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Objective: Standardised person‐reported outcomes (PRO) data can contextualise clinical outcomes enabling precision diabetes monitoring and care. Comprehensive outcome sets can guide this process, but their implementation in routine diabetes care has remained challenging and unsuccessful at international level. We aimed to address this by developing a person‐centred outcome set for Type 1 and Type 2 diabetes, using a methodology with prospects for increased implementability and sustainability in international health settings. Methods: We used a three‐round questionnaire‐based Delphi study to reach consensus on the outcome set. We invited key stakeholders from 19 countries via purposive snowball sampling, namely people with diabetes (N = 94), healthcare professionals (N = 65), industry (N = 22) and health authorities (N = 3), to vote on the relevance and measurement frequency of 64 previously identified clinical and person‐reported outcomes. Subsequent consensus meetings concluded the study. Results: The list of preliminary outcomes was shortlisted via the consensus process to 46 outcomes (27 clinical outcomes and 19 PROs). Two main collection times were recommended: (1) linked to a medical visit (e.g. diabetes‐specific well‐being, symptoms and psychological health) and (2) annually (e.g. clinical data, general well‐being and diabetes self management‐related outcomes). Conclusions: PROs are often considered in a non‐standardised way in routine diabetes care. We propose a person‐centred outcome set for diabetes, specifically considering psychosocial and behavioural aspects, which was agreed by four international key stakeholder groups. It guides standardised collection of meaningful outcomes at scale, supporting individual and population level healthcare decision making. It will be implemented and tested in Europe as part of the H2O project. [ABSTRACT FROM AUTHOR]

Objective: Patients with diabetes or familial hypercholesterolemia (FH) have an increased incidence of cardiovascular diseases compared with the population, but whether this risk is exacerbated in patients with combined traits is unknown.Research Design and Methods: In this Swedish nationwide, register-based cohort study, patients with diabetes were included between 2002 and 2020. Adjusted Cox proportional hazards models were used to assess the risk of cardiovascular events in patients with or without phenotypic FH (≥6 points for phenotypic FH according to Dutch Lipid Clinic Network criteria) compared with general population control subjects without diabetes as reference.Results: A total of 45,585 patients with type 1 diabetes (227,923 control subjects) and 655,250 patients with type 2 diabetes (655,250 control subjects) were followed for a median of 14.1 and 7.9 years, respectively. Of those, 153 and 7,197, respectively, had phenotypic FH. Compared with control subjects, patients with diabetes and phenotypic FH had higher risk of cardiovascular mortality (type 1: hazard ratio 21.3 [95% CI 14.6-31.0]; type 2: 2.40 [2.19-2.63]) and of a cardiovascular event (type 1: 15.1 [11.1-20.5]; type 2: 2.73 [2.58-2.89]). Further, patients with diabetes and phenotypic FH had higher LDL-cholesterol levels during observation (P < 0.05) and increased risk of all major cardiovascular outcomes (P < 0.0001) than patients with diabetes but without FH. The proportion receiving lipid-lowering treatment was higher in patients with phenotypic FH (P < 0.0001).Conclusions: Patients with both diabetes and phenotypic FH are more at risk for adverse cardiovascular outcomes and have higher LDL-cholesterol levels despite receiving intensified lipid-lowering therapy. [ABSTRACT FROM AUTHOR]

Objective: Type 1 diabetes (T1D) and type 2 diabetes (T2D) increase risks of cardiovascular (CV) and renal disease (CVRD) compared with diabetes-free populations. Direct comparisons between T1D and T2D are scarce. We examined this by pooling full-population cohorts in Sweden and Norway.Research Design and Methods: A total of 59,331 patients with T1D and 484,241 patients with T2D, aged 18-84 years, were followed over a mean period of 2.6 years from 31 December 2013. Patients were identified in nationwide prescribed drug and hospital registries in Norway and Sweden. Prevalence and event rates of myocardial infarction (MI), heart failure (HF), stroke, chronic kidney disease (CKD), all-cause death, and CV death were assessed following age stratification in 5-year intervals. Cox regression analyses were used to estimate risk.Results: The prevalence of CV disease was similar in T1D and T2D across age strata, whereas CKD was more common in T1D. Age-adjusted event rates comparing T1D versus T2D showed that HF risk was increased between ages 65 and 79 years, MI between 55 and 79 years, and stroke between 40 and 54 years (1.3-1.4-fold, 1.3-1.8-fold, and 1.4-1.7-fold, respectively). CKD risk was 1.4-3.0-fold higher in T1D at all ages. The all-cause death risk was 1.2-1.5-fold higher in T1D at age >50 years, with a similar trend for CV death.Conclusions: Adult patients with T1D compared with those with T2D had an overall greater risk of cardiorenal disease (HF and CKD) across ages, MI and all-cause death at middle-older ages, and stroke at younger ages. The total age-adjusted CVRD burden and risks were greater among patients with T1D compared with those with T2D, highlighting their need for improved prevention strategies. [ABSTRACT FROM AUTHOR]

