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.

AimsTherapeutic inertia, defined as the failure to initiate or intensify therapy in a timely manner according to evidence‐based clinical guidelines, is a key reason for uncontrolled hyperglycaemia in patients with type 2 diabetes. The aims of this systematic review were to identify how therapeutic inertia in the management of hyperglycaemia was measured and to assess its extent over the past decade.Materials and MethodsSystematic searches for articles published from January 1, 2004 to August 1, 2016 were conducted in MEDLINE and Embase. Two researchers independently screened all of the titles and abstracts, and the full texts of publications deemed relevant. Data were extracted by a single researcher using a standardized data extraction form.ResultsThe final selection for the review included 53 articles. Measurements used to assess therapeutic inertia varied across studies, making comparisons difficult. Data from low‐ to middle‐income countries were scarce. In most studies, the median time to treatment intensification after a glycated haemoglobin (HbA1c) measurement above target was more than 1 year (range 0.3 to >7.2 years). Therapeutic inertia increased as the number of antidiabetic drugs rose and decreased with increasing HbA1c levels. Data were mainly available from Western countries. Diversity of inertia measures precluded meta‐analysis.ConclusionsTherapeutic inertia in the management of hyperglycaemia in patients with type 2 diabetes is a major concern. This is well documented in Western countries, but corresponding data are urgently needed in low‐ and middle‐income countries, in view of their high prevalence of type 2 diabetes.

BackgroundThe global prevalence of type 2 diabetes-related complications is not well described. We assessed prevalence of vascular complications at baseline in DISCOVER (NCT02322762; NCT02226822), a global, prospective, observational study program of 15,992 patients with type 2 diabetes initiating second-line therapy, conducted across 38 countries.MethodsPatients were recruited from primary and specialist healthcare settings. Data were collected using a standardized case report form. Prevalence estimates of microvascular and macrovascular complications at baseline were assessed overall and by country and region, and were standardized for age and sex. Modified Poisson regression was used to assess factors associated with the prevalence of complications.ResultsThe median duration of type 2 diabetes was 4.1 years (interquartile range [IQR]: 1.9–7.9 years), and the median glycated hemoglobin (HbA1c) level was 8.0% (IQR: 7.2–9.1%). The crude prevalences of microvascular and macrovascular complications were 18.8% and 12.7%, respectively. Common microvascular complications were peripheral neuropathy (7.7%), chronic kidney disease (5.0%), and albuminuria (4.3%). Common macrovascular complications were coronary artery disease (8.2%), heart failure (3.3%) and stroke (2.2%). The age- and sex-standardized prevalence of microvascular complications was 17.9% (95% confidence interval [CI] 17.3–18.6%), ranging from 14.2% in the Americas to 20.4% in Europe. The age- and sex-standardized prevalence of macrovascular complications was 9.2% (95% CI 8.7–9.7%), ranging from 4.1% in South-East Asia to 18.8% in Europe. Factors positively associated with vascular complications included age (per 10-year increment), male sex, diabetes duration (per 1-year increment), and history of hypoglycemia, with rate ratios (95% CIs) for microvascular complications of 1.14 (1.09–1.19), 1.30 (1.20–1.42), 1.03 (1.02–1.04) and 1.45 (1.25–1.69), respectively, and for macrovascular complications of 1.41 (1.34–1.48), 1.29 (1.16–1.45), 1.02 (1.01–1.02) and 1.24 (1.04–1.48), respectively. HbA1c levels (per 1.0% increment) were positively associated with microvascular (1.05 [1.02–1.08]) but not macrovascular (1.00 [0.97–1.04]) complications.ConclusionsThe global burden of microvascular and macrovascular complications is substantial in these patients with type 2 diabetes who are relatively early in the disease process. These findings highlight an opportunity for aggressive early risk factor modification, particularly in regions with a high prevalence of complications.Trial registration ClinicalTrials.gov; NCT02322762. Registered 23 December 2014. https://clinicaltrials.gov/ct2/show/NCT02322762. ClinicalTrials.gov; NCT02226822. Registered 27 August 2014. https://clinicaltrials.gov/ct2/show/NCT02226822Electronic supplementary materialThe online version of this article (10.1186/s12933-018-0787-8) contains supplementary material, which is available to authorized users.

