Reduction of prevalence of patients meeting the criteria for metabolic syndrome with tirzepatide: a post hoc analysis from the SURPASS Clinical Trial Program.

BACKGROUND: Metabolic syndrome is characterized as the co-occurrence of interrelated cardiovascular risk factors, including insulin resistance, hyperinsulinemia, abdominal obesity, dyslipidemia and hypertension. Once weekly tirzepatide is approved in the US and EU for the treatment of type 2 diabetes (T2D) and obesity. In the SURPASS clinical trial program for T2D, tirzepatide demonstrated greater improvements in glycemic control, body weight reduction and other cardiometabolic risk factors versus placebo, subcutaneous semaglutide 1 mg, insulin degludec, and insulin glargine. This post hoc analysis assessed the effect of tirzepatide use on the prevalence of patients meeting the criteria for metabolic syndrome across SURPASS 1-5. METHODS: Metabolic syndrome was defined as having ≥ 3 of 5 criteria according to the US National Cholesterol Education Program: Adult Treatment Panel III. Analyses were based on on-treatment data at the primary endpoint from patients adherent to treatment (taking ≥ 75% study drug). A logistic regression model with metabolic syndrome status as the response variable, metabolic syndrome status at the baseline visit as an adjustment, and randomized treatment as fixed explanatory effect was used. The effect of tirzepatide use on the prevalence of patients meeting the criteria for metabolic syndrome by categorical weight loss, background medication and gender were assessed. RESULTS: In SURPASS, the prevalence of patients meeting the criteria for metabolic syndrome at baseline was 67-88% across treatment groups with reductions at the primary endpoint to 38-64% with tirzepatide versus 64-82% with comparators. Reductions in the prevalence of patients meeting the criteria for metabolic syndrome was significantly greater with all tirzepatide doses versus placebo, semaglutide 1 mg, insulin glargine, and insulin degludec (p < 0.001). Individual components of metabolic syndrome were also reduced to a greater extent with tirzepatide vs comparators. Greater reductions in body weight were associated with greater reductions in the prevalence of patients meeting the criteria for metabolic syndrome and its individual components. Background SGLT2i or sulfonylurea use or gender did not impact the change in prevalence of patients meeting the criteria for metabolic syndrome. CONCLUSIONS: In this post hoc analysis, tirzepatide at all doses studied was associated with a greater reduction in the prevalence of patients meeting the criteria for metabolic syndrome compared to placebo, semaglutide 1 mg, insulin degludec, and insulin glargine. Although more evidence is needed, these data would support greater potential improvement in cardiovascular risk factor profile with tirzepatide treatment in people across the continuum of T2D.

Glycaemic variability in patients with type 2 diabetes mellitus treated with dulaglutide, with and without concomitant insulin: Post hoc analyses of randomized clinical trials.

AIM: To investigate the association between treatment with dulaglutide and glycaemic variability (GV) in adult patients with type 2 diabetes mellitus (T2D). MATERIALS AND METHODS: Post hoc analyses of six randomized, phase 3 studies were conducted to investigate the association between treatment with dulaglutide 1.5 mg once weekly and GV in adult patients with T2D. Using data from seven- and eight-point self-monitored plasma glucose (SMPG) profiles over up to 28 weeks of treatment, GV in within- and between-day SMPG, and between-day fasting glucose from SMPG (FSMPG) was assessed according to standard deviation and coefficient of variation. RESULTS: Pooled data from five studies with dulaglutide as monotherapy or added to oral glucose-lowering medication, without concomitant insulin treatment, revealed clinically meaningful reductions in within- and between-day SMPG, and between-day FSMPG variability from baseline in the dulaglutide group. Comparisons between treatment groups in two studies demonstrated that reductions from baseline in within-day and between-day SMPG, and between-day FSMPG variability were greater for treatment with dulaglutide compared with insulin glargine, as well as for treatment with dulaglutide when added to insulin glargine compared with insulin glargine alone. CONCLUSIONS: In patients with T2D, treatment with dulaglutide as monotherapy or added to oral glucose-lowering medication, without concomitant insulin treatment, was potentially associated with a reduction in GV. Treatment with dulaglutide was associated with a reduction in GV to a greater degree than insulin glargine. When added to insulin glargine, treatment with dulaglutide was associated with greater decreases in GV compared with insulin glargine alone. As reduced GV may be associated with better outcomes, these findings may have clinical relevance.

A paired trial comparing mononuclear cell collection in two machines for further inactivation through an inline or offline extracorporeal photopheresis procedure.