Aims: To investigate how the cardiovascular (CV) risk benefits of dapagliflozin translate into healthcare costs compared with other non‐sodium–glucose cotransporter‐2 inhibitor glucose‐lowering drugs (oGLDs) in a real‐world population with type 2 diabetes (T2D) that is similar to the population of the DECLARE‐TIMI 58 trial. Methods: Patients initiating dapagliflozin or oGLDs between 2013 and 2016 in Swedish nationwide healthcare registries were included if they fulfilled inclusion and exclusion criteria of the DECLARE‐TIMI 58 trial (DECLARE‐like population). Propensity scores for the likelihood of dapagliflozin initiation were calculated, followed by 1:3 matching with initiators of oGLDs. Per‐patient cumulative costs for hospital healthcare (in‐ and outpatient) and for drugs were calculated from new initiation until end of follow‐up. Results: A total of 24 828 patients initiated a new GLD; 6207 initiated dapagliflozin and 18 621 initiated an oGLD. After matching based on 96 clinical and healthcare cost variables, groups were balanced at baseline. Mean cumulative 30‐month healthcare cost per patient was similar in the dapagliflozin and oGLD groups ($11 807 and $11 906, respectively; difference, −$99; 95% CI, −$629, $483; P = 0.644). Initiation of dapagliflozin rather than an oGLD was associated with significantly lower hospital costs (−$658; 95% CI, −$1169, −$108; P = 0.024) and significantly higher drug costs ($559; 95% CI, $471, $648; P < 0.001). Hospital cost difference was related mainly to fewer CV‐ and T2D‐associated complications with use of dapagliflozin compared with use of an oGLD (−$363; 95% CI, −$665, −$61; P = 0.008). Conclusion: In a nationwide, real‐world, DECLARE‐like population, dapagliflozin was associated with lower hospital costs compared with an oGLD, mainly as a result of reduced rates of CV‐ and T2D‐associated complications. [ABSTRACT FROM AUTHOR]

Objectives: Hyperglycemia is a predictor for poor stroke outcome. Hyperglycemic stroke patients treated with thrombolysis have an increased risk of intracranial hemorrhage. Insulin is the gold standard for treating hyperglycemia but comes with a risk of hypoglycemia. Glucagon‐like peptide‐1 receptor agonists (GLP‐1RA) are drugs used in type 2 diabetes that have a low risk of hypoglycemia and have been shown to exert neuroprotective effects. The primary objective was to determine whether prehospital administration of the GLP‐1RA exenatide could lower plasma glucose in stroke patients. Secondary objective was to study tolerability and safety. Materials & Methods: Randomized controlled trial comparing exenatide administrated prehospitally with a control group receiving standard care for hyperglycemia. Patients with Face Arm Speech Test ≥1 and glucose ≥8 mmol/L were randomized. Glucose was monitored for 24 hours. All adverse events were recorded. Results: Nineteen patients were randomized, eight received exenatide. An interim recruitment failure analysis with subsequent changes of the protocol was made. The study was stopped prematurely due to slow inclusion. No difference was observed in the main outcome of plasma glucose at 4 hours, control vs exenatide (mean, SD); 7.0 ± 1.9 vs 7.6 ± 1.6; P = .56). No major adverse events were reported. Conclusions: We found no evidence that prehospital exenatide had effect on hyperglycemia. However, it was given without adverse events in this study with limited sample size that was prematurely stopped due to slow inclusion. [ABSTRACT FROM AUTHOR]

