A Novel Cardioprotective Therapy That Also Improves Glycemia

Abstract

The profound effects of sodium-glucose transporter 2 (SGLT2) inhibition on the risks of cardiovascular complications in patients with hyperglycemia have provided for rapid and substantive changes to diabetes guidelines from various countries. In this issue of JAMA, Petrie and colleagues 1 report findings from a highly informative exploratory analysis of the most recent large-scale clinical trial of an SGLT2 inhibitor that may suggest the next chapter for this drug class-the transition from a glucose-lowering therapy that provides cardioprotection to a cardioprotective agent that happens to lower blood glucose.The main results of the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial were reported in 2019, and it was the first large-scale trial of an SGLT2 inhibitor designed specifically to assess the effects of the drug on clinical cardiovascular end points in patients with heart failure. 2 The high-quality trial showed definitive evidence of protection against a broad range of cardiovascular and kidney complications for patients with heart failure and reduced ejection fraction (HFrEF). The results confirmed and extended benefits anticipated from secondary analyses of the 4 prior large-scale outcome trials conducted in a broader set of patients with diabetes. 3 In addition to the specific focus on patients with heart failure at baseline, the design feature of the DAPA-HF trial that distinguished it from its predecessors was the inclusion, for the first time, of patients without diabetes at enrollment. In the present report in JAMA, Petrie et al 1 defined the effects of SGLT2 inhibition on various outcomes among patients with diabetes vs those without diabetes. The investigators enrolled 4744 patients with HFrEF from 410 sites in 20 countries. 1 Patients were eligible if they met the following criteria: aged 18 years or older; New York Heart Association class II, III, or IV symptoms; an ejection fraction of 40% or less; and an elevated level of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP). The majority of participants (2605 [55%]) had no history of diabetes at baseline.Patients were randomized to receive 10 mg of dapagliflozin daily (n = 2373 [1075 with type 2 diabetes]) or matched placebo (n = 2371 [1064 with type 2 diabetes]). Patients were followed up for a median of 18 months, and the primary outcome was a composite of worsening heart failure or cardiovascular death. Among patients with diabetes, the primary outcome occurred in 215 of 1075 patients (20.0%) in the dapagliflozin group and 271 of 1064 patients (25.5%) in the placebo group (hazard ratio, 0.75 [95% CI, 0.63-0.90]); among participants without diabetes, the primary outcome occurred in 171 of 1298 (13.2%) patients in the dapagliflozin group and 231

Cardiometabolic medicine: a review of the current proposed approaches to revamped training in the United States

“…These specialists must then rely on their organ-system-specific training from fellowship and continuing medical education (CME), which may not adequately prepare physicians to address every aspect of the cardiometabolic patient [6,7]. Furthermore, skills, such as counseling on lifestyle behavior modification and management of novel cardiometabolic medications, such as sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, remain focal points where physician uptake can be improved through training [8][9][10][11][12]. Currently, it is not clear which specialist will oversee the management of these medications, and as a result, they might never be initiated [13].…”