BACKGROUND: Extracorporeal photopheresis (ECP) is an effective treatment. However, protocols differ widely, and some questions, such as the number of cells to be collected or the number of ECP treatment days per treatment cycle, are still unsolved. The aim of this study was to compare a multistep (offline) (Spectra Optia and Macogenic G2) against an integrated (inline) ECP system (Therakos Cellex system) with respect to mononuclear cell (MNC) collection. STUDY DESIGN AND METHODS: The number and quality parameters of the MNC products collected were evaluated together with some machine parameters, such as collection time. Comparisons were made through paired sample analysis with the t test. RESULTS: Fourteen patients underwent 15 double-paired procedures using both ECP protocols. The average MNC collected in the multistep procedure was 77.4 × 108 , four times more than in the integrated procedure (18.5 × 108 ). MNC purity (84.4% vs. 63.8%) and enrichment (27.9 vs. 5.9) in the product collected were also higher in the multistep procedure. The whole ECP time was higher in the multistep than in the integrated procedure (272 vs. 106 min), but the calculated time to collect 25 × 108 MNCs in the multistep was shorter compared with the one-step procedure (77.8 vs. 172 min). All these differences between the two protocols were statistically significant. CONCLUSIONS: These two ECP protocols are different with respect to MNC collection and length of procedure. Some unresolved questions, such as the better MNC dose to inactivate or the number of consecutive days that ECP should be performed for optimal clinical efficacy, require further review.

Dulaglutide is an effective treatment for lowering HbA1c in patients with type 2 diabetes regardless of body mass index.

AIM: To assess the relationship between baseline body mass index (BMI) and glycaemic control in dulaglutide-treated patients, a post hoc analysis was conducted on HbA1c and baseline BMI data from eight AWARD studies, with a total of 5770 patients. MATERIALS AND METHODS: Changes from baseline in HbA1c data from patients treated with 1.5 mg or 0.75 mg dulaglutide, active comparator or placebo, were analyzed in each study (AWARD-1 to -6, -8 and - 9) at approximately 6 months (26, 24 and 28 weeks, respectively). Within each study, data were analyzed by the following baseline BMI categories: <30, ≥30 to <35, and ≥ 35 kg/m2 . RESULTS: In this post hoc analysis, 1.5 mg or 0.75 mg dulaglutide treatment achieved statistically significant HbA1c reductions from baseline in all BMI categories (least-squares mean change from -0.62 to -1.75%) across the AWARD studies. No statistically significant treatment-by-BMI category interactions were found for reductions in HbA1c. CONCLUSION: This post hoc analysis of eight AWARD studies indicates that baseline BMI does not affect the relative treatment efficacy of dulaglutide as measured by HbA1c change from baseline in any study. Dulaglutide is an effective treatment option for adult patients with type 2 diabetes regardless of their baseline BMI category.

Broader conceptualization of remission assessed by the remission from depression questionnaire and its association with symptomatic remission: a prospective, multicenter, observational study.

BACKGROUND: Goals of treating major depressive disorder (MDD) include achieving remission and avoiding relapse. It is possible that patients may have a broader view of remission than what is captured via clinician-rated scales. This patient perspective may, in turn, have an impact on treatment outcomes. METHODS: The association between a broader conceptualization of remission, based on the Remission from Depression Questionnaire (RDQ) score at baseline, and being in symptomatic remission after 6 months was evaluated in subjects (N = 613) with MDD in symptomatic remission at baseline (17-item Hamilton Rating Scale for Depression [HAMD-17] ≤7). Specific aspects of depression were assessed from physician and patient perspectives as secondary endpoints. A backwards selection strategy was used to statistically model remission status and determine association of factors with potential to influence remission. RESULTS: At month 6, after adjustment for baseline HAMD-17 score, there was no association between baseline RDQ score and symptomatic remission status (HAMD-17), relapse, composite remission status, healthcare resource utilization, or quality of life. There was no association between functional impairment scores at baseline (Sheehan Disability Scale and Social and Occupational Functioning Assessment Scale) and symptomatic remission status (HAMD-17) at month 6. CONCLUSIONS: This study indicates that RDQ-constructs are independent from symptomatic remission. Symptom severity at study entry appeared to be the only significant predictor of eventual relapse during the 6-month follow-up period. However, our results also suggest that the current definition of remission that is based on symptom reduction should be further elaborated and that alternative or additional definitions should be considered in determining remission.

Disease and Economic Burden of Poor Metabolic and Weight Control in Type 2 Diabetes in Spain: A Systematic Literature Review.