Aims: To investigate cardiovascular (CV) safety and event rates for dapagliflozin versus other glucose‐lowering drugs (GLDs) in a real‐world type 2 diabetes population after applying the main inclusion criteria and outcomes from the DECLARE‐TIMI 58 study. Methods: Patients with new initiation of dapagliflozin and/or other GLDs were identified in Swedish nationwide healthcare registries for the period 2013 to 2016. Patients were included if they met the main DECLARE‐TIMI 58 inclusion criteria: age ≥40 years and established CV disease or presence of multiple‐risk factors, e.g. men aged ≥55 years and women aged ≥60 years with hypertension or dyslipidaemia. Propensity scores for the likelihood of dapagliflozin initiation were calculated, then 1:3 matching was carried out. DECLARE‐TIMI 58 outcomes were hospitalization for heart failure (HHF) or CV‐specific mortality, and major adverse CV events (MACE; CV‐specific mortality, myocardial infarction, or stroke). Cox survival models were used to estimate hazard ratios (HRs). Results: After matching, a total of 28 408 new‐users of dapagliflozin and/or other GLDs were identified, forming the population for the present study (henceforth referred to as the DECLARE‐like cohort. The mean age of this cohort was 66 years, and 34% had established CV disease. Dapagliflozin was associated with 21% lower risk of HHF or CV mortality versus other GLDs (HR 0.79, 95% confidence interval [CI] 0.69‐0.92) and had no significant association with MACE (HR 0.90, 95% CI 0.79‐1.03). HHF and CV mortality risks, separately, were lower at HR 0.79 (95% CI 0.67‐0.93) and HR 0.75 (95% CI 0.57‐0.97), respectively. Non‐significant associations were seen for myocardial infarction and stroke: HR 0.91 (95% CI 0.74‐1.11) and HR 1.06 (95% CI 0.87‐1.30), respectively. Conclusion: In a real‐world population similar to those included in the DECLARE‐TIMI 58 study, dapagliflozin was safe with regard to CV outcomes and resulted in lower event rates of HHF and CV mortality versus other GLDs. [ABSTRACT FROM AUTHOR]

Aims: To compare the sodium‐glucose‐cotransporter‐2 (SGLT‐2) inhibitor dapagliflozin with dipeptidyl peptidase‐4 (DPP‐4) inhibitors with regard to risk associations with major adverse cardiovascular (CV) events (MACE; non‐fatal myocardial infarction, non‐fatal stroke or cardiovascular mortality), hospitalization for heart failure (HHF), atrial fibrillation and severe hypoglycaemia in patients with type 2 diabetes (T2D) in a real‐world setting. Methods: All patients with T2D prescribed glucose‐lowering drugs (GLDs) during 2012 to 2015 were identified in nationwide registries in Denmark, Norway and Sweden. Patients were divided into two groups: new users of dapagliflozin and new users of DPP‐4 inhibitors, matched 1:3 by propensity score, calculated by patient characteristics, comorbidities and drug treatment. Cox survival models were used to estimate hazard ratio (HR) per country separately, and a weighted average was calculated. Results: After matching, a total of 40 908 patients with T2D were identified as new users of dapagliflozin (n = 10 227) or a DPP‐4 inhibitor (n = 30 681). The groups were well balanced at baseline; their mean age was 61 years and 23% had CV disease. The mean follow‐up time was 0.95 years, with a total of 38 760 patient‐years. Dapagliflozin was associated with a lower risk of MACE, HHF and all‐cause mortality compared with DPP‐4 inhibitors: HRs 0.79 (95% confidence interval [CI] 0.67‐0.94), 0.62 (95% CI 0.50‐0.77), and 0.59 (95% CI 0.49‐0.72), respectively. Numerically lower, but non‐significant HRs were observed for myocardial infarction (0.91 [95% CI 0.72‐1.16]), stroke (0.79 [95% CI 0.61‐1.03]) and CV mortality (0.76 [95% CI 0.53‐1.08]) Neutral associations with atrial fibrillation and severe hypoglycaemia were observed. Conclusions: Dapagliflozin was associated with lower risks of CV events and all‐cause mortality compared with DPP‐4 inhibitors in a real‐world clinical setting and a broad T2D population. [ABSTRACT FROM AUTHOR]

