SynthesisJournal of diabetes2023

Noninsulin-based antihyperglycemic medications in patients with diabetes and COVID-19: A systematic review and meta-analysis.

Mahmoud Nassar, Hazem Abosheaishaa, Awadhesh Kumar Singh, Anoop Misra, Zachary Bloomgarden

Full text readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in Journal of diabetes, 2023. The graph read 7 numbers from its abstract, feeding 5 cells of the map: it supports the treatment in 1, favours the comparator in 1. It also reports 3 associations that do not count as treatment evidence, such as RR 0.79 (0.69 to 0.89) for adverse events & safety. Cited by 14 papers, 2 of them syntheses that pooled it.

7numbers the graph read from it
2cells of the map it votes in
14citing papers in PubMed, 2 pooled it
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.

← favours the treatmentfavours the comparator →
1 · no effect
Adverse events & safetyfavours the treatment · against placebo · t2dfeeds one cell of the map
RR 0.890.84 to 0.95p < .001
There was a statistically significant decrease in hospitalization for SGLT-2i users vs nonusers (RR: 0.89, 95% CI: 0.84-0.95, p < .001).
Adverse events & safetyfavours the comparator · against placebo · t2dfeeds one cell of the map
RR 1.241.04 to 1.48p < .02
Dipeptidyl peptidase-4 inhibitor (DPP-4i) use was associated with statistically significantly higher hospitalization risk (RR: 1.44, 95% CI: 1.23, 1.68, p < .001) and higher risk of ICU admissions and/or mechanical ventilation vs nonusers (RR: 1.24, 95% CI: 1.04, 1.48, p < .02).
Adverse events & safetyfavours the comparator · against placebo · t2dfeeds one cell of the map
RR 1.441.23 to 1.68p < .001
Dipeptidyl peptidase-4 inhibitor (DPP-4i) use was associated with statistically significantly higher hospitalization risk (RR: 1.44, 95% CI: 1.23, 1.68, p < .001) and higher risk of ICU admissions and/or mechanical ventilation vs nonusers (RR: 1.24, 95% CI: 1.04, 1.48, p < .02).

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

Adverse events & safetyan association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
RR 0.560.42 to 73.0p < 0.001
Glucagon-like peptide-1 receptor agonist (GLP-1RA) use was associated with a statistically significant decrease in mortality (RR: 0.56, 95% CI: 0.42, 073, p < 0.001), ICU admission, and/or mechanical ventilation (RR: 0.79, 95% CI: 0.69-0.89, p < .001), and hospitalization (RR: 0.73, 95% CI: 0.54, 0.98, p = .04).
Adverse events & safetyan association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
RR 0.790.69 to 0.89p < .001
Glucagon-like peptide-1 receptor agonist (GLP-1RA) use was associated with a statistically significant decrease in mortality (RR: 0.56, 95% CI: 0.42, 073, p < 0.001), ICU admission, and/or mechanical ventilation (RR: 0.79, 95% CI: 0.69-0.89, p < .001), and hospitalization (RR: 0.73, 95% CI: 0.54, 0.98, p = .04).
Adverse events & safetyan association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
RR 0.730.54 to 0.98p = .04
Glucagon-like peptide-1 receptor agonist (GLP-1RA) use was associated with a statistically significant decrease in mortality (RR: 0.56, 95% CI: 0.42, 073, p < 0.001), ICU admission, and/or mechanical ventilation (RR: 0.79, 95% CI: 0.69-0.89, p < .001), and hospitalization (RR: 0.73, 95% CI: 0.54, 0.98, p = .04).
All-cause mortalityan association or prognostic statement, not a treatment comparison · t2dfeeds 2 cells of the map
RR 0.600.47 to 0.77p < .001
RESULTS: The use of metformin rather than other glucose-lowering medications was associated with statistically significant lower mortality (risk ratio [RR]: 0.60, 95% confidence interval [CI]: 0.47, 0.77, p < .001).

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.

DPP-4 inhibitors×adverse events & safety

SupportsOpen on the map →What to test next →

34 readable studies in this cell: 12 favour the treatment, 17 find no difference, 5 favour the comparator.

