SGLT2 inhibitors were better at reducing heart failure hospitalizations and had fewer hypoglycemic events, while GLP-1 agonists showed advantages for cardiovascular events and kidney outcomes in real-world data.
22,100 articles screenedComprehensive systematic review comparing SGLT2 inhibitors and GLP-1 agonists across real-world observational studies spanning 14 years
What the researchers found
From 22,100 research articles screened, the systematic review included observational studies comparing SGLT2 inhibitors and GLP-1 receptor agonists in real-world type 2 diabetes patients.
Key pooled analysis findings:
- Heart failure and MACE/revascularization risk ratios were slightly higher with SGLT2 inhibitors compared to GLP-1 agonists (meaning GLP-1 agonists had a slight edge for cardiovascular event reduction)
- Renal outcome odds ratios also slightly favored GLP-1 agonists
- However, SGLT2 inhibitors showed lower hypoglycemic events and lower all-cause mortality rates
- SGLT2 inhibitors were more effective specifically at reducing hospitalization for heart failure
The findings suggest these drug classes have complementary strengths rather than one being universally superior.
Why it matters
Both SGLT2 inhibitors and GLP-1 agonists are first-line options for type 2 diabetes with cardiovascular or kidney concerns. Understanding their real-world performance differences helps clinicians choose the right drug for each patient based on their specific risk profile — heart failure risk vs. cardiovascular event risk vs. kidney disease.
How the study worked
Systematic review following PRISMA guidelines. Researchers searched EMBASE, PubMed, ClinicalTrials.gov, and Cochrane Library for studies published from January 2010 to September 2024. Only observational (real-world) studies were included; randomized controlled trials were excluded to focus on real-world clinical outcomes. Pooled analysis calculated risk ratios and odds ratios for cardiovascular, renal, hypoglycemic, and mortality outcomes.
What this study cannot tell us
The review included only observational studies, which are subject to selection bias and confounding factors that randomized trials control for. The exclusion of RCTs means the findings may not establish causal relationships. Differences in study populations, drug doses, and follow-up periods across included studies could introduce heterogeneity. The review does not specify how many studies ultimately met inclusion criteria.
How to read the evidence
As a systematic review of observational studies, this provides broad real-world evidence synthesis. However, the deliberate exclusion of randomized controlled trials and reliance on observational data means the evidence is subject to confounding biases that limit causal conclusions.
When this study was published
Published in 2026 with data through September 2024, this is a very current review reflecting the latest real-world evidence on these widely prescribed drug classes.
The bigger picture
This review adds to the growing evidence supporting personalized medicine in diabetes care. Rather than viewing these drug classes as interchangeable, clinicians can now better match patients to the drug class that addresses their primary risk — a shift toward more targeted therapeutic decision-making in a disease affecting hundreds of millions worldwide.
Questions still open
- Would patients with both heart failure risk and cardiovascular event risk benefit from combining SGLT2 inhibitors with GLP-1 agonists?
- Do the relative advantages shift with longer treatment durations or in specific patient subgroups?
- How do newer dual-mechanism drugs like tirzepatide compare to either class alone?
Common questions
Should I take an SGLT2 inhibitor or a GLP-1 agonist for my type 2 diabetes?
Why did this review only look at real-world data instead of clinical trials?
Read the original research
Treatment outcomes and safety profile of SGLT2 inhibitors versus GLP-1 agonists in type 2 diabetes mellitus : Systematic review of real-world observational studies.
Wiener medizinische Wochenschrift (1946), 176(1-2), 45-59
Citation
Alam, Aftab; Imran, Mohd; Ur Rehman, Zia; Sahoo, Biswa Mohan; Mahapatra, Manoj Kumar. (2026). Treatment outcomes and safety profile of SGLT2 inhibitors versus GLP-1 agonists in type 2 diabetes mellitus : Systematic review of real-world observational studies.. Wiener medizinische Wochenschrift (1946), 176(1-2), 45-59. https://doi.org/10.1007/s10354-025-01108-5