Aims To investigate the association of novel oral glucose-lowering drugs ( GLDs), compared with that of insulin, with risk of all-cause mortality, cardiovascular disease ( CVD) and severe hypoglycaemia. Methods During 2013 to 2014 all patients with type 2 diabetes in Sweden identified as new users of novel oral GLDs, either dipeptidyl peptidase-4 ( DPP-4) inhibitors or sodium-glucose cotransporter-2 ( SGLT2) inhibitors (only dapagliflozin available in Sweden during the study period), with those initiating insulin as a comparison group, in the Prescribed Drug Register were included and followed in the Patient and Cause of Death Registers. The novel GLD group and insulin group were matched 1:1 using propensity score. Cox regression models were used to estimate risks. Results Of 37 603 patients, 21 758 were matched 1:1 to novel GLD vs insulin groups, with median follow-up times of 1.51 years (16 304 patient-years) and 1.53 years (16 306 patient-years), respectively. Treatment with novel GLDs was associated with a 44% (hazard ratio [ HR] 0.56 [95% confidence interval { CI} 0.49-0.64]), 15% ( HR 0.85 [95% CI 0.73-0.99]) and 74% (0.26 [95% CI 0.12-0.57]) lower risk of all-cause mortality, CVD and hypoglycaemia, respectively, compared with insulin treatment. In separate analyses for the two novel GLDs, dapagliflozin was associated with lower risks of all-cause mortality and CVD (56% [ HR 0.44, 95% CI 0.28-0.70] and 49% [ HR 0.51, 95% CI 0.30-0.86], respectively), while DPP-4 inhibitor treatment was associated with lower risk of all-cause mortality (41% [ HR 0.59, 95% CI 0.51-0.67]), but not with CVD ( HR 0.87, 95% CI 0.75-1.01). Conclusions Novel oral GLD treatment was associated with lower risk of all-cause mortality, CVD and severe hypoglycaemia compared with insulin treatment. Dapagliflozin was associated with a lower risk of both all-cause mortality and CVD, whereas DPP-4 inhibitor treatment was only associated with lower risk of all-cause mortality. [ABSTRACT FROM AUTHOR]

Hypoglycaemia is a common side-effect of glucose-lowering therapies for type-2 diabetic patients, which may cause cognitive/neurological impairment. Although the effects of hypoglycaemia in the brain have been extensively studied in neurons, how hypoglycaemia impacts the viability of adult neural stem cells (NSCs) has been poorly investigated. In addition, the cellular and molecular mechanisms of how hypoglycaemia regulates NSCs survival have not been characterized. Recent work others and us have shown that the pituitary adenylate cyclase-activating polypeptide (PACAP) and the glucagon-like peptide-1 receptor (GLP-1R) agonist Exendin-4 stimulate NSCs survival against glucolipoapoptosis. The aim of this study was to establish an in vitro system where to study the effects of hypoglycaemia on NSC survival. Furthermore, we determine the potential role of PACAP and Exendin-4 in counteracting the effect of hypoglycaemia. A hypoglycaemic in vitro milieu was mimicked by exposing subventricular zone-derived NSC to low levels of glucose. Moreover, we studied the potential involvement of apoptosis and endoplasmic reticulum stress by quantifying protein levels of Bcl-2, cleaved caspase-3 and mRNA levels of CHOP. We show that PACAP via PAC-1 receptor and PKA activation counteracts impaired NSC viability induced by hypoglycaemia. The protective effect induced by PACAP correlated with endoplasmic reticulum stress, Exendin-4 was ineffective. The results show that hypoglycaemia decreases NSC viability and that this effect can be substantially counteracted by PACAP via PAC-1 receptor activation. The data supports a potential therapeutic role of PAC-1 receptor agonists for the treatment of neurological complications, based on neurogenesis impairment by hypoglycaemia. [ABSTRACT FROM AUTHOR]

