Effects of SGLT-2 inhibitors on diabetic ketoacidosis: A meta-analysis of randomised controlled trials.

AIMS: Diabetic ketoacidosis (DKA) associated with SGLT-2 inhibitors (SGLT-2i) is a possible adverse event. In fact, SGLT-2i are capable of stimulating the release of glucagon and ketone re-absorption in the renal tubuli, thus increasing the concentration of ketone bodies. METHODS: A Medline search for SGLT2i (dapagliflozin, empagliflozin, canagliflozin, ipragliflozin, ertugliflozin, luseogliflozin) was performed, collecting all randomized trials with a duration of treatment≥12weeks, enrolling patients with type 2 diabetes, and comparing a SGLT2i with placebo or other comparators. The principal outcome was the effect of SGLT2i on ketoacidosis as serious adverse event. RESULTS: Out of 72 trials reporting information on DKA, 9 reported at least one event of ketoacidosis; those eight trials enrolled 10,157 and 5396 in SGLT-2 inhibitors and comparator groups, respectively. No signal of increased risk for ketoacidosis was observed for SGLT2 inhibitors as a class (MH-OR [95% CI] 1.14 [0.45-2.88], p=0.78) or as individual molecule. The sensitivity analysis with continuity correction (inputing one event each in drug and comparator arms of each trial with zero events) suggested a reduced incidence of ketoacidosis in patients treated with SGLT-2 inhibitors (MH-OR 0.65 [0.47-0.90]; p=0.01). CONCLUSIONS: The results of clinical trials summarized in the present meta-analysis reassure us that, when the drug is properly prescribed, the risk of DKA is negligible.

Preliminary results of an early vs delayed timing of surgery in the management of proximal femur fragility fractures.

INTRODUCTION: The appropriate surgical timing for the treatment of proximal femur fractures is still debated. Advantages of a delayed surgery may be: stabilization of systemic diseases, decrease of the risk of perioperative mortality and morbidity. An early timing of surgery may allow: early mobilization, reduction of the risks of disability and hospital stays, early return to home of the patients. However, the effects on mortality are still discussed. PURPOSE: The purpose of this study is to assess the influence of the surgical timing on clinical outcomes, complications, and mortality in a preliminary experience of the early management of these fractures vs the delayed surgery. METHODS: A series of 176 patients was retrospectively evaluated. 132 patients were followed-up for one year after surgery. The evaluation was performed by the assessment of the comorbidities, preoperative wait for surgery, type of fracture and procedures, hospital stay, and functional outcomes: 33 patients were operated with an early timing, 99 with a delayed surgery. RESULTS: The mean mortality rate was 18.2% in the early timing (6/33 patients), and 23.2% in the delayed timing (23/99 patients): no significant difference was recorded in the preliminary analysis. Postoperative complications were recorded in 28 patients (21.2%): 4 patients were operated within 48 hours (12.1%) and 24 after 48 hours (24.2%) with no substantial differences. The postoperative hospital stay showed no correlation with the timing of surgery, as no evidence was found on the functional recovery and postoperative disability. CONCLUSIONS: No significant differences were found on the evaluated parameters in the two groups in the present preliminary study. A correlation between male sex and mortality, and male sex and postoperative complications was assessed. An enlargement of the study population is needed to surely clarify any effective differences, given the fact that recent studies seem to identify in the early treatment the better strategy to ensure the best recovery and the lower rate of mortality and complications.