SynthesisJournal of the American Heart Association2017

Effect of Sodium-Glucose Cotransport-2 Inhibitors on Blood Pressure in People With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of 43 Randomized Control Trials With 22 528 Patients.

Mohsen Mazidi, Peyman Rezaie, Hong-Kai Gao, Andre Pascal Kengne

Registry-linked trialOpen access · goldAbstract readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in Journal of the American Heart Association, 2017. The graph read 5 numbers from its abstract, feeding 3 cells of the map: it supports the treatment in 2, finds no clear difference in 1. It is linked to trial NCT05556291 (Efficacy, Safety & Tolerability of Combination of Ertugliflozin and Sitagliptin in Patients With Type II Diabetes Mellitus), which is not on this map. Cited by 143 papers, 7 of them syntheses that pooled it.

5numbers the graph read from it
3cells of the map it votes in
143citing papers in PubMed, 7 pooled it
20.2field-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.

← favours the treatmentfavours the comparator →
-2.861.210 · no effect
Serum triglyceridesSGLT2 vs control (implied), in individuals with type 2 diabetes mellitusfavours the treatment · hypertension, obesityfeeds one cell of the map
Δ -2.08-2.51 to -1.64
In these subjects the weighted mean difference effects on serum triglycerides and total cholesterol were -2.08 mg/dL (95% CI -2.51 to -1.64) and 0.77 mg/dL (95% CI 0.33-1.21), respectively.
Total cholesterolSGLT2 vs control (implied), in individuals with type 2 diabetes mellitusfavours the comparator · hypertension, obesityfeeds one cell of the map
Δ 0.770.33 to 1.21
In these subjects the weighted mean difference effects on serum triglycerides and total cholesterol were -2.08 mg/dL (95% CI -2.51 to -1.64) and 0.77 mg/dL (95% CI 0.33-1.21), respectively.
Body weightSGLT2 vs control (implied), in individuals with type 2 diabetes mellitusfavours the treatment · hypertension, obesityfeeds one cell of the map
Δ -1.88-2.11 to -1.66
The weighted mean differences for the effect of SGLT2 on body weight was -1.88 kg (95% CI -2.11 to -1.66) across all studies.
Systolic BPSGLT2 vs control (implied), in individuals with type 2 diabetes mellitusfavours the treatment · hypertension, obesityfeeds one cell of the map
Δ -2.46-2.86 to -2.06
The meta-analysis indicated a significant reduction in systolic BP following treatment with SGLT2 (weighted mean difference -2.46 mm Hg [95% CI -2.86 to -2.06]).
Diastolic BPSGLT2 vs control (implied), in individuals with type 2 diabetes mellitusfavours the treatment · hypertension, obesityfeeds one cell of the map
Δ -1.46-1.82 to -1.09
The weighted mean differences for the effect on diastolic BP was -1.46 mm Hg (95% CI -1.82 to -1.09).

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.

SGLT2 inhibitors×lipids

InconclusiveOpen on the map →What to test next →

9 readable studies in this cell: 3 favour the treatment, 6 find no difference, 0 favour the comparator.

Belief with this paper
1.00replicated · 2 families support, 0 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
0 · no effect
NCT010326294,330 enrolled · 2009
Hodges-Lehman Estimate 0.02-0.04 to 0.07
NCT011066771,284 enrolled · 2010
Δ 2.30-3.90 to 8.50
NCT018093271,186 enrolled · 2013
Δ 5.301.20 to 9.50
NCT01137812756 enrolled · 2010
Δ -2.30-9.80 to 5.30
NCT01106651716 enrolled · 2010
Δ -4.80-12.1 to 2.50
NCT01081834678 enrolled · 2010
Δ -5.30-14.8 to 4.10
NCT01106625469 enrolled · 2010
Δ -6.20-16.9 to 4.50
NCT01106690344 enrolled · 2010
Δ -12.1-12.1 to -0.90

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

SGLT2 inhibitors×blood pressure

SupportsOpen on the map →What to test next →

38 readable studies in this cell: 24 favour the treatment, 14 find no difference, 0 favour the comparator.

Belief with this paper
0.88established · 14 families support, 2 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT010326294,330 enrolled · 2009
Δ -2.96-4.00 to -1.91
NCT011374742,996 enrolled · 2010
Δ -3.05-4.87 to -1.24
NCT011956622,245 enrolled · 2010
Δ -4.28-6.54 to -2.02
NCT011066771,284 enrolled · 2010
Δ -2.87-4.46 to -1.28
NCT020991101,233 enrolled · 2014
Δ -2.76-4.69 to -0.83
NCT018093271,186 enrolled · 2013
Δ -1.91-3.64 to -0.18
NCT02580591977 enrolled · 2015
Δ -2.10-3.90 to -0.20
NCT01042977964 enrolled · 2010
Δ -2.71-4.28 to -1.15
NCT03332771954 enrolled · 2017
Δ -4.18-6.70 to -1.65
NCT00984867833 enrolled · 2009
Δ -0.86-3.75 to 2.03
NCT03351478770 enrolled · 2017
Δ -2.05-4.87 to 0.76
NCT01137812756 enrolled · 2010
Δ -5.91-7.64 to -4.17

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

SGLT2 inhibitors×body weight & composition

SupportsOpen on the map →What to test next →

40 readable studies in this cell: 62 favour the treatment, 9 find no difference, 2 favour the comparator.

