycaemic risk antidiabetic drugs.

Vallo Volke, Urmeli Katus, Annika Johannson, Karolin Toompere, Keiu Heinla, Kertu Rünkorg, Anneli Uusküla

Open access · goldFull text readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in BMC endocrine disorders, 2022. The graph read 4 numbers from its abstract, feeding 2 cells of the map, but none could be read as for or against, so it casts no vote. Cited by 11 papers.

4numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.9field-weighted citation impact, top 8% 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.

Read, but not usablea number the graph found but could not read as for or against

All-cause mortalitycomparator not stated · t2dfeeds one cell of the map
OR 1.321.07 to 1.61
In comparison to drugs with low hypoglycaemic potential, sulfonylureas had higher odds for all-cause mortality (OR 1.32, 95% CI 1.00-1.75), MACE (OR 1.32, 95% CI 1.07-1.61), myocardial infarction (fatal and non-fatal) (OR 1.67, 95% CI 1.17-2.38) and hypoglycaemia (OR 5.24, 95% CI 4.20-6.55).
All-cause mortalitycomparator not stated · t2dfeeds one cell of the map
OR 1.321.00 to 1.75
In comparison to drugs with low hypoglycaemic potential, sulfonylureas had higher odds for all-cause mortality (OR 1.32, 95% CI 1.00-1.75), MACE (OR 1.32, 95% CI 1.07-1.61), myocardial infarction (fatal and non-fatal) (OR 1.67, 95% CI 1.17-2.38) and hypoglycaemia (OR 5.24, 95% CI 4.20-6.55).
Cardiovascular eventscomparator not stated · t2dfeeds one cell of the map
OR 5.244.20 to 6.55
In comparison to drugs with low hypoglycaemic potential, sulfonylureas had higher odds for all-cause mortality (OR 1.32, 95% CI 1.00-1.75), MACE (OR 1.32, 95% CI 1.07-1.61), myocardial infarction (fatal and non-fatal) (OR 1.67, 95% CI 1.17-2.38) and hypoglycaemia (OR 5.24, 95% CI 4.20-6.55).
Cardiovascular eventscomparator not stated · t2dfeeds one cell of the map
OR 1.671.17 to 2.38
In comparison to drugs with low hypoglycaemic potential, sulfonylureas had higher odds for all-cause mortality (OR 1.32, 95% CI 1.00-1.75), MACE (OR 1.32, 95% CI 1.07-1.61), myocardial infarction (fatal and non-fatal) (OR 1.67, 95% CI 1.17-2.38) and hypoglycaemia (OR 5.24, 95% CI 4.20-6.55).

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.

Sulfonylureas & glinides×all-cause mortality

No readable resultOpen on the map →What to test next →

No other readable study in this cell yet. This paper is the evidence.

Belief with this paperNo claim has been compiled for this cell yet.

Sulfonylureas & glinides×cardiovascular events

No readable resultOpen on the map →What to test next →

3 readable studies in this cell: 2 favour the treatment, 1 find no difference, 0 favour the comparator.

Belief with this paper
0.96replicated · 2 families support, 0 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
1 · no effect

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

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

11 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Review
  3. Novel Small Molecule GLP-1R Agonists Based on 1Molecules (Basel, Switzerland) · 2026
    Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Cardiometabolic Risk Factors Associated With Type 2 Diabetes Mellitus: A Mechanistic Insight.Clinical medicine insights. Endocrinology and diabetes · 2023
    Review
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

7 authors at 1 institution in 1 country.

