Self-Reported Frequency and Impact of Hypoglycemic Events in Spain

INTRODUCTION: Hypoglycemia is a common side effect of insulin therapy and has negative implications for quality of life and healthcare resources. The authors investigated the self-reported frequency of non-severe and severe hypoglycemic events (NSHEs and SHEs), hypoglycemia awareness, patient–physician communication, health-related effects and economic impact on people with insulin-treated diabetes (Type-1 and Type-2) in Spain. METHODS: People with Type-1 (T1DM) or insulin-treated Type-2 (T2DM) diabetes older than 15 years of age completed up to 4 questionnaires at weekly intervals. NSHE was an event which respondents could manage without assistance. SHE needed help from a third party to manage. RESULTS: In total, 630 respondents completed questionnaires covering 2,235 weeks. Mean self-reported NSHEs per respondent-week were 1.7 (T1DM) and 0.4–0.8 (T2DM). Impaired hypoglycemia awareness or unawareness was reported by 55% of T1DM and 39% of T2DM respondents. Overall, 31% of T1DM and 20% of T2DM respondents rarely/never informed their physician about NSHEs. Respondents reported feeling tired/fatigued after 67% of NSHE and less alert after 45% of NSHE. Over the week following an NSHE, blood glucose measurement test-strip use increased by 5.3 (mean). In employed respondents (43%), 18% of NSHEs were reported to lead to lost work time (mean 1.5 h per event). After an SHE, 49% of respondents required emergency visits and/or hospital admission. CONCLUSION: NSHE are a common occurrence with T1DM and insulin-treated T2DM in Spain and are associated with a cost burden and negative impact on well-being. Patient–physician communication is higher in Spain than Europe overall; however, many patients expressed reluctance to discuss their hypoglycemia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13300-014-0057-z) contains supplementary material, which is available to authorized users

Cost-effectiveness analysis of insulin degludec compared with insulin glargine u100 for the management of type 1 and type 2 diabetes mellitus - from the Spanish National Health System perspective

The objective of this study was to assess the cost-effectiveness of insulin degludec versus insulin glargine, from the Spanish NHS in three groups of patients. Methods: A short-term cost utility model was developed to estimate effectiveness results in terms of the total number of hypoglycaemic events and their disutility impact throughout the year on the initial level of quality of life for patients in each treatment

Clinical Effects of Liraglutide in a Real-World Setting in Spain: eDiabetes-Monitor SEEN Diabetes Mellitus Working Group Study

Introduction: A limitation with randomized controlled trials is that, while they provide unbiased evidence of the efficacy of interventions, they do so under unreal conditions and in a very limited and highly selected patient population. Our aim was to provide data about the effectiveness of liraglutide treatment in a real-world and clinical practice setting. Methods: In a retrospective and observational study, data from 753 patients with type 2 diabetes were recorded through an online tool (eDiabetes-Monitor). Results: Mean baseline glycated hemoglobin (HbA1c) was 8.4 ± 1.4% and mean body mass index (BMI) was 38.6 ± 5.4 kg/m2. After 3–6 months of treatment with liraglutide, we observed a change in HbA1c of -1.1 ± 1.2%, -4.6 ± 5.3 kg in weight and -1.7 ± 2.0 kg/m

Clinical Recommendations to Manage Gastrointestinal Adverse Events in Patients Treated with Glp-1 Receptor Agonists: A Multidisciplinary Expert Consensus

Gastrointestinal adverse events; Obesity; Type 2 diabetesEsdeveniments adversos gastrointestinals; Obesitat; Diabetis tipus 2Eventos adversos gastrointestinales; Obesidad; Diabetes tipo 2Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are indicated in type 2 diabetes and obesity for their high efficacy in controlling glycaemia and inducing body weight loss, respectively. Patients may develop gastrointestinal adverse events (GI AEs), namely nausea, vomiting, diarrhoea and/or constipation. To minimize their severity and duration, healthcare providers (HCPs) and patients must be aware of appropriate measures to follow while undergoing treatment. An expert panel comprising endocrinologists, nephrologists, primary care physicians, cardiologists, internists and diabetes nurse educators convened across virtual meetings to reach a consensus regarding these compelling recommendations. Firstly, specific guidelines are provided about how to reach the maintenance dose and how to proceed if GI AEs develop during dose-escalation. Secondly, specific directions are set about how to avoid/minimize nausea, vomiting, diarrhoea and constipation symptoms. Clinical scenarios representing common situations in daily practice, and infographics useful to guide both HCPs and patients, are included. These recommendations may prevent people with T2D and/or obesity from withdrawing from GLP-1 RAs treatment, thus benefitting from their superior effect on glycaemic control and weight loss.This work has been funded by Novo-Nordisk

Comprehensive approach to people with type 2 diabetes. Diabetes Knowledge Area of the Spanish Society of Endocrinology and Nutrition

