SGLT2 inhibitors

Trial registry update: COMPLETED. No results reported in the supplied registry record.

This retrospective cohort study of 230 AMI-PCI patients with preserved ejection fraction (LVEF ≥50%) compared outcomes in those prescribed SGLT2 inhibitors versus no SGLT2 inhibitors. After propensity score matching, SGLT2i use was associated with lower rates of new-onset heart failure (6.09% vs 15.65%), all-cause mortality (3.48% vs 10.43%), cardiovascular mortality (1.74% vs 9.57%), and MACE (7.83% vs 18.26%) over at least 18 months follow-up.

In a US cohort of 99,738 patients hospitalized for heart failure (mean age 78 years), early empagliflozin initiation (during hospitalization or within 7 days post-discharge) was associated with lower 1-year all-cause mortality (RR 0.73) compared to delayed or no initiation, with absolute 1-year mortality of 24.7% versus 33.6%. Early initiation was also associated with reduced worsening HF events (RR 0.89), HF rehospitalizations (RR 0.86), ED visits (RR 0.87), and all-cause hospitalizations (RR 0.91).

Using propensity score-matched Medicare claims data (2014-2020), this real-world analysis compared adults aged ≥65 with type 2 diabetes who initiated empagliflozin versus dipeptidyl peptidase-4 inhibitors or GLP-1 receptor agonists. Empagliflozin was associated with lower rates of major adverse cardiovascular events (HR 0.77), hospitalization for heart failure (HR 0.72), and all-cause mortality (HR 0.66) versus DPP4 inhibitors, with consistent effects across sociodemographic subgroups but greater absolute benefits in those with prevalent cardiovascular disease.

This post-hoc analysis of the EMPEROR-Pooled RCT examined 9706 heart failure patients randomised to empagliflozin or placebo, measuring baseline neutrophil-to-lymphocyte ratio (NLR) and clinical outcomes. Patients in the highest NLR quintile had higher rates of heart failure hospitalisation or cardiovascular death (27.3% vs 14.9%, adjusted HR 1.44) compared to the lowest quintile. Empagliflozin's beneficial effects on primary and secondary outcomes were consistent across all NLR quintiles, and the drug did not reduce elevated NLR during follow-up.

This observational study examined whether urinary glucose (glucosuria) could serve as a marker of adherence to SGLT2 inhibitors and whether it correlated with clinical outcomes in routine clinical practice. No sample size or effect sizes were reported in the available information.

A cross-trial aggregate-data meta-analysis combined hazard ratios from six Phase III randomised trials to estimate the effect of quintuple disease-modifying therapy (including ACE inhibitors/ARBs, beta-blockers, aldosterone antagonists, SGLT2 inhibitors, and vericiguat) versus conventional therapy in heart failure with reduced ejection fraction. The imputed combined effect showed HR 0.34 (95% CI 0.27–0.42) for cardiovascular death or first heart failure hospitalisation, HR 0.31 for first HF hospitalisation alone, HR 0.47 for cardiovascular death alone, and HR 0.51 for all-cause mortality.

This systematic review examined pharmacological interventions targeting aging pathways, including metformin, from literature published January 2010–May 2026. Metformin and rapamycin had among the most extensive preclinical and translational evidence, but the review found that clinical evidence for broadly applicable geroprotection remains limited. The authors emphasize a substantial gap between mechanistic plausibility and clinically validated geroprotection in humans.

This retrospective cohort study of 15,052 patients (7,526 matched pairs) undergoing major cardiac procedures compared preoperative SGLT2 inhibitor users to non-users. SGLT2 inhibitor use was associated with reduced all-cause mortality at 30 days (1.3% vs 2.3%, RR 0.566), 90 days (2.2% vs 3.4%, RR 0.643), and 1 year (3.8% vs 5.8%, RR 0.657), and with lower acute kidney injury at 30 days (15.4% vs 17.7%, RR 0.870), but higher hospital readmission rates (76.4% vs 68.7%, RR 1.111).