Belief with this paper
0.00contested · 0 families support, 19 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
0 · no effect
NCT040178321,441 enrolled · 2019
Δ -0.20-0.30 to -0.10
NCT020991101,233 enrolled · 2014
Δ -3.20-11.7 to 5.50
NCT019301881,231 enrolled · 2013
Δ -1.06-1.21 to -0.91
NCT007344741,202 enrolled · 2008
Δ -0.71-0.87 to -0.55
NCT022730501,136 enrolled · 2014
Δ 0.00-2.30 to 2.30
NCT004499301,050 enrolled · 2007
Δ -7.30-10.6 to -4.20
NCT008389031,049 enrolled · 2009
Δ -0.35-0.53 to -0.17
NCT01023581784 enrolled · 2009
Δ -0.57-0.87 to -0.27
NCT01682759751 enrolled · 2012
Δ -6.90-13.9 to 0.10
NCT02738879746 enrolled · 2016
Δ -2.10-9.10 to 5.00
NCT01217073685 enrolled · 2010
Δ 6.20-6.20 to 18.4
NCT01890122647 enrolled · 2013
Δ -0.49-0.70 to -0.28

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

SGLT2 inhibitors×adverse events & safety

ContradictsOpen on the map →What to test next →

38 readable studies in this cell: 18 favour the treatment, 19 find no difference, 1 favour the comparator.

Belief with this paper
0.00contested · 0 families support, 26 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT011374742,996 enrolled · 2010
Δ -0.46-0.59 to -0.33
NCT017190031,413 enrolled · 2012
Adjusted mean -0.33-0.56 to -0.10
NCT020991101,233 enrolled · 2014
Δ 1.40-7.40 to 10.1
NCT018093271,186 enrolled · 2013
Δ -0.46-0.66 to -0.27
NCT01649297983 enrolled · 2012
Δ -0.61-0.79 to -0.44
NCT02580591977 enrolled · 2015
Δ -0.28-0.46 to -0.11
NCT02414958730 enrolled · 2015
Δ -0.54-0.66 to -0.41
NCT01381900678 enrolled · 2011
Δ -0.51-0.64 to -0.37
NCT02033889621 enrolled · 2013
Δ 1.50-2.10 to 5.40
NCT02532855614 enrolled · 2015
Δ -2.80-10.7 to 5.10
NCT02630706506 enrolled · 2015
Δ -6.00-16.5 to 4.60
NCT02036515464 enrolled · 2014
Δ -5.70-16.5 to 5.20

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

GLP-1 receptor agonists×adverse events & safety

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

40 readable studies in this cell: 47 favour the treatment, 14 find no difference, 2 favour the comparator.

Belief with this paper
0.02contested · 1 family supports, 41 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT017204463,297 enrolled · 2013
Δ -0.66-0.80 to -0.52
NCT036893742,274 enrolled · 2018
Δ -0.29-0.38 to -0.20
NCT013360231,663 enrolled · 2011
Treatment contrast -0.64-0.75 to -0.53
NCT040178321,441 enrolled · 2019
Δ -0.20-0.30 to -0.10
NCT018365231,398 enrolled · 2013
Δ -0.20-0.32 to -0.07
NCT019301881,231 enrolled · 2013
Δ -1.06-1.21 to -0.91
NCT007344741,202 enrolled · 2008
Δ -0.71-0.87 to -0.55
NCT008389031,049 enrolled · 2009
Δ -0.91-1.16 to -0.65
NCT009606611,036 enrolled · 2009
Δ -0.04-0.18 to 0.11
NCT050350821,018 enrolled · 2021
Δ -0.24-0.44 to -0.04
NCT01064687978 enrolled · 2010
Δ -1.05-1.22 to -0.88
NCT01117350978 enrolled · 2010
Δ 2.54-3.88 to 8.93

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

Metformin×all-cause mortality

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

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

Belief with this paper
0.50one trial · 1 family supports, 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
NCT000387272,779 enrolled · 1996
HR 0.990.79 to 1.25

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

Other glucose-lowering×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 paper
0.00contested · 0 families support, 1 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
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

14 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. 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

5 authors.