[ES] Objetivo: Proporcionar recomendaciones prácticas para el abordaje integral de las personas con diabetes tipo 2 según la medicina basada en la evidencia. Participantes: Miembros del Área de Conocimiento de Diabetes de la Sociedad Española de Endocrinología y Nutrición. Métodos: Las recomendaciones se formularon según los grados de evidencia de los Standards of Medical Care in Diabetes—2022. Tras la revisión de la evidencia disponible y la formulación de recomendaciones por los autores de cada apartado, se desarrollaron varias rondas de comentarios con incorporación de las aportaciones y votación de los puntos controvertidos. Por último, el documento final se remitió al resto de los miembros del área para revisión e incorporación de aportaciones, para, finalmente, realizar el mismo proceso con los miembros de la Junta Directiva de la Sociedad Española de Endocrinología y Nutrición. Conclusiones: El documento establece unas recomendaciones prácticas basadas en la última evidencia disponible para el manejo de las personas con diabetes tipo 2.[EN] Objective. To provide practical recommendations for the comprehensive approach of people with type 2 diabetes according to evidence-based medicine. Participants. Members of the Diabetes Knowledge Area of the Spanish Society of Endocrinology and Nutrition. Methods. The recommendations were formulated according to the degrees of evidence of the Standards of Medical Care in Diabetes—2022. After reviewing the available evidence and formulating recommendations by the authors of each section, several rounds of comments were developed incorporating the contributions and voting on controversial points. Finally, the final document was sent to the rest of the members of the area for review and incorporation of contributions, to finally carry out the same process with the members of the Spanish Society of Endocrinology and Nutrition Board of Directors. Conclusions. The document establishes practical recommendations based on the latest available evidence for the management of people with type 2 diabetes.Peer reviewe

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

Background: Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods: In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings: The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p<0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than placebo at week 160 (–6·1 [SD 7·3] vs −1·9% [6·3]; estimated treatment difference −4·3%, 95% CI −4·9 to −3·7, p<0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation: In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding: Novo Nordisk, Denmark

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor 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. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Benefits of SGLT2i for the Treatment of Heart Failure Irrespective of Diabetes Diagnosis: A State-of-the-Art Review.

Morbidity and mortality associated with heart failure (HF) has remained high despite advances in therapy. Furthermore, HF-associated risk in patients with type 2 diabetes mellitus (T2D) is even higher than in patients without T2D owing to the strong reciprocal relationship between conditions. However, until recently, no therapy to treat patients with diabetes also reduced cardiovascular risks related to HF. Recent clinical studies (DAPA-HF, EMPEROR-Reduced and EMPEROR-Preserved, SOLOIST-WHF trial) and meta-analysis have demonstrated that sodium-glucose cotransporter-2 inhibitors (SGLT2i) are among the first antidiabetic drugs capable of reducing cardiovascular risks related to HF and improving the prognosis of patients with and without diabetes. Their pleiotropic mechanisms of action place them at the intersection of hemodynamic, metabolic, and neurohumoral pathways, with clear advantages for treating these patients independent of its glucose-lowering effect. Moreover, the benefits of SGLT2i were consistent across the cardiorenal continuum in different populations and clinical settings, which has led to different guidelines introducing SGLT2i as a first-line treatment for HF

Cost-effectiveness analysis of insulin degludec compared with insulin glargine u100 for the management of type 1 and type 2 diabetes mellitus - from the Spanish National Health System perspective

The objective of this study was to assess the cost-effectiveness of insulin degludec versus insulin glargine, from the Spanish NHS in three groups of patients. Methods: A short-term cost utility model was developed to estimate effectiveness results in terms of the total number of hypoglycaemic events and their disutility impact throughout the year on the initial level of quality of life for patients in each treatment

Calcifediol in the management of vitamin D deficiency-related skeletal and extraskeletal diseases: overview and clinical cases

As well as being essential for musculoskeletal health, vitamin D is involved in numerous other physiological processes. Poor vitamin D status is linked to a wide range of diseases, including cardiovascular disease, autoimmune conditions, pulmonary disorders and upper respiratory tract infections. While optimal target concentrations of serum 25-hydroxyvitamin D (25(OH)D) for health maintenance or therapeutic purposes are still the subject of debate, there is reasonable agreement that serum 25(OH)D levels <50 nmol/L (20 ng/mL) constitute vitamin D deficiency and that severe deficiency states (serum 25(OH)D levels <25-30 nmol/L ≈ 10-12 ng/ mL) should be avoided. Main strategies to maintain or improve vitamin D status are food supplementation and therapeutic use of medicinal forms of vitamin D. In this review, we examine evidence that implicates vitamin D deficiency in diverse conditions in the clinical settings of endocrinology, rheumatology, pneumology and reproductive health. Cholecalciferol (vitamin D3) is the most frequently used vitamin D supplement worldwide, though calcifediol (25-hydroxyvitamin D3) has recently become more widely available. Calcifediol is one step closer than cholecalciferol in the metabolic pathway to biologically active vitamin D. Pharmacokinetic differences between these vitamin D metabolites confer putative advantages for calcifediol in certain clinical situations. The clinical use of calcifediol is explored more closely through case studies, which illustrate its adjunctive role in the treatment of several vitamin D deficiency-related skeletal and extraskeletal diseases