Belief with this paper
0.98established · 50 families support, 1 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT010326294,330 enrolled · 2009
Δ -2.96-3.47 to -2.45
NCT010956661,484 enrolled · 2010
Δ -1.10-1.65 to -0.56
NCT009688121,452 enrolled · 2009
Δ -5.20-5.70 to -4.70
NCT017190031,413 enrolled · 2012
Adjusted mean -2.50-3.33 to -1.68
NCT011066771,284 enrolled · 2010
Δ -2.40-3.00 to -1.80
NCT016060071,282 enrolled · 2012
Δ -2.05-2.73 to -1.37
NCT006732311,240 enrolled · 2008
Δ -1.00-1.50 to -0.49
NCT020991101,233 enrolled · 2014
Δ -1.85-2.48 to -1.22
NCT006609071,217 enrolled · 2008
Δ -4.65-5.14 to -4.17
NCT018093271,186 enrolled · 2013
Δ -0.90-1.60 to -0.20
NCT010956531,179 enrolled · 2010
Δ -1.37-2.01 to -0.73
NCT008598981,093 enrolled · 2009
Δ -1.97-2.64 to -1.30

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.

NCT05556291 completednot on this mapstarted 2022, after this paper: background citation

Efficacy, Safety & Tolerability of Combination of Ertugliflozin and Sitagliptin in Patients With Type II Diabetes Mellitus

TypeobservationalSponsorGetz PharmaRan2022 to 2024Enrolled190ConditionsEfficacy, Safety, TolerabilityArmsCombinations of Oral Blood Glucose Lowering Drugs
5 · Its place in the literature

Who cites it

143 citing papers in PubMed, 7 syntheses or guidelines pooled it, 346 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Trial
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  11. Long-term effects of ipragliflozin on blood pressure in patients with type 2 diabetes: insights from the randomized PROTECT trial.Hypertension research : official journal of the Japanese Society of Hypertension · 2024
    Trial
  12. Article
  13. Article
  14. Article
  15. Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. Review

83 more citing papers are in PubMed but not listed here.

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

4 authors at 4 institutions in 3 countries.

Mohsen MazidiKey State Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Peyman RezaieBiochemistry and Nutrition Research Center, School of Medicine, Mashhad University of Medical Science, Mashhad, Iran.
Hong-Kai GaoDepartment of General Surgery, The General Hospital of Chinese People's Armed Police Forces, Beijing, China moshen@genetics.ac.cn.
Andre Pascal KengneNon-Communicable Disease Research Unit, South African Medical Research Council and University of Cape Town, South Africa.
Chinese People's Armed Police ForceInstitute of Genetics and Developmental Biology · CNMashhad University of Medical Sciences · IRUniversity of Cape Town · ZA

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.

backgroundThe sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of oral hypoglycemic agents. We undertake a systematic review and meta-analysis of prospective studies to determine the effect of SGLT2 on blood pressure (BP) among individuals with type 2 diabetes mellitus. METHODS AND

resultsPubMed-Medline, Web of Science, Cochrane Database, and Google Scholar databases were searched to identify trial registries evaluating the impact of SGLT2 on BP. Random-effects models meta-analysis was used for quantitative data synthesis. The meta-analysis indicated a significant reduction in systolic BP following treatment with SGLT2 (weighted mean difference -2.46 mm Hg [95% CI -2.86 to -2.06]). The weighted mean differences for the effect on diastolic BP was -1.46 mm Hg (95% CI -1.82 to -1.09). In these subjects the weighted mean difference effects on serum triglycerides and total cholesterol were -2.08 mg/dL (95% CI -2.51 to -1.64) and 0.77 mg/dL (95% CI 0.33-1.21), respectively. The weighted mean differences for the effect of SGLT2 on body weight was -1.88 kg (95% CI -2.11 to -1.66) across all studies. These findings were robust in sensitivity analyses.

conclusionsTreatment with SGLT2 glucose cotransporter inhibitors therefore has beneficial off-target effects on BP in patients with type 2 diabetes mellitus and may also be of value in improving other cardiometabolic parameters including lipid profile and body weight in addition to their expected effects on glycemic control. However, our findings should be interpreted with consideration for the moderate statistical heterogeneity across the included studies.

Indexed as

Sodium-Glucose Transporter 2 InhibitorsAdministration, OralAdolescentAdultAgedAged, 80 and overBenzhydryl CompoundsBiomarkersBlood GlucoseBlood PressureBody WeightCanagliflozinDiabetes Mellitus, Type 2FemaleGlucosidesHumansBenzhydryl CompoundsBiomarkersBlood GlucoseCanagliflozindapagliflozinempagliflozinGlucosidesHypoglycemic AgentsipragliflozinLipidsSLC5A2 protein, humanSodium-Glucose Transporter 2Sodium-Glucose Transporter 2 InhibitorsThiophenesblood pressurediabetes mellitusmeta‐analysisSodium‐glucose cotransport‐2 inhibitors

Identifiers

PMID28546454
PMCPMC5669140
OpenAlexW2618856448

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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.