Patients with type 2 diabetes who took SGLT2 inhibitors had a 21% lower risk of developing peripheral artery disease compared to those on DPP4 inhibitors, while GLP-1 receptor agonists showed similar protection to SGLT2 inhibitors.
21% lower PAD riskSGLT2 inhibitors vs DPP4 inhibitors over a median 5.6-year follow-up in 75,470 type 2 diabetes patients
What the researchers found
In a propensity-matched cohort of 75,470 patients with type 2 diabetes followed for a median of 5.6 years, SGLT2 inhibitor users had a significantly lower risk of new-onset peripheral artery disease compared to DPP4 inhibitor users (HR 0.79, 95% CI 0.66–0.93). In a three-arm analysis, the risk of PAD was not statistically different between SGLT2 inhibitors and GLP-1 receptor agonists (HR 1.18, 95% CI 0.52–2.68), suggesting both newer drug classes offer similar vascular protection. The findings remained consistent across subgroups regardless of sex, age, or comorbid metabolic diseases.
Why it matters
Peripheral artery disease is a major cause of disability and amputation in diabetes patients. This large real-world study suggests that choosing SGLT2 inhibitors or GLP-1 receptor agonists over DPP4 inhibitors may provide additional vascular protection, potentially influencing treatment selection for patients at risk of PAD.
The numbers in context
n=75,470 · SGLT2I: 28,753 · DPP4I: 46,717 · PAD HR 0.79 (SGLT2I vs DPP4I) · 95% CI 0.66–0.93 · median follow-up 5.6 years · GLP-1 RA vs SGLT2I HR 1.18 (not significant)
How the study worked
Retrospective population-based cohort study using a territory-wide electronic health database from Hong Kong. Patients with type 2 diabetes prescribed SGLT2 inhibitors or DPP4 inhibitors between January and December 2015 were included. Propensity score matching (1:1) was used to balance baseline characteristics. Multivariable Cox regression with time-weighted variables identified associations. A three-arm analysis added a GLP-1 receptor agonist cohort. Competing risk and sensitivity analyses were performed.
Who was studied
Adults with type 2 diabetes in Hong Kong who were prescribed SGLT2 inhibitors, DPP4 inhibitors, or GLP-1 receptor agonists between 2015 and follow-up
What this study cannot tell us
This is an observational study, so it cannot prove causation — only association. The GLP-1 receptor agonist cohort was much smaller, resulting in wide confidence intervals for that comparison. As a Hong Kong-based study, the predominantly Chinese population may limit generalizability. Residual confounding from unmeasured variables is possible despite propensity matching.
How to read the evidence
Large population-based cohort study with propensity score matching and multiple sensitivity analyses. However, as a retrospective observational study, it cannot establish causation. The GLP-1 receptor agonist comparison was underpowered.
When this study was published
Published in 2025 using 2015–2021 data, this study reflects contemporary prescribing patterns and provides timely evidence for current clinical decision-making.
The bigger picture
This study adds to growing evidence that newer diabetes medications — particularly SGLT2 inhibitors and GLP-1 receptor agonists — offer cardiovascular benefits beyond glucose control. As peripheral artery disease remains undertreated in diabetes, these findings could help guide medication selection for patients at vascular risk.
Questions still open
- Would a head-to-head randomized trial between GLP-1 receptor agonists and SGLT2 inhibitors confirm equivalent PAD protection?
- What is the mechanism by which these drug classes protect against peripheral artery disease — is it purely metabolic or also anti-inflammatory?
- Should PAD risk be factored into diabetes medication selection algorithms alongside cardiovascular and renal risk?
Common questions
What is peripheral artery disease and why is it a concern in diabetes?
How do DPP4 inhibitors relate to peptides?
Read the original research
Comparison of New-Onset Peripheral Artery Disease in Patients With Type 2 Diabetes Exposed to Sodium-Glucose Cotransporter-2 Inhibitors, Dipeptidyl Peptidase-4 Inhibitors, or Glucagon-Like Peptide-1 Agonists: A Population-Based Cohort Study.
Journal of the American Heart Association, 14(11), e034175
Citation
Chou, Oscar Hou-In; Luo, Zhiyao; Chung, Cheuk To Skylar; Chan, Jeffrey; Li, Huixian; Lakhani, Ishan; Lee, Sharen; Lau, Dawnie Ho Hei; Zhang, Qingpeng; Liu, Tong; Wong, Wing Tak; Cheung, Bernard Man Yung; Lip, Gregory Y H; Leung, Fung Ping; Tse, Gary; Zhou, Jiandong. (2025). Comparison of New-Onset Peripheral Artery Disease in Patients With Type 2 Diabetes Exposed to Sodium-Glucose Cotransporter-2 Inhibitors, Dipeptidyl Peptidase-4 Inhibitors, or Glucagon-Like Peptide-1 Agonists: A Population-Based Cohort Study.. Journal of the American Heart Association, 14(11), e034175. https://doi.org/10.1161/JAHA.123.034175