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INTRODUCTION: Sodium-glucose co-transporter 2 inhibitors (SGLT2is) are licensed for the treatment of type 2 diabetes (T2D) and more recently for heart failure with or without diabetes. They have been shown to be safe (from the cardiovascular (CV) perspective) and effective (in terms of glycaemia, and in some cases, in reducing CV events) in extensive randomised controlled trials (RCTs). However, there remain concerns regarding the generalisability of these findings (to those ineligible for RCT participation) and about non-CV safety. For effectiveness, population-based pharmacoepidemiology studies can confirm and extend the findings of RCTs to broader populations and explore safety, for which RCTs are not usually powered, in more detail. METHODS: A pre-planned and registered ((International PROSPEctive Register Of Systematic Reviews) PROSPERO registration CRD42019160792) systematic review of population-based studies investigating SGLT2i effectiveness and safety, following Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines was conducted. RESULTS: A total of 37 studies were identified (total n = 1,300,184 adults; total follow-up 910,577 person-years; exposures: SGLT2i class, canagliflozin, dapagliflozin and empagliflozin) exploring CV disease (CVD) outcomes, acute kidney injury (AKI), lower limb amputation (LLA), diabetic ketoacidosis (DKA), bone fracture, urinary tract infection (UTI), genital mycotic infection (GMI), hypoglycaemia, pancreatitis and venous thromboembolism. For CV and mortality outcomes, studies confirmed the associated safety of these drugs and correlated closely with the findings from RCTs, which may extend to primary CVD prevention (major adverse cardiovascular events point estimate range (PER) hazard ratio (HR) 0.78-0.94; hospitalised heart failure PER HR 0.48-0.79). For safety outcomes, SGLT2i exposure was not associated with an increased risk of AKI (PER HR 0.40-0.96), fractures (PER HR 0.87-1.11), hypoglycaemia (PER HR 0.76-2.49) or UTI (PER HR 0.72-0.98). There was a signal for increased association for GMIs (PER HR 2.08-3.15), and possibly for LLA (PER HR 0.74-2.79) and DKA (PER HR 0.96-2.14), but with considerable uncertainty. CONCLUSION: In T2D, SGLT2is appear safe from the CV perspective and may have associated benefit in primary as well as secondary CVD prevention. For safety, they may be associated with an increased risk of GMI, LLA and DKA, although longer follow-up studies are needed.
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The Royal Air Force (RAF) came into being during World War I as the world's first independent air force on the 1 April 1918, amalgamating elements of the Royal Flying Corps (RFC), itself established in 1912 and the Royal Naval Air Service which had formally separated from the Admiralty's administered Air Wing of the RFC in 1915. The RAF therefore celebrates its 100th anniversary in the same year that the Royal College of Physicians of London celebrates its 500th. This article will cover the contribution that military aviation has made to medicine since 1913 with the emphasis of three examples focusing on delivering care by air, providing care in the air and in developing systems for supporting aircrew or patients at the extremes of physiological stress.