At the 58th Annual European Association for the Study of Diabetes (EASD) 2022 meeting in Stockholm, new results were presented from a subanalysis of the EMPEROR-Preserved trial. These results demonstrated the impact of Boehringer Ingelheim and Eli Lilly’s sodium-glucose co-transporter-2 (SGLT-2) inhibitor, empagliflozin (Jardiance), in reducing the need for insulin in patients with heart failure (HF) with preserved ejection faction (HFpEF) (ejection fraction >40%). It has been identified that type 2 diabetes (T2D) is highly prevalent among patients with HFpEF, leading to these patients requiring insulin therapy, and this new subanalysis presents the significance of clinical outcomes according to insulin use in the trial.
In recent years, there has been a significant evolution in the perspective that industry and clinicians have towards the SGLT-2 inhibitor class in the T2D treatment paradigm, as a barrage of clinical data has demonstrated that they are highly efficacious for treating cardiorenal disease. This has led to significant market uptake with physicians prescribing this therapy to patients with T2D and HF, and also patients with T2D and chronic kidney disease (CKD) (in the case of AstraZeneca’s dapagliflozin), as well as both HF and CKD in patients without T2D.
Specifically, empagliflozin has received market approval for systolic heart failure (EMA), cardiovascular risk factors (FDA), and chronic heart failure (Japan). Key opinion leaders interviewed by GlobalData have said that SGLT-2 inhibitors will increasingly be prescribed, as many T2D patients are presenting with complex comorbidities relating to cardiovascular risk, HF and CKD.
In total, 5,988 trial patients were randomised into the two arms of the study and given either empagliflozin 10mg or placebo. Of these, 2,938 (49%) had T2D and 1,980 (33%) had pre-diabetes mellitus (pre-DM) at baseline. The analysis covered the effects of empagliflozin versus placebo on the time to first sustained insulin initiation (≥2 consecutive study visits) in patients with T2D or pre-DM who were not using insulin at baseline. In addition, the analysis also covered the effect on the primary trial endpoint, first hospitalisation for heart failure or cardiovascular death (CV death) in patients with T2D at baseline according to the baseline subgroups of insulin use.
At baseline, 861 patients (434 in empagliflozin, 427 in placebo) were using insulin and patients using insulin were slightly younger (69.7 versus 71.5 years of age), had a longer diabetes duration (17.6 versus 9.4 years), lower eGFR (54.6 versus 61.9ml/min/1.73m²), and had more comorbidities such as coronary artery disease (47.3% versus 38.0%) and microalbuminuria (28.2% versus 11.2%). During a median observation time of 26 months, among patients with T2D or pre-DM not using insulin at baseline, empagliflozin reduced the risk of sustained initiation of insulin by 31% (hazard ratio [HR] 0.69 [95% confidence interval (CI), 0.49, 0.98], p=0.038). Among patients with T2D, those using insulin at baseline had high incidence rates of the primary endpoints, total HHFs, and first HHF (p-values for comparison within the placebo group: 0.0001).
With empagliflozin, it was observed that all patients in the EMPEROR trial had a reduced rate of insulin initiation, by 31% in patients with HFpEF and T2D or pre-diabetes. At baseline, insulin users had a significantly higher risk of adverse CV outcomes, and the effects of empagliflozin on CV outcomes were consistent in patients with T2D irrespective of insulin treatment. GlobalData predicts that the increasing positive data from the EMPEROR trial will establish empagliflozin as a dominant therapy for HF alongside dapagliflozin.