Liraglutide is an analogue of human glucagon-like peptide (GLP-1) approved for the treatment of type 2 diabetes. Although it has been shown to lower blood glucose and slightly reduce body weight and blood pressure, its long-term effects on cardiovascular outcomes have not been established. In this multicenter, double-blind, randomized control trial at 410 sites in 32 countries, 9340 patients with type 2 diabetes and high cardiovascular risk (at least 50 years old with hemoglobin A1c of 7.0% or more) were randomized in a 1:1 ratio to receive liraglutide or placebo to study the cardiovascular effects of liraglutide. With a median follow-up of 3.8 years, significantly fewer patients in the liraglutide group experienced the primary composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke (13.0% vs. 14.9%, HR 0.87, 95% CI: 0.78 to 0.97, p < 0.001). Significantly fewer patients taking liraglutide died from cardiovascular causes than in the placebo group (4.7% vs. 6.0%, HR 0.78, 95% CI: 0.66 to 0.93, p = 0.007). In addition, the death rate from any cause was lower in the liraglutide group (p = 0.02), and patients had nonsignificantly lower rates of nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, and incidents of pancreatitis. Thus, this time-to-event analysis demonstrates the positive effect of liraglutide on cardiovascular outcomes when added to diabetic patients’ standard of care.
While statin-based therapy is widely used to reduce the risk of coronary heart disease and stroke in patients with mild to moderate chronic kidney disease, previous studies investigating its effects on individuals with more advanced disease have been inconclusive. In this study, investigators ran a meta-analysis with individual participant data available from 28 trials (n = 183,419) from the Cholesterol Treatment Trailists’ Collaboration database, SHARP trial, and readjudicated deaths from the AURORA trial to study the effect statins have on major vascular events (non-fatal myocardial infarction or coronary death, stroke, or coronary revascularization) and mortality. It was found that statin-based therapy decreased the risk of a first major vascular event by 21% (RR 0.79, 95% CI: 0.77-0.81, p < 0.0001) per mmol/L reduction in LDL cholesterol. However, as patients’ eGFR declined, there was a trend towards smaller relative risk reductions in both major coronary events and strokes (p = 0.008 for trend; RR 0.78 for eGFR ≥60 mL/min per 1.73 m²; RR 0.76 for eGFR 45 to <60; RR 0.85 for eGFR 30 to <45; RR 0.85, 0·71–1·02 for eGFR <30 mL/min; and RR 0.94 for patients on dialysis). Results demonstrate that even with slightly smaller LDL reductions, there was little evidence statins can bring much benefit for patients with advanced chronic kidney disease, especially those already on dialysis.
Labor induction is an obstetrical intervention used to stimulate uterine contractions during pregnancy before labor begins on its own. Because it is commonly done for a variety of reasons including post-term pregnancy, placental abruption, oligohydramnios, and uterine infection, it would be greatly worrisome if reported associations between labor induction and increased risk of offspring autism spectrum disorders (ASD) reflected causality. In this retrospective cohort study, researchers reviewed all live births in Sweden from 1992-2005 as defined in the Medical Birth Register (n=1,362,950), of which 1.6% were diagnosed with ASD by ages 8 years through 21 years from 2001-2013 and 11% of deliveries were induced. In initial comparisons of individuals not related to one another, significant associations were found between labor induction and child ASD (HR 1.19, 95% CI: 1.13 to 1.24). However, when the study analyzed siblings whose births were discordant from the same mother (one sibling who had been induced and one not), this allowed for additional control for unmeasured factors within the family, and there no longer was an association (HR 0.99, 95% CI: 0.88 to 1.10). This new finding provides reassurance to mothers and suggests that concern about autism risk should not factor into clinical decisions about whether or not to induce labor.
The number of bariatric surgeries performed worldwide has risen sharply in recent years, but skepticism has been fueled by evidence of several negative long term effects, such as chronic kidney disease, relapse of type 2 diabetes, and reduced bone mineral density. In this retrospective, nested case-control study, investigators analyzed 12,676 patients who underwent bariatric surgery in Quebec, Canada between 2001-2014, using databases from the Quebec Integrated Chronic Diseases Surveillance System (QICDSS), age and sex matched with 38,028 obese and 126,760 non-obese controls. Bariatric patients were more likely to fracture both before and after surgery compared to non-operative obese and non-obese groups. Postoperative adjusted fracture risk was significantly higher as well (vs obese: RR 1.38, 95% CI: 1.23 to 1.55; vs. non-obese: RR 1.44, 95% CI: 1.29 to 1.59). Furthermore, fracture risk changed from a pattern associated with obesity before the operation to one typical of osteoporosis after. Proportion of fracture in distal lower limbs almost halved, proportion of distal upper limb fracture increased, and proportion of pelvis, hip, and femur fracture tripled. Therefore, fracture risk assessment is an important topic and should be incorporated for all bariatric surgery patients.
Sedentary behavior is a large part of many Americans’ daily lives and has been linked to a variety of deleterious chronic conditions and mortality. In this large systematic meta-analysis with data pulled from six databases (PubMed, PsycINFO, Embase, Web of Science, Sport Discus, Scopus), researchers examined the association of daily sitting time and physical activity with all-cause mortality, and again with TV-viewing time. 16 studies were included (n = 1,005,791) and followed up for 2-18 years. Mortality rates during follow-up were 12-59% higher for individuals belonging to the two lowest quartiles of physical activity, who either had <16 metabolic equivalent of task (MET)-hours per week of activity and sat <4 h/day, or had <2.5 MET-h per week and sat >8 h/day. In contrast, individuals who sat for >8 hours/day but also reported high levels of physical activity, >35.5 MET-h per week, did not have an increased risk of dying (HR 1.04, 95% CI: 0.99 to 1.10). Watching TV for 3 or more hours per day was associated with increased mortality regardless of physical activity, except in the most active quartile. This study suggests that while sedentary behavior is often unavoidable in today’s job world, engaging in about 60-75 minutes of moderate intensity physical activity on a daily basis may attenuate or even eliminate the increased mortality rate. Image: PD
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