Mahmoud NassarDepartment of Medicine, Icahn School of Medicine at Mount Sinai/NYC Health+Hospitals/Queens, New York City, New York, USA.ORCID https://orcid.org/0000-0002-5401-9562
Hazem AbosheaishaaDepartment of Medicine, Icahn School of Medicine at Mount Sinai/NYC Health+Hospitals/Queens, New York City, New York, USA.ORCID https://orcid.org/0000-0002-5581-8702
Awadhesh Kumar SinghDepartment of Diabetes & Endocrinology, GD Hospital & Diabetes Institute, Kolkata, India.ORCID https://orcid.org/0000-0002-8374-4536
Anoop MisraChairman, Fortis-C-DOC Centre of Excellence for Diabetes, Metabolic Diseases and Endocrinology, Diabetes Foundation (India), and National Diabetes Obesity and Cholesterol Foundation (NDOC), New Delhi, India.ORCID https://orcid.org/0000-0001-5785-5833
Zachary BloomgardenDepartment of Medicine, Division of Endocrinology, Diabetes and Bone Disease, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

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.

backgroundPatients with diabetes are more likely to suffer COVID-19 complications. Using noninsulin antihyperglycemic medications (AGMs) during COVID-19 infection has proved challenging. In this study, we evaluate different noninsulin AGMs in patients with COVID-19.

methodsWe searched Medline, Embase, Web of Science, and Cochrane on 24 January 2022. We used the following keywords (COVID-19) AND (diabetes mellitus) AND (antihyperglycemic agent). The inclusion criteria were studies reporting one or more of the outcomes. We excluded non-English articles, case reports, and literature reviews. Study outcomes were mortality, hospitalization, and intensive care unit (ICU) admission.

resultsThe use of metformin rather than other glucose-lowering medications was associated with statistically significant lower mortality (risk ratio [RR]: 0.60, 95% confidence interval [CI]: 0.47, 0.77, p < .001). Dipeptidyl peptidase-4 inhibitor (DPP-4i) use was associated with statistically significantly higher hospitalization risk (RR: 1.44, 95% CI: 1.23, 1.68, p < .001) and higher risk of ICU admissions and/or mechanical ventilation vs nonusers (RR: 1.24, 95% CI: 1.04, 1.48, p < .02). There was a statistically significant decrease in hospitalization for SGLT-2i users vs nonusers (RR: 0.89, 95% CI: 0.84-0.95, p < .001). Glucagon-like peptide-1 receptor agonist (GLP-1RA) use was associated with a statistically significant decrease in mortality (RR: 0.56, 95% CI: 0.42, 073, p < 0.001), ICU admission, and/or mechanical ventilation (RR: 0.79, 95% CI: 0.69-0.89, p < .001), and hospitalization (RR: 0.73, 95% CI: 0.54, 0.98, p = .04).

conclusionsAGM use was not associated with increased mortality. However, metformin and GLP-1RA use reduced mortality risk statistically significantly. DPP-4i use was associated with a statistically significant increase in the risk of hospitalization and admission to the ICU.

Indexed as

COVID-19Diabetes Mellitus, Type 2Dipeptidyl-Peptidase IV InhibitorsMetforminSodium-Glucose Transporter 2 InhibitorsGlucagon-Like Peptide-1 ReceptorHumansHypoglycemic AgentsDipeptidyl-Peptidase IV InhibitorsGlucagon-Like Peptide-1 ReceptorHypoglycemic AgentsMetforminSodium-Glucose Transporter 2 InhibitorsCOVID-19diabetesDPP-4 inhibitorsDPP-4抑制剂GLP-1RAoral antihyperglycemicSGLT-2 inhibitorsSGLT-2抑制剂sulfonylureasthiazolidinediones口服降糖药物噻唑烷二酮类新型冠状病毒肺炎磺脲类糖尿病

Identifiers

PMID36690377
PMCPMC9934962

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.