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Objectives: For patients with type 2 diabetes, newer antihyperglycaemic agents (AHA), including the dipeptidyl peptidase IV inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium glucose co-transporter 2 inhibitors (SGLT2i) offer a lower risk of hypoglycaemia relative to sulfonylurea or insulin. However, it is not clear how AHA compare to placebo on risk of any hypoglycaemia. This study evaluates the risk of any and severe hypoglycaemia with AHA and metformin relative to placebo., Design: A systematic review and meta-analysis was conducted of randomized, placebo-controlled trials ≥12 weeks in duration. MEDLINE, Embase and the Cochrane Library were searched up to April 16, 2019. Studies allowing use of other diabetes medications were excluded. Mantel-Haenszel risk ratio with 95% confidence intervals were used to pool estimates based on class of AHA and number of concomitant therapies used., Patients: Eligible studies enrolled patients with type 2 diabetes ≥18 years of age., Results: 144 studies met our inclusion criteria. Any hypoglycaemia was not increased with AHA when used as monotherapy (DPP4i (RR 1.12; 95% CI 0.81-1.56), GLP1RA (1.77; 0.91-3.46), SGLT2i (1.34; 0.83-2.15)), or as add-on to metformin (DPP4i (0.95; 0.67-1.35), GLP1RA (1.24; 0.80-1.91), SGLT2i (1.29; 0.91-1.83)) or as triple therapy (1.13; 0.67-1.91). However, metformin monotherapy (1.73; 1.02-2.94) and dual therapy initiation (3.56; 1.79-7.10) was associated with an increased risk of any hypoglycaemia. Severe hypoglycaemia was rare not increased for any comparisons., Conclusions: Metformin and the simultaneous initiation of dual therapy, but not AHA used alone or as single add-on combination therapy, was associated with an increased risk of any hypoglycaemia relative to placebo., Competing Interests: Ms Kamalinia initiated her Master's degree while an employee of Merck Canada Inc. with educational support but has since left to focus on her studies. Merck Canada Inc did not play any role in the conception of the research question, protocol development, data synthesis or interpretation. Dr RGJ reports personal fees from Merck, AZ, Novo Nordisk, Lilly/BI and Janssen, outside the submitted work. Ms LL, Mr PJD and Dr BRS declare no competing interests. Dr SWT reports grants from Eli Lilly, Astra Zeneca, AbbVie and Bayer for participation in international contract research studies as well as honoraria for speaker's bureaus from Servier and Valeant during the conduct of the study and has had travel reimbursed by the Novartis Foundation., (© 2019 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Background: Geographic factors may influence cardiovascular disease outcomes in Canada. Circulatory diseases are a major reason for higher population mortality rates in Northern Ontario, but it is unknown if hospitalized patients with cardiovascular disease experience differential outcomes compared with those in the South., Methods: We examined 30-day and 1-year mortality and readmissions for patients hospitalized with acute myocardial infarction (AMI), heart failure (HF), atrial fibrillation (AF), or stroke in Northern compared with Southern Ontario, using the Canadian Institute for Health Information Discharge Abstract Database (2005-2016). Northern patients were defined as those residing and hospitalized in the Northwest or Northeast Local Health Integration Network regions. We used multiple Cox proportional hazards regression analysis for time-to-first event and Prentice-Williams-Peterson method to evaluate repeat and multiply admitted patients., Results: A total of 47,745 Northern and 465,353 Southern patients hospitalized with AMI (n = 182,158), HF (n = 130,770), AF (n = 72,326), or stroke (n = 127,844) were studied. Rates of first readmission were higher among Northern patients for AMI (adjusted hazard ratio [HR], 1.32), HF (HR, 1.16), AF (HR, 1.21), and stroke (HR, 1.27) compared with Southern patients (all P < 0.001). Repeat readmission rates among Northern patients for AMI (HR, 1.23), HF (HR, 1.13), AF (HR, 1.18), and stroke (HR, 1.22) were also increased (all P < 0.001 vs Southern). Thirty-day mortality did not differ significantly between Northern and Southern patients., Conclusions: Readmissions were increased in those residing and hospitalized in the North. To reduce readmissions in the North, the quality of postacute transitional care should be examined further., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)