Evidence map›Paper›PMID 39994802›Full record

ReviewDiabetology & metabolic syndrome2025

Safety, efficacy, and cardiovascular benefits of combination therapy with SGLT-2 inhibitors and GLP-1 receptor agonists in patients with diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

Asma Mousavi, Shayan Shojaei, Hamidreza Soleimani, Davood Semirani-Nezhad, Pouya Ebrahimi, Ali Zafari, Rasoul Ebrahimi, Khatere Roozbehi, Anil Harrison, Mushabbar A Syed and 5 more

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Diabetology & metabolic syndrome, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing 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.

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

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

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  19. Targeting Obesity for Heart Failure.European cardiology · 2025
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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

15 authors.

Asma MousaviCardiac Primary Prevention Research Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Shayan ShojaeiCardiac Primary Prevention Research Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Hamidreza SoleimaniCardiac Primary Prevention Research Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Davood Semirani-NezhadSchool of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran.
Pouya EbrahimiCardiac Primary Prevention Research Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Ali ZafariSchool of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Rasoul EbrahimiSchool of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Khatere RoozbehiSchool of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran.
Anil HarrisonInternal Medicine, Midwestern University, Arizona, USA.
Mushabbar A SyedLoyola University Stritch School of Medicine, Chicago, USA.
Toshiki KunoCardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Mani Khorsand AskariInternal Medicine, Department of Medicine, University of Toledo, Ohio, USA.
Jaime P AlmandozDepartment of Internal Medicine, Division of Endocrinology, UT Southwestern Medical Center, Dallas, TX, USA.
John JunDivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, College of Medicine and Life Sciences, University of Toledo, Ohio, USA.
Kaveh HosseiniCardiac Primary Prevention Research Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran. kaveh_hosseini130@yahoo.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe potential benefits and risks of combination therapy with sodium-glucose co-transporter-2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus monotherapy remain a subject of debate to optimize metabolic and cardiovascular outcomes in patients with type 2 diabetes mellitus. This study aims to systematically review and meta-analyze the available evidence from randomized controlled trials.

methodsA comprehensive search identified relevant randomized controlled trials comparing combination therapy with SGLT-2i and GLP-1RA to monotherapy or treatment as usual (TAU). The main outcome was the incidence of hospitalization for heart failure. Other outcomes included major adverse cardiovascular events (MACE) (cardiovascular mortality, all-cause mortality, stroke, and myocardial infarction), changes in metabolic parameters, and adverse events. Random-effects meta-analysis estimated risk ratios (RRs), mean difference (MD), and 95% confidence intervals (CIs). We assessed the risk of bias in included studies using the Cochrane ROB 2.0 tool.

resultsThe meta-analysis included 10 randomized controlled trials with 42,651 participants, of which 2,820 were on combination therapy and the rest on SGLT-2i (37.1%), GLP-1RA (20.1%) monotherapies or TAU (42.8%). Combination therapy had a lower risk of hospitalization for heart failure versus GLP-1RA monotherapy (RR = 0.37, 95% CI 0.22; 0.65), SGLT-2i monotherapy (RR = 0.37, 95% CI 0.19; 0.75), and TAU (RR = 0.43, 95% CI 0.24; 0.75), respectively. Combination therapy also had a significantly lower risk of MACE versus TAU (RR = 0.73, 95% CI 0.61; 0.88). Combination therapy showed greater weight loss and hemoglobin A1c reduction versus SGLT-2i monotherapy (MD = -2.20, 95% CI -3.09; -1.31 and MD = -0.74, 95% CI -1.21; -0.27), respectively, while no difference was noted versus GLP-1RA monotherapy. The incidence of nausea and diarrhea was higher with combination therapy versus SGLT-2i monotherapy (MD = 3.34, 95% CI 1.74; 6.43 and MD = 1.75, 95% CI 1.10; 2.77), respectively.

conclusionCombination therapy with SGLT-2i and GLP-1RA may provide superior cardiovascular, weight, and Hemoglobin A1c outcomes versus monotherapy despite higher gastrointestinal adverse events. These results may impact the management of patients with metabolic and cardiovascular diseases and highlight the need for further research on combination therapy to optimize outcomes.

Indexed as

Adverse eventsGLP-1RAHospitalization for heart failureMajor adverse cardiovascular eventsMetabolic outcomesSGTL-2i

Identifiers

PMID39994802
PMCPMC11849334

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.