Background: The vascular effects exerted by GLP-1 are mediated by several synergistic mechanisms such as involvement of nitric oxide and natriuresis. Recently, it was demonstrated that atrial natriuretic peptide (ANP) is essential for the glucagon-like peptide-1 (GLP-1)-stimulated vascular smooth muscle relaxation that mediates anti-hypertensive action in rodents. Therefore a GLP-1-ANP axis has been suggested. The aim of this study was to investigate whether this effect can be demonstrated in patients with type 2 diabetes and congestive heart failure. Methods: The study was a post hoc analysis of a randomized double-blinded, placebo-controlled trial. Twenty male patients with type 2 diabetes and congestive heart failure were randomized to receive a 6-h infusion of exenatide or placebo. Cardiac filling pressures were measured by right heart catheterization, and plasma levels of ANP, N-terminal pro-brain natriuretic peptide, and exenatide were measured at baseline and at the end of the exenatide infusion. Results: Exenatide infusion resulted in a significant decrease of circulating ANP levels compared with placebo, concomitant with a decrease in pulmonary capillary wedge pressure (PCWP), pulmonary artery pressure (PAP) and right arterial pressure (RAP), and increased cardiac output. There was no correlation between plasma ANP levels and exenatide levels. A negative correlation between ANP levels and PCWP, PAP, and RAP, which remained significant after adjustment for plasma exenatide levels, was demonstrated during exenatide infusion. Conclusions: Exenatide infusion decreases cardiac filling pressure and ANP levels. The reduction of ANP levels was primarily because of the reduction in cardiac filling pressure, independent of exenatide levels. It seems unlikely that this was mediated via ANP. Trial registration: http://www.isrctn.org/ISRCTN47533126 [ABSTRACT FROM AUTHOR]

Exendin-4 is a glucagon-like receptor 1 agonist clinically used against type 2 diabetes that has also shown neuroprotective effects in experimental stroke models. However, while the neuroprotective efficacy of Exendin-4 has been thoroughly investigated if the pharmacological treatment starts before stroke, the therapeutic potential of the Exendin-4 if the treatment starts acutely after stroke has not been clearly determined. Further, a comparison of the neuroprotective efficacy in normal and aged diabetic mice has not been performed. Finally, the cellular mechanisms behind the efficacy of Exendin-4 have been only partially studied. The main objective of this study was to determine the neuroprotective efficacy of Exendin-4 in normal and aged type 2 diabetic mice if the treatment started after stroke in a clinically relevant setting. Furthermore we characterized the Exendin-4 effects on stroke-induced neuroinflammation. Two-month-old healthy and 14-month-old type 2 diabetic/obese mice were subjected to middle cerebral artery occlusion. 5 or 50 µg/kg Exendin-4 was administered intraperitoneally at 1.5, 3 or 4.5 hours thereafter. The treatment was continued (0.2 µg/kg/day) for 1 week. The neuroprotective efficacy was assessed by stroke volume measurement and stereological counting of NeuN-positive neurons. Neuroinflammation was determined by gene expression analysis of M1/M2 microglia subtypes and pro-inflammatory cytokines. We show neuroprotective efficacy of 50 µg/kg Exendin-4 at 1.5 and 3 hours after stroke in both young healthy and aged diabetic/obese mice. The 5 µg/kg dose was neuroprotective at 1.5 hour only. Proinflammatory markers and M1 phenotype were not impacted by Exendin-4 treatment while M2 markers were significantly up regulated. Our results support the use of Exendin-4 to reduce stroke-damage in the prehospital/early hospitalization setting irrespectively of age/diabetes. The results indicate the polarization of microglia/macrophages towards the M2 reparative phenotype as a potential mechanism of neuroprotection. [ABSTRACT FROM AUTHOR]

