Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

Abstract BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .)

The outcomes of patients with diabetes mellitus in The Philippine CORONA Study

Patients diagnosed with diabetes mellitus (DM) who are infected with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) belong to the most vulnerable patient subgroups. Emerging data has shown increased risks of severe infections, increased in ICU admissions, longer durations of admission, and increased mortality among coronavirus disease 2019 (COVID-19) patients with diabetes. We performed a subgroup analysis comparing the outcomes of patients diagnosed with DM (n = 2191) versus patients without DM (n = 8690) on our data from our study based on a nationwide, comparative, retrospective, cohort study among adult, hospitalized COVID-19 patients involving 37 hospital sites from around the Philippines. We determined distribution differences between two independent samples using Mann–Whitney U and t tests. Data on the time to onset of mortality, respiratory failure, intensive care unit (ICU) admission were used to build Kaplan–Meier curves and to compute for hazard ratios (HR). The odds ratios (OR) for longer ventilator dependence, longer ICU stay, and longer hospital stays were computed via multivariate logistic regression. Adjusted hazard ratios (aHR) and ORs (aOR) with 95% CI were calculated. We included a total of 10,881 patients with confirmed COVID-19 infection (2191 have DM while 8690 did not have DM). The median age of the DM cohort was 61, with a female to male ratio of 1:1.25 and more than 50% of the DM population were above 60 years old. The aOR for mortality was significantly higher among those in the DM group by 1.46 (95% CI 1.28–1.68; p \u3c 0.001) as compared to the non-DM group. Similarly, the aOR for respiratory failure was also significantly higher among those in the DM group by 1.67 (95% CI 1.46–1.90). The aOR for developing severe COVID-19 at nadir was significantly higher among those in the DM group by 1.85 (95% CI 1.65–2.07; p \u3c 0.001). The aOR for ICU admission was significantly higher among those in the DM group by 1.80 (95% CI 1.59–2.05) than those in the non-DM group. DM patients had significantly longer duration of ventilator dependence (aOR 1.33, 95% CI 1.08–1.64; p = 0.008) and longer hospital admission (aOR 1.13, 95% CI 1.01–1.26; p = 0.027). The presence of DM among COVID-19 patients significantly increased the risk of mortality, respiratory failure, duration of ventilator dependence, severe/critical COVID-19, ICU admission, and length of hospital stay