SynthesisAmerican journal of cardiovascular drugs : drugs, devices, and other interventions2025

Cardiovascular Safety Profile of Semaglutide and Variations by Sex, Race, and Kidney Function: A Systematic Review and Meta-analysis.

Muhammad Hamayal, Chaudhary Humayun Akhtar, Naveed Ahmad, Muhammad Awwab, Warda Shahid, Hasan Shaukat Abbasi, Esha Nadeem, Erum Siddiqui, Wadana Zafar, Saima Hussain

Abstract readSystematic ReviewMeta-Analysis
PubMed Publisher
In one paragraph

Synthesis in American journal of cardiovascular drugs : drugs, devices, and other interventions, 2025. The graph read 3 numbers from its abstract, feeding 1 cell of the map: it supports the treatment in 1. Not yet cited in PubMed.

3numbers the graph read from it
1cell 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.

← favours the treatmentfavours the comparator →
1 · no effect
Major adverse cardiovascular events (MACE)semaglutide vs placebo, in patients with established or a risk of cardiovascular diseasefavours the treatment · ascvd, t2dfeeds one cell of the map
RR 0.810.74 to 0.88p < 0.00001
The risk of MACE with semaglutide was significantly lower in patients with established or a risk of cardiovascular disease (risk ratio [RR] 0.81; 95% confidence interval [CI] 0.74-0.88; p < 0.00001).

The authors add: null

Major adverse cardiovascular events (MACE)semaglutide vs placebo, in malesfavours the treatment · ascvd, t2dfeeds one cell of the map
RR 0.780.70 to 0.87p < 0.00001
MACE risk reduction was significant in males (RR 0.78; 95% CI 0.70-0.87; p < 0.00001) and in Asian (RR 0.61; 95% CI 0.44-0.83; p = 0.002) and white (RR 0.82; 95% CI 0.73-0.90; p = 0.0001) populations.

The authors add: null

Expanded MACEsemaglutide vs placebo, in all patientsfavours the treatment · ascvd, t2dfeeds one cell of the map
RR 0.800.75 to 0.86p < 0.00001
The risk of expanded MACE also reduced significantly with semaglutide (RR 0.80; 95% CI 0.75-0.86; p < 0.00001).

The authors add: null

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.

GLP-1 receptor agonists×cardiovascular events

SupportsOpen on the map →What to test next →

13 readable studies in this cell: 7 favour the treatment, 2 find no difference, 4 favour the comparator.

Belief with this paper
0.50contested · 7 families support, 3 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
1 · no effect
NCT0399313226,774 enrolled · 2018
HR 1.010.91 to 1.11
NCT0357459717,604 enrolled · 2018
HR 0.800.72 to 0.89
NCT013949529,901 enrolled · 2011
HR 0.880.79 to 0.99
NCT039143269,651 enrolled · 2019
HR 0.860.77 to 0.96
NCT011790489,341 enrolled · 2010
HR 0.870.78 to 0.97
NCT038191533,533 enrolled · 2019
HR 0.760.66 to 0.88
NCT017204463,297 enrolled · 2013
HR 0.740.58 to 0.95
NCT026927163,183 enrolled · 2017
HR 0.790.57 to 1.11
OR 1.951.28 to 3.00
NCT05564039282 enrolled · 2022
OR 20.48.40 to 49.8

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Muhammad HamayalAl-Farabi Center, Federal Medical and Dental College, Hanna Road, G-8/4, Islamabad, 44080, Pakistan.ORCID http://orcid.org/0009-0005-4908-4844
Chaudhary Humayun AkhtarAl-Farabi Center, Federal Medical and Dental College, Hanna Road, G-8/4, Islamabad, 44080, Pakistan.
Naveed AhmadAl-Farabi Center, Federal Medical and Dental College, Hanna Road, G-8/4, Islamabad, 44080, Pakistan.
Muhammad AwwabQuaid-e-Azam Medical College, Circular Road, Bahawalpur, 06318, Pakistan.
Warda ShahidAl-Farabi Center, Federal Medical and Dental College, Hanna Road, G-8/4, Islamabad, 44080, Pakistan. wardashahid198@gmail.com.ORCID http://orcid.org/0009-0009-5954-8461
Hasan Shaukat AbbasiAl-Farabi Center, Federal Medical and Dental College, Hanna Road, G-8/4, Islamabad, 44080, Pakistan.
Esha NadeemAl-Farabi Center, Federal Medical and Dental College, Hanna Road, G-8/4, Islamabad, 44080, Pakistan.
Erum SiddiquiJinnah Sindh Medical University, Rafiqui H.J, Iqbal Shaheed Rd, Karachi Cantonment, Karachi, 75510, Pakistan.
Wadana ZafarKhyber Medical College, University of Peshawar, Road No. 2, Peshawar, 25120, Pakistan.
Saima HussainUniversity of Regina Saskatoon, The Concourse, Innovation Place, Saskatoon, SK, S7N 3R3, Canada.

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 mellitus and its complications are at increased risk for cardiovascular diseases. Semaglutide is efficacious for glycemic control and reducing the risk of major adverse cardiovascular outcomes. Although trials have provided data about cardiovascular outcomes with this agent, a meta-analysis regarding its cardiovascular safety and variations in outcomes according to sex, race and estimated glomerular filtration rate was necessary. MATERIALS AND

methodsWe searched the PubMed, Cochrane Library, and Clinicaltrials.gov databases and included randomized controlled trials (RCTs) where semaglutide was the intervention and major adverse cardiovascular events (MACE) or expanded MACE was the outcome. We assessed the quality of the RCTs using the Cochrane Risk of Bias tool and used the statistical software RevMan 5.4. The protocol for this review was registered on PROSPERO (CRD42024580784).

resultsOf 5387 articles, four RCTs were included. The risk of MACE with semaglutide was significantly lower in patients with established or a risk of cardiovascular disease (risk ratio [RR] 0.81; 95% confidence interval [CI] 0.74-0.88; p < 0.00001). The risk of expanded MACE also reduced significantly with semaglutide (RR 0.80; 95% CI 0.75-0.86; p < 0.00001). MACE risk reduction was significant in males (RR 0.78; 95% CI 0.70-0.87; p < 0.00001) and in Asian (RR 0.61; 95% CI 0.44-0.83; p = 0.002) and white (RR 0.82; 95% CI 0.73-0.90; p = 0.0001) populations.

conclusionSemaglutide provides significant advantages in terms of lowering the risk of MACE and expanded MACE and could possibly be used as a crucial component of cardiovascular risk management, particularly in populations that respond well, such as men and Asian and white populations. REGISTRATION: PROSPERO identifier number CRD42024580784.

Indexed as

Cardiovascular DiseasesDiabetes Mellitus, Type 2Glucagon-Like PeptidesHypoglycemic AgentsFemaleGlomerular Filtration RateGlucagon-Like Peptide 1HumansMaleRacial GroupsRandomized Controlled Trials as TopicSemaglutideSex FactorsGlucagon-Like Peptide 1Glucagon-Like PeptidesHypoglycemic AgentsSemaglutide

Identifiers

What Socratic holds

Texttitle and abstract
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.