Vallo VolkeDepartment of Physiology, Institute of Biomedicine and Translational Medicine, Centre of excellence in Genomics and Translational Medicine, University of Tartu, 19 Ravila Street, 50411, Tartu, Estonia. vallo.volke@ut.ee.
Urmeli KatusDepartment of Family Medicine and Public Health, University of Tartu, Tartu, Estonia.
Annika JohannsonDepartment of Family Medicine and Public Health, University of Tartu, Tartu, Estonia.
Karolin ToompereDepartment of Family Medicine and Public Health, University of Tartu, Tartu, Estonia.
Keiu HeinlaDepartment of Physiology, Institute of Biomedicine and Translational Medicine, Centre of excellence in Genomics and Translational Medicine, University of Tartu, 19 Ravila Street, 50411, Tartu, Estonia.
Kertu RünkorgDepartment of Physiology, Institute of Biomedicine and Translational Medicine, Centre of excellence in Genomics and Translational Medicine, University of Tartu, 19 Ravila Street, 50411, Tartu, Estonia.
Anneli UuskülaDepartment of Family Medicine and Public Health, University of Tartu, Tartu, Estonia.
University of Tartu · EE

Funding

Estonian Ministry of Education and Research IUT34-17
8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

backgroundSafety of sulfonylurea drugs in the treatment of Type 2 Diabetes is still under debate. The aim of this study was to compare the all-cause mortality and cardiovascular adverse events of sulfonylureas and drugs with a low risk for hypoglycaemia in adults with type 2 diabetes.

methodsSystematic review and meta-analysis of randomised controlled trials. DATA SOURCES: MEDLINE (PubMed, OVID), Embase, Cochrane Central Register of Controlled Trials, CINAHL, WOS and Lilacs. STUDY SELECTION: Randomised controlled head-to-head trials that compared sulfonylureas with active control with low hypoglycaemic potential in adults (≥ 18 years old) with type 2 diabetes published up to August 2015. The drug classes involved in the analysis were metformin, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose co-transporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists. OUTCOMES: The primary endpoint was all-cause mortality. The secondary endpoints were MACE, cardiovascular events and severe hypoglycaemia. SYNTHESIS OF

resultsTwo reviewers checked study eligibility, independently extracted data and assessed quality with disagreements resolved through discussion. We assessed the risk of bias of the included studies using the Cochrane risk of bias tool for randomized trials v2. Pooled odds ratios (ORs) were estimated by using fixed effects model. The study is registered on PROSPERO (26/05/2016 CRD42016038780).

resultsOur final analysis comprised 31 studies (26,204 patients, 11,711 patients given sulfonylureas and 14,493 given comparator drugs). In comparison to drugs with low hypoglycaemic potential, sulfonylureas had higher odds for all-cause mortality (OR 1.32, 95% CI 1.00-1.75), MACE (OR 1.32, 95% CI 1.07-1.61), myocardial infarction (fatal and non-fatal) (OR 1.67, 95% CI 1.17-2.38) and hypoglycaemia (OR 5.24, 95% CI 4.20-6.55). Subsequent sensitivity analysis revealed differences in the effect of sulfonylureas, with an increased risk of all-cause mortality with glipizide but not the other molecules.

conclusionOur meta-analysis raises concern about the safety of SUs compared to alternative drugs involved in current analysis. Important differences may exist within the drug class, and glimepiride seems to have best safety profile.

Indexed as

Diabetes Mellitus, Type 2Dipeptidyl-Peptidase IV InhibitorsHypoglycemiaMetforminSodium-Glucose Transporter 2 InhibitorsSymportersAdolescentAdultDipeptidyl-Peptidases and Tripeptidyl-PeptidasesGlipizideGlucagon-Like Peptide 1GlucoseHumansHypoglycemic AgentsSodiumDipeptidyl-Peptidase IV InhibitorsDipeptidyl-Peptidases and Tripeptidyl-PeptidasesGlipizideGlucagon-Like Peptide 1GlucoseHypoglycemic AgentsMetforminSodiumSodium-Glucose Transporter 2 InhibitorsSymportersAll-cause mortalityDiabetes mellitusHypoglycemic therapyMACESulfonylurea

Identifiers

PMID36261824
PMCPMC9580135
OpenAlexW4306784291

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.