Abstract: Exenatide (synthetic exendin-4) is a stable analogue of glucagon-like peptide 1 (GLP-1) and has recently been approved for clinical use against type 2 diabetes. Exenatide is believed to exert its effects via the GLP-1 receptor with almost the same potency as GLP-1 in terms of lowering blood glucose. Short term exenatide treatment normalizes the altered vascular tone in type 2 diabetic rats, probably due to the reduction in glycemia. The aim of this study was to investigate whether exenatide directly protects against triglyceride-induced endothelial dysfunction in rat femoral arterial rings ex vivo. Short term pre-incubation with Intralipid® (0.5 and 2%) was found to dose-dependently induce endothelial dysfunction, in that it elicited a significant reduction in ACh-induced vasorelaxation by 29% and 35%, respectively. Paradoxically, this occurred with a concomitant increase in endothelial nitric oxide synthase (eNOS) activity. No such reduction in vasorelaxation by Intralipid® was seen in response to the NO donor sodium nitroprusside (SNP), revealing an endothelium-dependent vascular dysfunction by Intralipid®. However, exenatide did not protect against Intralipid®-induced endothelial dysfunction. More surprisingly, the maximum vasorelaxation induced by exenatide (without Intralipid®) was only 3±2%, compared to the 23±4%, 38±4%, 79±3% and 97±4% relaxations induced by GLP-1, GLP-1 (9-36), ACh and SNP, respectively. This unexpected finding prompted us to ascertain that the exenatide preparation was biologically active, and both exenatide (10−11 mol/l) and GLP-1 (10−9 mol/l) significantly increased insulin secretion in pancreatic β-cells from ob/ob mice in vitro. In conclusion, exenatide could neither confer any acute protective effects against triglyceride-induced endothelial dysfunction nor exert any significant vasorelaxant actions in this model of rat conduit arteries ex vivo. [Copyright &y& Elsevier]

Abstract: Cardiovascular disease is by far the most common complication of type 2 diabetes and also the most serious one. Suffering from type 2 diabetes mellitus not only dramatically increases the risk of cardiovascular disease but is also associated with poor survival, both acutely and in the long term after a myocardial infarction. In fact, total mortality from coronary artery disease in subjects with type 2 diabetes mellitus, without a previous myocardial infarction, is as high as that of non-diabetic individuals with a previous infarction. Intense research efforts have thus been directed towards exploring the reasons for why particularly type 2 diabetic patients have such a poor prognosis suffering from cardiovascular disease. Obesity-related type 2 diabetes (“diabesity”), including the metabolic syndrome, is rapidly rising in prevalence. About 80% of all type 2 diabetes co-exists with insulin resistance. Endothelial dysfunction is a ubiquitous abnormality in insulin-resistant states that might contribute to premature atherosclerosis in a multifactorial and complex way. Low grade inflammation may play a role in development insulin resistance and type 2 diabetes and it has been proposed that atherosclerosis is basically an inflammatory disease. Thus, the pathophysiology of insulin resistance, the metabolic syndrome, and atherosclerosis may share inflammatory basis as a common denominator. Also, insulin resistance is not confined to skeletal muscle, adipose tissue and the liver, but also to the endothelium. Insulin resistance and endothelial dysfunction co-exist, where chronic inflammation may be a crucial factor. Accordingly, the possibility that physical activity or pharmacological agents that increase insulin sensitivity also improve endothelial function, or vice versa, has been investigated. Many different alterations in life style and drugs that improve endothelial function are known to lower the risk of contracting diabetes. In this review, the pharmacological treatment available against type 2 diabetes mellitus is discussed with particular emphasis on its impact on the endothelium. [Copyright &y& Elsevier]

The article presents comment on the study regarding the lower risk of death in associated with sodium–glucose cotransporter 2 inhibitors (SGLT2i) compared with insulin treatment in a broad population with type 2 diabetes. It examines the different issues in the study and recognizes the risks of biases in the treatments. The authors argue that observational studies can provide relevant new knowledge about the efficacy of different treatments in real clinical setting.

