No abstract

No abstract

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.

No abstract

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 In the summer of 2017 the manufacturer GlaxoSmithKline announced that albiglutide would be withdrawn from the worldwide market by 2018 for economic reasons that were not detailed, and marketing ceased in July 2018.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...

Background: Glucagon-like peptide 1 agonists differ in chemical structure, duration of action and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. Methods: We randomly assigned patients with type 2 diabetes and cardiovascular disease to the addition of once-weekly subcutaneous injection of albiglutide (30 mg to 50 mg) or matching placebo to standard care. We hypothesized that albiglutide would be noninferior to placebo for the primary outcome of first occurrence of cardiovascular death, myocardial infarction, or stroke. If noninferiority was confirmed by an upper limit of the 95% confidence interval for the hazard ratio of less than 1.30, closed-testing for superiority was prespecified. Findings: Overall, 9463 participants were followed for a median of 1.6 years. The primary composite outcome occurred in 338 of 4731 patients (7.1%; 4.6 events per 100 person-years) in the albiglutide group and in 428 of 4732 patients (9.0%; 5.9 events per 100 person-years) in the placebo group (hazard ratio, 0.78; 95% confidence interval [CI ], 0.68 to 0.90), indicating that albiglutide, was superior to placebo (P<0.0001 for noninferiority, P=0.0006 for superiority). The incidence of acute pancreatitis (albiglutide 10 patients and placebo 7 patients), pancreatic cancer (6 and 5), medullary thyroid carcinoma (0 and 0), and other serious adverse events did not differ significantly between the two groups. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. (Funded by GlaxoSmithKline; Harmony Outcomes ClinicalTrials.gov number, NCT02465515.) noninferiority; P = 0.06 for superiority). There seems to be variation in the results of existing trials with GLP-1 receptor agonists, which if correct, might reflect drug structure or duration of action, patients studied, duration of follow-up or other factors.

The American Diabetes Association and the European Association for the Study of Diabetes have briefly updated their 2018 recommendations on management of hyperglycemia, based on important research findings from large cardiovascular outcomes trials published in 2019. Important changes include: 1) the decision to treat high-risk individuals with a glucagon-like peptide 1 (GLP-1) receptor agonist or sodium-glucose cotransporter 2 (SGLT2) inhibitor to reduce major adverse cardiovascular events (MACE), hospitalization for heart failure (hHF), cardiovascular death, or chronic kidney disease (CKD) progression should be considered independently of baseline HbA 1c or individualized HbA 1c target; 2) GLP-1 receptor agonists can also be considered in patients with type 2 diabetes without established cardiovascular disease (CVD) but with the presence of specific indicators of high risk; and 3) SGLT2 inhibitors are recommended in patients with type 2 diabetes and heart failure, particularly those with heart failure with reduced ejection fraction, to reduce hHF, MACE, and CVD death, as well as in patients with type 2 diabetes with CKD (estimated glomerular filtration rate 30 to £60 mL min-1 [1.73 m]-2 or urinary albumin-to-creatinine ratio >30 mg/g, particularly >300 mg/g) to prevent the progression of CKD, hHF, MACE, and cardiovascular death. The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) requested a brief update of the 2018 recommendations on management of hyperglycemia (1,2), based on the important research findings published in 2019, with a particular focus on new data from large cardiovascular outcomes trials (CVOTs). The authors began work on the brief update in July 2019 and submitted it for publication in Diabetes Care and Diabetologia in October 2019. Work was conducted over a series of phone calls and by electronic interactions. This brief update provides a summary of the implications of this new evidence on recommendations for the management of hyperglycemia in type 2 diabetes (see text box), which will be addressed more fully in the ADA Standards of Medical Care in Diabetesd2020 (https://professional.diabetes.org/ SOC). It should be considered in conjunction with the 2018 consensus report (1,2). The Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial of the glucagon-like peptide 1 (GLP-1) receptor agonist dulaglutide

No abstract