Cardiovascular outcomes of type 2 diabetic patients treated with SGLT-2 inhibitors versus GLP-1 receptor agonists in real-life

Abstract

Introduction: Sodium glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) protect type 2 diabetic (T2D) patients from cardiovascular events, but no trial has directly compared their cardiovascular effects. We aimed to address this gap using real-world data.

Research design and methods: We performed a retrospective real-world study on a population of ~5 million inhabitants from North-East Italy. We identified T2D patients who received new prescription of SGLT2i or GLP-1RA from 2014 to 2018. SGLT2i and GLP-1RA initiators were matched 1:1 by propensity scores. The primary outcome was a composite of all-cause death, myocardial infarction, and stroke (three-point major adverse cardiovascular events (3P-MACE)). Secondary endpoints were each component of the primary endpoint, hospitalization for heart failure (HF), revascularization, hospitalization for cardiovascular causes, and adverse events.

Results: From a population of 330 193 diabetic patients, we followed 8596 SGLT2i and GLP-1RA matched initiators for a median of 13 months. Patients in both groups were on average 63 years old, 63% men, and 18% had pre-existing cardiovascular disease. T2D patients treated with SGLT2i versus GLP-1RA, experienced a lower rate of 3P-MACE (HR 0.68; 95% CI 0.61 to 0.99; p=0.043), myocardial infarction (HR 0.72; 95% CI 0.53 to 0.98; p=0.035), hospitalization for HF (HR 0.59; 95% CI 0.35 to 0.99; p=0.048), and hospitalization for cardiovascular causes (HR 0.82; 95% CI 0.69 to 0.99; p=0.037). Adverse events were not significantly different between the two groups.

Conclusions: In the absence of dedicated trials, this observational study suggests that SGLT2i may be more effective than GLP-1RA in improving cardiovascular outcomes of T2D.

Trial registration number: NCT04184947.

Keywords: cardiovascular system; glucagon-like peptide 1; observational study.

Conflict of interest statement

Competing interests: AA received research grants, lecture or advisory board fees from Merck Sharp & Dome, AstraZeneca, Novartis, Boeringher-Ingelheim, Sanofi, Mediolanum, Janssen, Novo Nordisk, Lilly, Servier, and Takeda. GPF received lecture fees or grant support from Abbott, AstraZeneca, Boehringer, Lilly, Merck-Sharp-Dome, Mundipharma, Novartis, Novo Nordisk, Sanofi, Servier.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Study flowchart. Visual description of the general framework of the study with sample size after each filtering step. GLP-1RA, glucagon-like peptide-1 receptor agonists; SGLT2i, sodium glucose cotransporter-2 inhibitors.

Figure 2

Outcome analysis. Results of Cox analysis on primary and secondary outcomes. Event rates are reported as number of events/1000 person-years. Top panel, AT analysis; bottom panel, ITT analysis. AT, as treated; CVD, cardiovascular disease; GLP-1RA, glucagon-like peptide-1 receptor agonists; ITT, intention to treat; SGLT2i, sodium glucose cotransporter-2 inhibitors; 3P-MACE, three-point major adverse cardiovascular events.

Figure 3

Outcome analysis by pre-existing CVD. Results of Cox analysis on primary and secondary outcomes, after stratification according to pre-existing CVD. In the figure, ‘p int.‘ refers to the interaction term (SGLT2i or GLP-1RA×CVD yes or no) in the adjusted model. CVD, cardiovascular disease; GLP-1RA, glucagon-like peptide-1 receptor agonists; N., number; SGLT2i, sodium glucose cotransporter-2 inhibitors; 3P-MACE, three-point major adverse cardiovascular events.