Aims: The objective of this nationwide study was to compare the risk of all-cause mortality, fatal and nonfatal cardiovascular disease (CVD), and severe hypoglycemia in patients with type 2 diabetes (T2D) on metformin monotherapy treatment starting second-line treatment with either insulin or dipeptidyl peptidase-4 inhibitor (DPP-4i).Methods: All patients with T2D in Sweden who initiated second-line treatment with insulin or DPP-4i after metformin monotherapy during 2007-2014 identified in the Swedish Prescribed Drug Register were followed for outcome in the Cause of Death and National Patient Registers. Insulin and DPP-4i patients were matched 1:1 using propensity-score matching. Comparisons between groups were performed using unadjusted Cox regression models. Additionally, multivariate adjusted survival models were used to test the results using the full population without matching.Results: Of 27,767 mono-metformin-treated patients, 55.7% started insulin and 44.3% a DPP-4i, and after matching both groups had 9278 patients each. Median follow-up (patients years) times were 3.84 (37,578) and 3.93 (37,983) for insulin and DPP-4i-groups, respectively. Insulin compared with DPP-4i was associated with higher risk of subsequent all-cause mortality, fatal and nonfatal CVD, and severe hypoglycemia; adjusted HR (95% CI): 1.69 (1.45-1.96); 1.39 (1.21-1.61); and 4.35 (2.26-8.35), respectively. When performing multivariate adjusted analyses on the full population similar results were found.Conclusions: Initiation of insulin, compared with DPP-4i treatment, was associated with an increased risk of subsequent all-cause mortality, fatal and nonfatal CVD, and severe hypoglycemia. Results from randomized trials will be important to elucidate causal relationships. [ABSTRACT FROM AUTHOR]

Aims: There are safety concerns related to sulphonylurea treatment. The objective of this nationwide study was to compare the risk of cardiovascular disease (CVD), all-cause mortality and severe hypoglycemia in patients with type 2 diabetes (T2D) starting second-line treatment with either metformin+sulphonylurea or metformin+dipeptidyl peptidase-4 inhibitor (DPP-4i).Methods: All patients with T2D in Sweden who initiated second-line treatment with metformin+sulphonylurea or metformin+DPP-4i during 2006-2013 (n=40,736 and 12,024, respectively) were identified in this nationwide study. The Swedish Prescribed Drug Register and the Cause of Death and National Patient Registers were used, and Cox survival models adjusted for age, sex, fragility, prior CVD, and CVD-preventing drugs were applied to estimate risks of events. Propensity score adjustments and matching methods were used to test the results.Results: Of 52,760 patients; 77% started metformin+SU and 23% metformin+DPP-4i. Crude incidences for severe hypoglycemia, CVD, and all-cause mortality in the SU cohort were 2.0, 19.6, and 24.6 per 1000 patient-years and in the DPP-4i cohort were 0.8, 7.6, and 14.9 per 1000 patient-years, respectively. Sulphonylurea compared with DPP4i was associated with higher risk of subsequent severe hypoglycemia, fatal and nonfatal CVD, and all-cause mortality; adjusted HR (95% CI): 2.07 (1.11-3.86); 1.17 (1.01-1.37); and 1.25 (1.02-1.54), respectively. Results were confirmed by additional propensity-adjusted and matched analyses. Among the SU drugs, glibenclamide had the highest risks.Conclusions: Metformin+SU treatment was associated with an increased risk of subsequent severe hypoglycemia, cardiovascular events, and all-cause mortality compared with metformin+DPP4i. Results from randomized trials will be important to elucidate causal relationships. [ABSTRACT FROM AUTHOR]

The objective was to identify candidate patient reported outcomes with potential to inform individual patient care and service development for inclusion in a digital outcome set to be collected in routine care, as part of an international project to enhance care outcomes for people with diabetes. PubMed, COSMIN and COMET databases were searched. Published studies were included if they recommended patient reported outcomes that were clinically useful and/or important to people with diabetes. To aid selection decisions, recommended outcomes were considered in terms of the evidence endorsing them and their importance to people with diabetes. Twenty-seven studies recommending 53 diabetes specific outcomes, and patient reported outcome measures, were included. The outcomes reflected the experience of living with diabetes (e.g. psychological well-being, symptom experience, health beliefs and stigma) and behaviours (e.g. self-management). Diabetes distress and self-management behaviours were most endorsed by the evidence. The review provides a comprehensive list of candidate outcomes endorsed by international evidence and informed by existing outcome sets, and suggestions for measures. The review offers evidence to guide clinical application. Integrated measurement of these outcomes in care settings holds enormous potential to improve provision of care and outcomes in diabetes. • A broad range of patient reported outcomes is recommended for routine diabetes care. • Diabetes distress and self-management behaviours are most endorsed by evidence. • This review provides evidence to direct decisions about which outcomes to collect. • Validated tools are suggested for measuring each of the recommended outcomes. [ABSTRACT FROM AUTHOR]