The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the prior position statements, published in 2012 and 2015, on the management of type 2 diabetes in adults. A systematic evaluation of the literature since 2014 informed new recommendations. These include additional focus on lifestyle management and diabetes self-management education and support. For those with obesity, efforts targeting weight loss, including lifestyle, medication, and surgical interventions, are recommended. With regards to medication management, for patients with clinical cardiovascular disease, a sodium–glucose cotransporter 2 (SGLT2) inhibitor or a glucagon-like peptide 1 (GLP-1) receptor agonist with proven cardiovascular benefit is recommended. For patients with chronic kidney disease or clinical heart failure and atherosclerotic cardiovascular disease, an SGLT2 inhibitor with proven benefit is recommended. GLP-1 receptor agonists are generally recommended as the first injectable medication.

The obstructive sleep apnea syndrome significantly increases the risk of stroke or death from any cause, and the increase is independent of other risk factors, including hypertension.

The aim of this updated guideline is to provide comprehensive and timely evidence-based recommendations on the prevention of future stroke among survivors of ischemic stroke or transient ischemic attack. The guideline is addressed to all clinicians who manage secondary prevention for these patients. Evidence-based recommendations are provided for control of risk factors, intervention for vascular obstruction, antithrombotic therapy for cardioembolism, and antiplatelet therapy for noncardioembolic stroke. Recommendations are also provided for the prevention of recurrent stroke in a variety of specific circumstances, including aortic arch atherosclerosis, arterial dissection, patent foramen ovale, hyperhomocysteinemia, hypercoagulable states, antiphospholipid antibody syndrome, sickle cell disease, cerebral venous sinus thrombosis, and pregnancy. Special sections address use of antithrombotic and anticoagulation therapy after an intracranial hemorrhage and implementation of guidelines.

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Kleindorfer et al2021 Guideline for the Secondary Prevention of Ischemic Stroke AdherenceA key component of secondary stroke prevention is assessing and addressing barriers to adherence to medications and a healthy lifestyle. If a patient has a recurrent stroke while on secondary stroke prevention medications, it is vital to assess whether they were taking the medications that they were prescribed and, if possible, to explore and address factors that contributed to nonadherence before assuming that the medications were ineffective. Antithrombotic DosingUnless stated otherwise in the recommendations herein, the international normalized ratio (INR) goal for warfarin is 2.0 to 3.0 and the dose of aspirin is 81 to 325 mg. Application Across PopulationsUnless otherwise indicated, the recommendations in this guideline apply across race/ethnicity, sex, and age groups. Special considerations to address health equity are delineated in section 6.3, Health Equity. DIAGNOSTIC EVALUATION FOR SECONDARY STROKE PREVENTION Recommendations for Diagnostic EvaluationReferenced studies that support recommendations are summarized in online Data Supplements 1 and 2. CORLOE Recommendations 1 B-R Recommendations for Diagnostic Evaluation (Continued) COR LOE Recommendations

LeaderT here is a demand from regulators that new treatments for the management of hyperglycaemia in people with type 2 diabetes should not increase cardio vascular risk. 1,2 For most new therapies this will include the performance of a dedicated randomised-controlled cardiovascular outcomes trial (CVOT). This can be conducted prior to licensing, like the SUSTAIN-6 trial with semaglutide, 3 or post-licensing, like the LEADER trial with liraglutide. 4 The results of CVOTs with albiglutide, a once-weekly GLP-1 receptor agonist, and linagliptin, a DPP-4 inhibitor, were presented at the recent meeting of the European Association for the Study of Diabetes (EASD) in Berlin. 5,6 As there are now several completed trials with GLP-1 receptor agonists and DPP-4 inhibitors it is relevant to place the results of these studies in the context of the results of previous studies. Harmony OutcomesAlbiglutide is a once-weekly GLP-1 receptor agonist composed of two copies of modified human GLP-1 fused to human albumin. It was available for clinical use in the US and Europe from 2014. In the summer of 2017 the manufacturer GlaxoSmithKline announced that albiglutide would be withdrawn from the worldwide market by 2018 for economic reasons that were not detailed, and marketing ceased in July 2018. A lack of potency compared to other GLP-1 receptor agonists, 7 and the inconvenience to the patient of having to reconstitute the lyophilised powder with a diluent and wait 15-30 minutes before injection 8 may have contributed to the low use of albiglutide in countries where other onceweekly GLP-1 receptor agonists were available.Harmony Outcomes was a post-licensing CVOT comparing albiglutide and placebo in 9463 people with type 2 diabetes and established cardiovascular disease, including coronary vascular disease, cerebrovascular disease and peripheral arterial disease. 5 Other inclusion criteria included age over 40 years, and HbA1c over 7.0% (53mmol/mol). At baseline 70% of participants had coronary heart disease, 47% had a previous myocardial infarction and 20% were recorded as having baseline heart failure by their local clinical investigator. Subjects were followed for a median of 1.6 years and the primary outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke.Subjects in the albiglutide arm had a statistically significant 22% reduction in MACE compared to the placebo group. This was despite one-quarter of the subjects discontinuing therapy during this short study. Of the components of the MACE outcome, myocardial infarction (fatal or non-fatal) was significantly reduced, with insignificant effects on stroke and cardiovascular death. The number of subjects needed to treat with albiglutide for 1.6 years to prevent one major adverse cardiovascular event was 50. In the placebo group there was as expected a greater use of sulphonylureas and insulin, including greater use of bolus insulin. Hypoglycaemia rates were lower with albiglutide, including le...

Abstract-The aim of this updated statement is to provide comprehensive and timely evidence-based recommendations on the prevention of ischemic stroke among survivors of ischemic stroke or transient ischemic attack. Evidence-based recommendations are included for the control of risk factors, interventional approaches for atherosclerotic disease, antithrombotic treatments for cardioembolism, and the use of antiplatelet agents for noncardioembolic stroke. Further recommendations are provided for the prevention of recurrent stroke in a variety of other specific circumstances, including arterial dissections; patent foramen ovale; hyperhomocysteinemia; hypercoagulable states; sickle cell disease; cerebral venous sinus thrombosis; stroke among women, particularly with regard to pregnancy and the use of postmenopausal hormones; the use of anticoagulation after cerebral hemorrhage; and special approaches to the implementation of guidelines and their use in high-risk populations. (Stroke. 2011;42:227-276.)

BACKGROUND Patients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease. METHODS In this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction. RESULTS By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P = 0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; P<0.001). There was no significant between-group difference in all-cause mortality (hazard ratio, 0.93; 95% CI, 0.73 to 1.17; P = 0.52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg than was placebo (52.2% vs. 33.7%, P<0.001), edema (35.6% vs. 24.9%, P<0.001), and bone fracture requiring surgery or hospitalization (5.1% vs. 3.2%, P = 0.003). CONCLUSIONS In this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00091949.)