Evidence map›Paper›PMID 42442791›Full record

SynthesisCMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne2026

Cardiovascular and renal outcomes of combined SGLT2 inhibitors and GLP-1 receptor agonists versus monotherapy in patients with type 2 diabetes mellitus: a network meta-analysis.

Min-Hsiang Chuang, Cheng-Wei Ho, Hsien-Yi Wang, Heng-Chih Pan, Vin-Cent Wu, Yu-Kang Tu, Jui-Yi Chen

Abstract readNetwork Meta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne, 2026. 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

7 authors.

Min-Hsiang ChuangDivision of Nephrology, Department of Internal Medicine (Chuang, Wang, Chen) and Department of Physical Medicine and Rehabilitation (Ho), Chi-Mei Medical Center, Tainan, Taiwan; Department of Sport Management (Wang), College of Leisure and Recreation Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan; Division of Nephrology, Department of Internal Medicine (Pan), Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; Division of Nephrology, Department of Internal Medicine (Wu), National Taiwan University Hospital, Taipei, Taiwan; Institute of Health Data Analytics and Statistics (Tu), College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Health and Nutrition (Chen), Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
Cheng-Wei HoDivision of Nephrology, Department of Internal Medicine (Chuang, Wang, Chen) and Department of Physical Medicine and Rehabilitation (Ho), Chi-Mei Medical Center, Tainan, Taiwan; Department of Sport Management (Wang), College of Leisure and Recreation Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan; Division of Nephrology, Department of Internal Medicine (Pan), Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; Division of Nephrology, Department of Internal Medicine (Wu), National Taiwan University Hospital, Taipei, Taiwan; Institute of Health Data Analytics and Statistics (Tu), College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Health and Nutrition (Chen), Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
Hsien-Yi WangDivision of Nephrology, Department of Internal Medicine (Chuang, Wang, Chen) and Department of Physical Medicine and Rehabilitation (Ho), Chi-Mei Medical Center, Tainan, Taiwan; Department of Sport Management (Wang), College of Leisure and Recreation Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan; Division of Nephrology, Department of Internal Medicine (Pan), Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; Division of Nephrology, Department of Internal Medicine (Wu), National Taiwan University Hospital, Taipei, Taiwan; Institute of Health Data Analytics and Statistics (Tu), College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Health and Nutrition (Chen), Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
Heng-Chih PanDivision of Nephrology, Department of Internal Medicine (Chuang, Wang, Chen) and Department of Physical Medicine and Rehabilitation (Ho), Chi-Mei Medical Center, Tainan, Taiwan; Department of Sport Management (Wang), College of Leisure and Recreation Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan; Division of Nephrology, Department of Internal Medicine (Pan), Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; Division of Nephrology, Department of Internal Medicine (Wu), National Taiwan University Hospital, Taipei, Taiwan; Institute of Health Data Analytics and Statistics (Tu), College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Health and Nutrition (Chen), Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
Vin-Cent WuDivision of Nephrology, Department of Internal Medicine (Chuang, Wang, Chen) and Department of Physical Medicine and Rehabilitation (Ho), Chi-Mei Medical Center, Tainan, Taiwan; Department of Sport Management (Wang), College of Leisure and Recreation Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan; Division of Nephrology, Department of Internal Medicine (Pan), Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; Division of Nephrology, Department of Internal Medicine (Wu), National Taiwan University Hospital, Taipei, Taiwan; Institute of Health Data Analytics and Statistics (Tu), College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Health and Nutrition (Chen), Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
Yu-Kang TuDivision of Nephrology, Department of Internal Medicine (Chuang, Wang, Chen) and Department of Physical Medicine and Rehabilitation (Ho), Chi-Mei Medical Center, Tainan, Taiwan; Department of Sport Management (Wang), College of Leisure and Recreation Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan; Division of Nephrology, Department of Internal Medicine (Pan), Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; Division of Nephrology, Department of Internal Medicine (Wu), National Taiwan University Hospital, Taipei, Taiwan; Institute of Health Data Analytics and Statistics (Tu), College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Health and Nutrition (Chen), Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
Jui-Yi ChenDivision of Nephrology, Department of Internal Medicine (Chuang, Wang, Chen) and Department of Physical Medicine and Rehabilitation (Ho), Chi-Mei Medical Center, Tainan, Taiwan; Department of Sport Management (Wang), College of Leisure and Recreation Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan; Division of Nephrology, Department of Internal Medicine (Pan), Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; Division of Nephrology, Department of Internal Medicine (Wu), National Taiwan University Hospital, Taipei, Taiwan; Institute of Health Data Analytics and Statistics (Tu), College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Health and Nutrition (Chen), Chia Nan University of Pharmacy and Science, Tainan, Taiwan. a50601@mail.chimei.org.tw.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundWhether using both sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) is more effective than using either alone in type 2 diabetes mellitus remains uncertain. We sought to assess cardiovascular and kidney outcomes of combined SGLT2i and GLP-1RA therapy versus monotherapy using network meta-analysis.

methodsWe identified randomized controlled trials (RCTs) of SGLT2i or GLP-1RA in patients with type 2 diabetes mellitus through a comprehensive search of MEDLINE, Embase, and the Cochrane Library until Aug. 15, 2025. We compared patients receiving SGLT2i, GLP-1RA, both SGLT2i and GLP-1RA, or neither medication in a systematic review and network meta-analysis. Primary outcomes were major adverse cardiovascular events (cardiovascular death, myocardial infarction, and stroke) and major adverse kidney events (decline in estimated glomerular filtration rate, kidney failure, and death due to kidney failure). Secondary outcomes included heart failure-related hospital admissions, serious adverse events, and hypoglycemia.

resultsWe included 12 RCTs with 99 683 participants. The risk of major adverse cardiovascular events did not differ significantly with combined SGLT2i and GLP-1RA therapy compared with SGLT2i (risk ratio [RR] 0.86, 95% confidence interval [CI] 0.74 to 1.01; very low certainty) or GLP-1RA alone (RR 0.95, 95% CI 0.81 to 1.12; very low certainty). Similarly, the risk of major adverse kidney events did not differ significantly with combined therapy from SGLT2i (RR 1.05, 95% CI 0.74 to 1.49; very low certainty) or GLP-1RA (RR 0.86, 95% CI 0.60 to 1.21; very low certainty). However, combined therapy was associated with a lower risk of heart failure-related hospital admission than SGLT2i (RR 0.72, 95% CI 0.52 to 0.99; very low certainty) or GLP-1RA (RR 0.62, 95% CI 0.45 to 0.86; very low certainty). Risks of serious adverse events or hypoglycemia did not differ significantly between combined therapy and monotherapy.

interpretationCompared with SGLT2i or GLP-1RA alone, combined therapy did not significantly reduce the risk of major adverse cardiovascular or kidney events but was associated with lower risks of heart failure-related hospital admission. Randomized controlled trials directly comparing combined therapy with monotherapy are needed to clarify the comparative effectiveness of combined therapy in patients with type 2 diabetes mellitus. PROTOCOL REGISTRATION: PROSPERO - CRD42024605727.

Indexed as

Cardiovascular DiseasesDiabetes Mellitus, Type 2Glucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsSodium-Glucose Transporter 2 InhibitorsDrug Therapy, CombinationHumansRandomized Controlled Trials as TopicGlucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsSodium-Glucose Transporter 2 Inhibitors

Identifiers

PMID42442791
PMCPMC13374707

What Socratic holds

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LicenceCC BY-NC-ND
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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 Socratic graph.