No abstract

This study confirmed the robustness of the association between cryptorchidism and testicular cancer even after adjustment for birth weight and birth order. Furthermore, the study showed an inverse association between birth weight and testicular cancer.

To characterise the cardiovascular risk of people with type 2 diabetes without established cardiovascular disease but with risk factors, relative to those with established cardiovascular disease, to provide information on which patients could benefit from early use of glucose-lowering therapies that also reduce cardiovascular risk.Methods: Data from people with type 2 diabetes initiating second-line glucoselowering medication were retrieved from the UK Clinical Practice Research Datalink GOLD database and linked with Hospital Episode Statistics and Office for National Statistics (2001Statistics ( -2016. Cox proportional hazards models were used to estimate relative risks of major adverse cardiovascular events within groups defined by the presence of selected risk factors in people without versus with established cardiovascular disease.Results: Of 53,182 individuals, 19.4% had established cardiovascular disease (i.e. a prior cardiovascular event). Over 5-7 years' follow-up, the rate of major adverse cardiovascular events was 14.0 and 49.6 events/1000 person-years without and with established cardiovascular disease, respectively (hazard ratio [HR] 0.28, 95% confidence interval [CI] 0.26, 0.29). Compared with a reference HR 1.0 for participants with established cardiovascular disease, estimated glomerular filtration rate <60 mL/min was the single factor associated with the highest risk of major adverse cardiovascular events (HR 0.75, 95% CI 0.70, 0.81) and mortality (HR 1.12, 95% CI 1.07, 1.18) in people with type 2 diabetes without established cardiovascular disease. The combination of chronic kidney disease with older age, smoking and/or dyslipidaemia was associated with a similarly high risk of cardiovascular events in people with type 2 diabetes and without cardiovascular disease compared with those having established cardiovascular disease.

Purpose IDegAsp, a co-formulation of long-acting basal (insulin degludec) and rapid-acting bolus (insulin aspart) insulin, provides separate prandial and basal glucose-lowering effects with relatively low risk of hypoglycaemia. Its efficacy and safety have been investigated in a large clinical trial programme (BOOST). We present the rationale and design of the ARISE study, which aims to assess glycaemic control and other clinical parameters associated with IDegAsp use in real world. Methods ARISE is a ~26-wk-long, prospective, non-interventional, single-arm study of patients with type 2 diabetes (T2D) initiating IDegAsp treatment. Approximately 1112 patients with T2D aged ≥18 years previously on anti-hyperglycaemic drugs except IDegAsp will be enroled across six countries from 15 Aug 2019 to 12 Nov 2020. IDegAsp treatment will be initiated at the physicians’ discretion and as per the local label. Key exclusion criteria include previous participation, or previous IDegAsp treatment. The primary and secondary endpoints are change in HbA1c from baseline (wk 0) to study end (wk 26–36) and the proportion of patients achieving the target HbA1c level of <7% at the study end, respectively. A mixed model for repeated measurements will analyse the primary endpoint. Conclusion Between-country differences in the prescription patterns of glucose-lowering agents in people with T2D warrant examination of their clinical use in different geographical settings. The ARISE study is designed to assess the clinical use of IDegAsp from real world in six different countries. Findings from the ARISE study will supplement those of previous randomised controlled studies by establishing real-world evidence of IDegAsp use in the participating countries. Trial registration ClinicalTrials.gov, NCT04042441. Registered 02 August 2014, https://clinicaltrials.gov/ct2/show/NCT04042441

Randomized controlled trials (RCTs) support use of a glucagon-like peptide-1 receptor agonist (GLP-1RA) combined with a sodium-glucose cotransporter-2 inhibitor (SGLT2i) in people with type 2 diabetes (T2D). As RCTs do not fully reflect the real world, there is a need to explore the real-world population on this combination and determine outcomes with this approach. As a first step, in this large-scale cross-sectional study, we identified adults with T2D, ≥2 prescriptions for GLP-1RA and/or SGLT2i and available data from electronic medical records in the U.S. IBM Explorys database. The first prescription of GLP-1RA and/or SGLT2i in 2018 set the index date, irrespective of prior prescriptions. Data 6 months pre-index were used for patient characteristics and up to 5 years pre-index for medical history. Of 41,421 patients, 12.8% had GLP-1RA+SGLT2i prescribed together, 46.0% GLP-1RA and 41.2% SGLT2i. Of those prescribed both drugs, female: 48.0%; BMI ≥35 kg/m2: 50.2%; mean age: 56.2 years; mean HbA1c 8.3%. In multinomial regression, there was little difference between those prescribed GLP-1RA+SGLT2i vs. either drug alone in terms of HbA1c or presence of comorbidities (data not shown). However, those prescribed both drugs vs. GLP-1RA alone were less likely to be ≥65 years (odds ratio 0.57 [95% CI 0.51;0.63]), have a history of chronic kidney disease (CKD; 0.56 [0.49;0.66]) and more likely to have prior prescription of metformin (1.56 [1.46;1.68]). Those prescribed both drugs vs. SGLT2i alone were less likely to be ≥65 years (0.60 [0.54;0.67]) and have prior prescription of dipeptidyl peptidase-4 inhibitor (0.57 [0.52;0.61]), but more likely to have BMI ≥35 kg/m2 (2.11 [1.75;2.54]) and prior prescription of insulin (1.97 [1.84;2.11]). Those prescribed GLP-1RA+SGLT2i vs. either drug in 2018 had many common characteristics. However, key differentiators (age, obesity, CKD history and prior glucose-lowering drugs) reflected considerations for each therapy based on data available then. Disclosure R.J. McCrimmon: Advisory Panel; Self; Novo Nordisk A/S, Sanofi-Aventis. H.N. Christensen: Employee; Self; AstraZeneca, Novo Nordisk A/S. I. Holst: Employee; Self; Novo Nordisk A/S. A. Lenart: Employee; Self; Novo Nordisk A/S. B. Ludvik: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; Bayer Healthcare Pharmaceuticals Inc., Eli Lilly and Company, Merck & Co., Inc., Novartis Pharmaceuticals Corporation. Speaker’s Bureau; Self; Amgen. R.S. Brandt: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. J.S. Piltoft: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. A. Philis-Tsimikas: Advisory Panel; Self; Lilly Diabetes, Medtronic, Novo Nordisk A/S, Sanofi. Employee; Spouse/Partner; Ionis Pharmaceuticals, Inc. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Dexcom, Inc., Lilly Diabetes, Medtronic, Novo Nordisk A/S, Sanofi. Funding Novo Nordisk A/S