Cardiovascular outcomes with SGLT2 inhibitors versus DPP4 inhibitors and GLP-1 receptor agonists in patients with heart failure with reduced and preserved ejection fraction

Abstract

Background No study has compared the cardiovascular outcomes for sodium–glucose cotransporter-2 inhibitors (SGLT2i) head-to-head against other glucose-lowering therapies, including dipeptidyl peptidase 4 inhibitor (DDP4i) or glucagon-like peptide-1 receptor agonist (GLP-1RA)—which also have cardiovascular benefits—in patients with heart failure with reduced (HFrEF) or preserved (HFpEF) ejection fraction. Methods Medicare fee-for-service data (2013–2019) were used to create four pair-wise comparison cohorts of type 2 diabetes patients with: (1a) HFrEF initiating SGLT2i versus DPP4i; (1b) HFrEF initiating SGLT2i versus GLP-1RA; (2a) HFpEF initiating SGLT2i versus DPP4i; and (2b) HFpEF initiating SGLT2i versus GLP-1RA. The primary outcomes were (1) hospitalization for heart failure (HHF) and (2) myocardial infarction (MI) or stroke hospitalizations. Adjusted hazards ratios (HR) and 95% CIs were estimated using inverse probability of treatment weighting. Results Among HFrEF patients, initiation of SGLT2i versus DPP4i (cohort 1a; n = 13,882) was associated with a lower risk of HHF (adjusted Hazard Ratio [HR (95% confidence interval)], 0.67 (0.63, 0.72) and MI or stroke (HR: 0.86 [0.75, 0.99]), and initiation of SGLT2i versus GLP-1RA (cohort 1b; n = 6951) was associated with lower risk of HHF (HR: 0.86 [0.79, 0.93]), but not MI or stroke (HR: 1.02 [0.85, 1.22]). Among HFpEF patients, initiation of SGLT2i versus DPP4i (cohort 2a; n = 17,493) was associated with lower risk of HHF (HR: 0.65 [0.61, 0.69]) but not MI or stroke (HR: 0.90 [0.79, 1.02]), and initiation of SGLT2i versus GLP-1RA (cohort 2b; n = 9053) was associated with lower risk of HHF (0.89 [0.83, 0.96]), but not MI or stroke (HR: 0.97 [0.83, 1.14]). Results were robust across range of secondary outcomes (e.g., all-cause mortality) and sensitivity analyses. Conclusions Bias from residual confounding cannot be ruled out. Use of SGLT2i was associated with reduced risk of HHF against DPP4i and GLP-1RA, reduced risk of MI or stroke against DPP4i within the HFrEF subgroup, and comparable risk of MI or stroke against GLP-1RA. Notably, the magnitude of cardiovascular benefit conferred by SGLT2i was similar among patients with HFrEF and HFpEF.

Role of Liraglutide Use in Patients With Heart Failure

“…A 2023 analysis examined a cohort of older adults with heart failure (HFrEF or HFpEF) from Medicare data to compare the adjusted hazard ratios among those taking SGLT2i vs. GLP-1 agonists vs. DPP4i. There was no significant difference in the risk of MI or stroke among those taking SGLT2i or GLP-1 agonists [39].…”

Salvianolic acid B ameliorates myocardial fibrosis in diabetic cardiomyopathy by deubiquitinating Smad7

“…All interventions were administered by gavage 6 days/week. The ejection fraction (EF) of the control and DCM groups was assessed monthly, and the DCM model was successfully established when the EF of the DCM group was significantly lower than that of the control group [ 25 ].…”

Prevention and treatment of ischaemic and haemorrhagic stroke in people with diabetes mellitus: a focus on glucose control and comorbidities

“…In people with heart failure (HF) and diabetes, SGLT2 inhibitors seem to have a critical advantage in terms of the prevention of deterioration of cardiac function and hospitalisation compared with other treatments. In a large observational study, compared with GLP-1RAs, SGLT2 inhibitor use was associated with a significantly lower risk of hospitalisation for HF, ranging from 14% in people with HFrEF to 11% in those with HFpEF [ 93 ]. SGLT2 inhibitors were also superior to DPP-4 inhibitors in terms of hospitalisation for HF, with a 33% reduction in rate, but also in terms of myocardial infarction and stroke, with a 14% reduction in rates [ 93 ].…”

“…In a large observational study, compared with GLP-1RAs, SGLT2 inhibitor use was associated with a significantly lower risk of hospitalisation for HF, ranging from 14% in people with HFrEF to 11% in those with HFpEF [ 93 ]. SGLT2 inhibitors were also superior to DPP-4 inhibitors in terms of hospitalisation for HF, with a 33% reduction in rate, but also in terms of myocardial infarction and stroke, with a 14% reduction in rates [ 93 ]. Therefore, SGLT2 inhibitors are recommended as first-choice, independently of glucose control or other concomitant glucose-lowering treatment, in individuals with diabetes and HF, to reduce the rate of HF-related events.…”