Diabetes and Vascular Disease

SAT-587 - Comparative Cardiovascular and Renal Efficacy of Novel Glucose-Lowering Therapies in Type 2 Diabetes: An Umbrella Review of Meta-Analyses

Saturday, June 13, 2026

9:30 AM - 4:30 PM CT

Location: ENDOExpo; Poster Floor

Co-Author(s)

Samira Ali, MD

Corona, CA, United States
HS

Humaira Sadat Sultany, MD

Kabul University of Medical Sciences
Sayre, Pennsylvania, United States
NH

Nafisa Hamidi, MD

Bamyan provincial hospital
Fredericksburg, Virginia, United States
Hf

Hashmat faizi, MD

Nangarhar University
Portland, Oregon, United States
MS

Mohammad Ibrahim Sultani, Medical student

Ankara Yıldırım Beyazıt University Faculty of Medicine
Ankara, Turkey
MS

Mahjabin Shahid, MD

Kabul university of medical sciences
Annandale, Virginia, United States
MS

Marwa Sultani, Medical student

Ankara Yıldırım Beyazıt University Faculty of Medicine
Ankara, Turkey
RL

Roya Lalzai, MD

Kabul University of Medical Sciences-KUMS
Kabul, Afghanistan
SH

Sayed Sahil Hashemi, MD

Resident Medical Officer
The North Hospital , Melbourne, Australia
Epping, United States
MO

Mohammad Zahid Omerzad, MD

Kabul university of medical sciences
Kabul, Afghanistan

Abstract Poster Presenter(s)

SZ

Sundas Zahra, MD

Sayre, PA, United States

Disclosure(s):

Samira Ali, MD: No financial relationships to disclose

Background: Novel glucose-lowering therapies have demonstrated cardiovascular and renal benefits beyond glycemic control in type 2 diabetes mellitus (T2DM). However, comparative efficacy among sodium–glucose cotransporter-2 inhibitors (SGLT-2i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and dipeptidyl peptidase-4 inhibitors (DPP-4i) across major outcomes remains incompletely defined.

Methods: We conducted an umbrella review of meta-analyses of randomized controlled trials comparing SGLT-2i, GLP-1 RA, and DPP-4i with placebo or other glucose-lowering agents in adults with T2DM. PubMed, Embase, and Cochrane databases were searched from inception to December 2024. Outcomes included major adverse cardiovascular events (MACE), cardiovascular and all-cause mortality, myocardial infarction, stroke, hospitalization for heart failure (HHF), and renal outcomes. Methodological quality was assessed using AMSTAR-2 and certainty of evidence using GRADE.

Results: Nine meta-analyses were included. Both SGLT-2i and GLP-1 RA reduced MACE (SGLT-2i: HR 0.88–0.91, 95% CI 0.82–0.98; GLP-1 RA: HR 0.85–0.89, 95% CI 0.79–0.95), mainly in patients with established atherosclerotic cardiovascular disease. All-cause mortality was reduced with SGLT-2i (OR 0.82–0.85, 95% CI 0.70–0.96) and GLP-1 RA (OR 0.87–0.88, 95% CI 0.79–0.95), as was cardiovascular mortality (SGLT-2i: OR 0.82, 95% CI 0.70–0.95; GLP-1 RA: OR 0.87, 95% CI 0.79–0.95). SGLT-2i demonstrated superior reduction in HHF (OR 0.65–0.69, 95% CI 0.59–0.79) compared with GLP-1 RA (OR 0.93–0.95, 95% CI 0.83–1.06). GLP-1 RA reduced stroke risk (OR 0.87, 95% CI 0.77–0.98), whereas SGLT-2i showed no significant effect (OR 1.12, 95% CI 0.92–1.36). Renal benefits were greater with SGLT-2i, reducing composite kidney outcomes by 38–45% (HR 0.55–0.62, 95% CI 0.48–0.67) and hard renal endpoints (HR 0.55, 95% CI 0.48–0.64), while GLP-1 RA effects were largely driven by albuminuria reduction (OR 0.61, 95% CI 0.44–0.84). DPP-4i showed neutral cardiovascular effects. Real-world data (3,157,259 patients) supported SGLT-2i benefits on MACE (OR 0.71), all-cause mortality (OR 0.53), and HHF (OR 0.56).

Conclusions: SGLT-2i and GLP-1 RA provide complementary cardiovascular and renal benefits with distinct profiles. SGLT-2i are preferred for heart failure and chronic kidney disease, while GLP-1 RA may be favored for stroke prevention.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*