SGLT2 Inhibitors and GLP-1 Receptor Agonists in PAD: A State-of-the-Art Review

Area of Science:

• Cardiovascular Medicine
• Endocrinology
• Vascular Surgery

Background:

• Sodium-glucose co-transporter-2 inhibitors (SGLT2is) and GLP-1 receptor agonists (GLP-1 RAs) are vital for managing type 2 diabetes mellitus (T2DM).
• Early concerns regarding lower limb complications, including amputations, have created controversy surrounding their use in patients with peripheral artery disease (PAD).

Purpose of the Study:

• To critically evaluate the current evidence on the association between SGLT2is and GLP-1 RAs and PAD-related outcomes.
• To assess the safety and utility of these agents in individuals with PAD.
• To identify considerations for patient selection and future research directions.

Main Methods:

• Narrative review of existing literature.
• Inclusion of data from randomized controlled trials, real-world cohort studies, and systematic reviews.
• Analysis focused on limb events, amputation risk, and cardiovascular and renal endpoints in PAD patients.

Main Results:

• Evidence synthesis on the impact of SGLT2is and GLP-1 RAs on PAD outcomes.
• Integrated perspective on the safety profile concerning lower limb complications.
• Evaluation of cardiovascular and renal benefits in the context of PAD.

Conclusions:

• SGLT2is and GLP-1 RAs may offer significant benefits for T2DM patients with PAD, with current evidence suggesting a potentially lower risk of amputation than previously feared.
• Careful patient selection is crucial to optimize outcomes and mitigate any residual risks.
• Further research is warranted to fully elucidate the role of these therapies in PAD management.