Arterial hypertension in adults. Clinical guidelines 2020

Dear Colleagues! We are glad to present the8th Editionof Standards of Diabetes Care. These evidence-based guidelines were designed to standardize and facilitate diabetes care in all regions of the Russian Federation. The Standards are updated on the regular basis to incorporate new data and relevant recommendations from national and international clinical societies, including World Health Organization Guidelines (WHO, 2011, 2013), International Diabetes Federation (IDF, 2011, 2012, 2013), American Diabetes Association (ADA, 2012, 2017), American Association of Clinical Endocrinologists (AACE, 2017), International Society for Pediatric and Adolescent Diabetes (ISPAD, 2014) and Russian Association of Endocrinologists (RAE, 2011, 2012, 2015). Current edition of the Standards also integrates results of completed randomized clinical trials (ADVANCE, ACCORD, VADT, UKPDS, SAVOR, TECOS, LEADER, EMPA-REG OUTCOME, etc.), as well as findings from the national studies of diabetes mellitus (DM), conducted in close partnership with a number of Russian hospitals. Latest data indicates that prevalence of DM in the world increased during the last decade more than two-fold, reaching some 415 million patients by the end of 2015. According to the current estimation by the International Diabetes Federation, 642 million patients will be suffering from DM by 2040. These observations resulted in the UN Resolution on Diabetes 61/225 passed on 20.12.2006, and in 2011 - UN Political Declaration, addressed to national health systems, calling for the establishment of multidisciplinary strategy in the prevention and control of non-communicable diseases, where special attention is drawn to the problem of diabetes as one of the leading causes of disability and mortality. Like many other countries, Russian Federation experiences a sharp rise in the prevalence of DM. According to Russian Federal Diabetes Register, there are at least 4.35 million patients with DM in this country by the end of 2016 (3% of population) with 92% (4 million) Type 2 DM, 6% (255 th) Type 1 DM and 2% (75 th) other types of DM. However, these results underestimates real quantity of patients, because they consider only registered cases. Results of Russian epidemiological study (NATION) confirmed that only 50% of Type 2 DM are diagnosed. So real prevalence of patients with DM in Russia is no less than 8-9 million patients (about 6% of population). This is a great long-term problem, because a lot of patients are not diagnosed, so they dont receive any treatment ant have high risk of vascular complications. Severe consequences of the global pandemics of DM include its vascular complications: nephropathy, retinopathy, coronary, cerebral, coronary and peripheral vascular disease. These conditions are responsible for the majority of cases of diabetes-related disability and death. Current edition of the Standards emphasizes the patient-oriented approach in making decisions on therapeutic goals, such as levels of glycaemia and blood pressure. It also features updated guidelines on the management of Type 2 DM and its vascular complications, added information about bariatric surgery as a method of treatment of DM with morbide obesity. This text represents a consensus by the absolute majority of national experts, achieved through a number of fruitful discussions held at national meetings and forums. These guidelines are intended for endocrinologists and diabetologists, primary care physicians, cardiologists and other medical professionals involved in prevention and treatment of DM. On behalf of the Working Group

