Comparison of treatment with insulin degludec and glargine U100 in patients with type 1 diabetes prone to nocturnal severe hypoglycaemia:The HypoDeg randomized, controlled, open-label, crossover trial

AIM: To investigate whether the long‐acting insulin analogue insulin degludec compared with insulin glargine U100 reduces the risk of nocturnal symptomatic hypoglycaemia in patients with type 1 diabetes (T1D). METHODS: Adults with T1D and at least one episode of nocturnal severe hypoglycaemia during the last 2 years were included in a 2‐year prospective, randomized, open, multicentre, crossover trial. A total of 149 patients were randomized 1:1 to basal‐bolus therapy with insulin degludec and insulin aspart or insulin glargine U100 and insulin aspart. Each treatment period lasted 1 year and consisted of 3 months of run‐in or crossover followed by 9 months of maintenance. The primary endpoint was the number of blindly adjudicated nocturnal symptomatic hypoglycaemic episodes. Secondary endpoints included the occurrence of severe hypoglycaemia. We analysed all endpoints by intention‐to‐treat. RESULTS: Treatment with insulin degludec resulted in a 28% (95% CI: 9%‐43%; P = .02) relative rate reduction (RRR) of nocturnal symptomatic hypoglycaemia at level 1 (≤3.9 mmol/L), a 37% (95% CI: 16%‐53%; P = .002) RRR at level 2 (≤3.0 mmol/L), and a 35% (95% CI: 1%‐58%; P = .04) RRR in all‐day severe hypoglycaemia compared with insulin glargine U100. CONCLUSIONS: Patients with T1D prone to nocturnal severe hypoglycaemia have lower rates of nocturnal symptomatic hypoglycaemia and all‐day severe hypoglycaemia with insulin degludec compared with insulin glargine U100

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

Adverse events of exercise therapy in randomised controlled trials: A systematic review and meta-analysis

Objective To evaluate the relative risk (RR) of serious and non-serious adverse events in patients treated with exercise therapy compared with those in a non-exercising control group. Design Systematic review and meta-analysis. Data sources Primary studies were identified based on The Cochrane Database of Systematic Reviews investigating the effect of exercise therapy. Eligibility criteria At least two of the authors independently evaluated all identified reviews and primary studies. Randomised controlled trials were included if they compared any exercise therapy intervention with a non-exercising control. Two authors independently extracted data. The RR of serious and non-serious adverse events was estimated separately. Results 180 Cochrane reviews were included and from these, 773 primary studies were identified. Of these, 378 studies (n=38 368 participants) reported serious adverse events and 375 studies (n=38 517 participants) reported non-serious adverse events. We found no increase in risk of serious adverse events (RR=0.96 (95%CI 0.90 to 1.02, I2: 0.0%) due to exercise therapy. There was, however, an increase in non-serious adverse events (RR=1.19 (95%CI 1.09 to 1.30, I2: 0.0%). The number needed to treat for an additional harmful outcome for non-serious adverse events was 6 [95%CI 4 to 11). Conclusion Participating in an exercise intervention increased the relative risk of non-serious adverse events, but not of serious adverse events. Exercise therapy may therefore be recommended as a relatively safe intervention

Adverse events of exercise therapy in randomised controlled trials: A systematic review and meta-analysis

Objective To evaluate the relative risk (RR) of serious and non-serious adverse events in patients treated with exercise therapy compared with those in a non-exercising control group. Design Systematic review and meta-analysis. Data sources Primary studies were identified based on The Cochrane Database of Systematic Reviews investigating the effect of exercise therapy. Eligibility criteria At least two of the authors independently evaluated all identified reviews and primary studies. Randomised controlled trials were included if they compared any exercise therapy intervention with a non-exercising control. Two authors independently extracted data. The RR of serious and non-serious adverse events was estimated separately. Results 180 Cochrane reviews were included and from these, 773 primary studies were identified. Of these, 378 studies (n=38 368 participants) reported serious adverse events and 375 studies (n=38 517 participants) reported non-serious adverse events. We found no increase in risk of serious adverse events (RR=0.96 (95%CI 0.90 to 1.02, I2: 0.0%) due to exercise therapy. There was, however, an increase in non-serious adverse events (RR=1.19 (95%CI 1.09 to 1.30, I2: 0.0%). The number needed to treat for an additional harmful outcome for non-serious adverse events was 6 [95%CI 4 to 11). Conclusion Participating in an exercise intervention increased the relative risk of non-serious adverse events, but not of serious adverse events. Exercise therapy may therefore be recommended as a relatively safe intervention