Empagliflozin was effective at reducing risk for cardiovascular and renal events among patients with diabetes and cardiovascular disease (CVD) comorbidities. These findings, from a randomized trial, were published in Diabetes Care.
Investigators recruited patients (N=7020) with type 2 diabetes who had established CVD and an estimated glomerular filtration rate (eGFR) of at least 30 mL/min/1.73 m2 for this study. They randomly assigned participants to receive 10 or 25 mg empagliflozin or a placebo daily and assessed patients for obstructive sleep apnea (OSA) at baseline and follow-up (median, 3.1 years).
At baseline, 5.6% of participants had OSA. Patients with OSA differed from patients without OSA by sex (82.9% vs 70.8% men), body mass index (55.2% vs 18.8% ³35 kg/m2), prevalence of coronary artery disease (88% vs 74.9%), insulin use (647.3% vs 4.2%), and rate of antihypertensive therapy (98.5% vs 94.8%).
Among the placebo group, baseline OSA was associated with poorer clinical outcomes. The rate of 3-point major adverse cardiovascular events (MACE) at study conclusion was 1.2- to 2-fold higher among patients with OSA (6.49/100 person years [PY]) compared with no OSA (4.27/100 PY). Patients with OSA had elevated rates of cardiovascular death (2.57 vs 1.99/100 PY), hospitalization for heart failure (2.71 vs 1.38/100 PY), all-cause mortality (4.29 vs 2.78/100 PY), worsening nephropathy (9.16 vs 7.52/100 PY), and macroalbuminuria progression (9.08 vs 6.36/100 PY) compared with patients with no OSA, respectively.
At study conclusion, empagliflozin treatment reduced rates of MACE (hazard ratio [HR] 0.86; 95% CI, 0.74-0.99; P =.04), cardiovascular death (HR 0.62; 95% CI, 0.49-0.77; P <.0001), hospitalization for heart failure (HR 0.65; 95% CI, 0.5-0.85; P =.0017), all-cause mortality (HR 0.68; 95% CI, 0.57-0.82; P <.0001), worsening nephropathy (HR 0.61; 95% CI, 0.53-0.71; P <.001), and macroalbuminuria progression (HR 0.62; 95% CI, 0.54-0.7; P <.001).
Patients with baseline OSA had larger magnitude of benefit from treatment (HR 0.32; 95% CI, 0.17-0.6) compared with no OSA (HR 0.65; 95% CI, 0.56-0.75; P =.0312). At 108 weeks, patients receiving empagliflozin with OSA had a larger reduction of body mass index (adjusted mean, −3.1±0.6 kg) than no OSA (adjusted mean, −2±0.1 kg).
New-onset OSA was 52% less likely among the treatment group compared with the placebo cohort (HR 0.48; 95% CI, 0.27-0.83). The investigators observed that of the risk for new-onset OSA, empagliflozin accounted for 22.4%; weight, 16.5%; hemoglobin, 12.2%; hematocrit, 9.4%; and systolic blood pressure, 8.9%.
This study may have been limited by its definition of OSA, which was defined by patient or investigator reporting and not through a polysomnography. The observed rates were lower than what was expected in the general population.
The study authors concluded that patients with diabetes, CVD, and OSA were at increased risk for poorer clinical outcomes than patients without OSA. Empagliflozin showed clinically relevant decreases of CV risk factors among all patients and decreased risk of developing OSA.
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of authors’ disclosures.
Neeland I J, Eliasson B, Kasai T, et al; EMPA-REG OUTCOME Investigators. The impact of empagliflozin on obstructive sleep apnea, cardiovascular, and renal outcomes: an exploratory analysis of the EMPA-REG OUTCOME Trial. Diabetes Care. 2020;dc201096.