Dear Colleagues! We are glad to present the 9th Edition (revised) of Standards of Diabetes Care. These evidence-based guidelines were designed to standardize and facilitate diabetes care in all regions of the Russian Federation. The Standards are updated on the regular basis to incorporate new data and relevant recommendations from national and international clinical societies, including World Health Organization Guidelines (WHO, 2011, 2013), International Diabetes Federation (IDF, 2011, 2012, 2013), American Diabetes Association (ADA, 2018, 2019), American Association of Clinical Endocrinologists (AACE, 2019), International Society for Pediatric and Adolescent Diabetes (ISPAD, 2014, 2018) and Russian Association of Endocrinologists (RAE, 2011, 2012, 2015). Current edition of the Standards also integrates results of completed randomized clinical trials (ADVANCE, ACCORD, VADT, UKPDS, SAVOR, TECOS, LEADER, EXAMINE, ELIXA, SUSTAIN, DEVOTE, EMPA-REG OUTCOME, CANVAS, DECLARE, CARMELINA, REWIND, etc.), as well as findings from the national studies of diabetes mellitus (DM), conducted in close partnership with a number of Russian hospitals. Latest data indicates that prevalence of DM in the world increased during the last decade more than two-fold, reaching some 463 million patients by the end of 2019. According to the current estimation by the International Diabetes Federation, 578 million patients will be suffering from diabetes mellitus by by 2030 and 700 million by 2045. Like many other countries, Russian Federation experiences a sharp rise in the prevalence of DM. According to Russian Federal Diabetes Register, there are at least 4 584 575 patients with DM in this country by the end of 2018 (3,1% of population) with 92% (4 238 503) Type 2 DM, 6% (256 202) Type 1 DM and 2% (89 870) other types of DM, including 8 006 women with gestational DM. However, these results underestimates real quantity of patients, because they consider only registered cases. Results of Russian epidemiological study (NATION) con- firmed that only 54% of Type 2 DM are diagnosed. So real number of patients with DM in Russia is 9 million patients (about 6% of population). This is a great long-term problem, because a lot of patients are not diagnosed, so they dont receive any treatment ant have high risk of vascular complications. Severe consequences of the global pandemics of DM include its vascular complications: nephropathy, retinopathy, coronary, cerebral, coronary and peripheral vascular disease. These conditions are responsible for the majority of cases of diabetes-related disability and death. In сurrent edition of the Standards: New goals of glycemic control for the elderly, based on the presence of functional dependence, as well as for pregnant women, children and adolescents, are given. Added a snippet that describes the continuous glucose monitoring. Only low-density lipoprotein cholesterol level is used as a target for lipid metabolism. Proposes more stringent target levels of blood pressure. It also features updated guidelines on stratification of treatment in newly diagnosed Type 2 diabetes: the excess of the initial level of HbA1c over the target level was used as a criterion. In the recommendations for the personalization of the choice of antidiabetic agents, it is taken into account that in certain clinical situations (the presence of atherosclerotic cardiovascular diseases and their risk factors, chronic heart failure, chronic kidney disease, obesity, the risk of hypoglycemia) certain classes of hypoglycemic agents (or individual drugs) have proven advantages. Recommendations for psychosocial support are added. The position of metabolic surgery as a method of treatment of DM with morbid obesity is updated. Recommendations for diagnostic and treatment of hypogonadism syndrome in men with DM are added. For the first time, evidence levels of confidence and credibility levels of recommendations for diagnostic, therapeutic, rehabilitative and preventive interventions based on a systematic review of the literature are given in accordance with the recommendations of the Center for Healthcare Quality Assessment and Control of the Ministry of Health of the Russian Federation. This text represents a consensus by the absolute majority of national experts, achieved through a number of fruitful discus- sions held at national meetings and forums. These guidelines are intended for endocrinologists, primary care physicians and other medical professionals involved in the treatment of DM. On behalf of the Working Group

To describe the characteristics and treatment of patients with type 2 diabetes mellitus initiating a second-line glucose-lowering therapy in the global DISCOVER study programme. Methods: DISCOVER comprises two similar 3-year prospective observational studies (NCT02322762 and NCT02226822), involving 15,992 patients initiating a second-line glucose-lowering therapy in 38 countries across six regions (Africa,

Aims/hypothesis We evaluated the secular trend of glycaemic control in individuals with type 2 diabetes in developing countries, where data are limited. Methods The International Diabetes Management Practices Study provides real-world evidence of patient profiles and diabetes care practices in developing countries in seven cross-sectional waves (2005-2017). At each wave, each physician collected data from ten consecutive participants with type 2 diabetes during a 2 week period. The primary objective of this analysis was to evaluate trends of glycaemic control over time. Results A total of 66,088 individuals with type 2 diabetes were recruited by 6099 physicians from 49 countries. The proportion of participants with HbA 1c <53 mmol/mol (<7%) decreased from 36% in wave 1 (2005) to 30.1% in wave 7 (2017) (p < 0.0001). Compared with wave 1, the adjusted ORs of attaining HbA 1c ≤64 mmol/mol (≤8%) decreased significantly in waves 2, 5, 6 and 7 (p < 0.05). Over 80% of participants received oral glucose-lowering drugs, with declining use of sulfonylureas. Insulin use increased from 32.8% (wave 1) to 41.2% (wave 7) (p < 0.0001). The corresponding time to insulin initiation (mean ± SD) changed from 8.4 ± 6.9 in wave 1 to 8.3 ± 6.6 years in wave 7, while daily insulin dosage ranged from 0.39 ± 0.21 U/kg (wave 1) to 0.33 ± 0.19 U/kg (wave 7) for basal regimen and 0.70 ± 0.34 U/kg (wave 1) to 0.77 ± 0.33 (wave 7) U/kg for basal-bolus regimen. An increasing proportion of participants had ≥2 HbA 1c measurements within 12 months of enrolment (from 61.8% to 92.9%), and the proportion of participants receiving diabetes education (mainly delivered by physicians) also increased from 59.0% to 78.3%. Conclusions In developing countries, glycaemic control in individuals with type 2 diabetes remained suboptimal over a 12 year period, indicating a need for system changes and better organisation of care to improve self-management and attainment of treatment goals.