INTRODUCTION: Poor metabolic control and excess body weight are frequently present in people with type 2 diabetes (PwT2D). METHODS: A systematic literature review was conducted to identify observational studies reporting clinical, economic, and health-related quality of life (HRQoL) outcomes associated with poor metabolic (according to HbA1c, blood pressure [BP] and low density lipoprotein cholesterol [LDL-C] levels) and/or weight control (defined by a body mass index [BMI] ≥ 30 kg/m2) in adults with T2D in Spain, including articles published in either Spanish or English between 2013 and 2022 and conference abstracts from the last 2 years. RESULTS: Nine observational studies were included in the analysis. Poor glycemic control (HbA1c ≥ 7%) was associated with cardiovascular disease (CVD), increased requirements for antidiabetic medications, higher and more frequent weight gain, a greater probability of hypoglycemia and dyslipidemia, and worse health-related quality of life (HRQoL). Uncontrolled BP in PwT2D was related with the presence of CVD, worse metabolic control, and higher BMI and abdominal perimeter values. Poor LDL-C control or dyslipidemia was associated with CVD, hypoglycemia, and elevated HbA1c and triglycerides levels. The presence of a BMI ≥ 30 kg/m2 was related to CVD and hypoglycemia, a higher prevalence of metabolic syndrome and worse BP control. Direct medical costs were found to be higher in PwT2D when coexisting with HbA1c levels ≥ 7%, uncontrolled BP or obesity. Increased total costs, including productivity losses, were also detected in those who presented uncontrolled BP and a BMI ≥ 30 kg/m2, and when poor weight control existed together with HbA1c ≥ 8% and poorly controlled BP. CONCLUSION: Gathered evidence supports the high clinical, economic and HRQoL burden of poor metabolic and/or weight control in PwT2D in Spain and reinforces the importance of prioritizing its control to reduce the associated burden, at both the individual and healthcare system levels.

Use of Tirzepatide in Adults with Type 2 Diabetes Mellitus: Scientific Evidence and Practical Aspects.

Tirzepatide is a novel antidiabetic medication a single-molecule, agonist to the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors. It is approved in the USA and EU for the treatment of type 2 diabetes mellitus (T2DM) and obesity. Due to the potential novelty represented by incorporating tirzepatide to clinical practice, we aim to review practical aspects of tirzepatide use in T2DM and the supporting scientific evidence. A group of ten endocrinologists involved as investigators in the phase 3 SURPASS clinical trial program followed a nominal group technique, a qualitative research methodology designed as a semi-structured group discussion to reach a consensus on the selection of a set of practical aspects. The scientific evidence for tirzepatide has been reviewed with respect to a number of patients' clinical profiles and care goals. Information of interest related to adverse events, special warnings and precautions, and other considerations for tirzepatide use has been included. Finally, information provided to the patients has been summarized. The practical aspects reported herein may be helpful in guiding physicians in the use of tirzepatide and contribute to optimizing the management of T2DM.

Residual symptoms and functioning in depression, does the type of residual symptom matter? A post-hoc analysis.

BACKGROUND: The degrees to which residual symptoms in major depressive disorder (MDD) adversely affect patient functioning is not known. This post-hoc analysis explored the association between different residual symptoms and patient functioning. METHODS: Patients with MDD who responded (≥50% on the 17-item Hamilton Rating Scale for Depression; HAMD-17) after 3 months of treatment (624/930) were included. Residual core mood-symptoms (HAMD-17 core symptom subscale ≥1), residual insomnia-symptoms (HAMD-17 sleep subscale ≥1), residual anxiety-symptoms (HAMD-17-anxiety subscale ≥1), residual somatic-symptoms (HAMD-17 Item 13 ≥1), pain (Visual Analogue Scale ≥30), and functioning were assessed after 3 months treatment. A stepwise logistic regression model with normal functioning (Social and Occupational Functioning Assessment Scale ≥80) as the dependent variable was used. RESULTS: After 3 months, 59.5% of patients (371/624) achieved normal functioning and 66.0% (412/624) were in remission. Residual symptom prevalence was: core mood symptoms 72%; insomnia 63%; anxiety 78%; and somatic symptoms 41%. Pain reported in 18%. Factors associated with normal functioning were absence of core mood symptoms (odds ratio [OR] 8.7; 95% confidence interval [CI], 4.6-16.7), absence of insomnia symptoms (OR 1.8; 95% CI, 1.2-2.7), episode length (4-24 weeks vs. ≥24 weeks [OR 2.0; 95% CI, 1.1-3.6]) and better baseline functioning (OR 1.0; 95% CI, 1.0-1.1). A significant interaction between residual anxiety symptoms and pain was found (p = 0.0080). CONCLUSIONS: Different residual symptoms are associated to different degrees with patient functioning. To achieve normal functioning, specific residual symptoms domains might be targeted for treatment.

Systematic depression screening in high-risk patients attending primary care: a pragmatic cluster-randomized trial.

BACKGROUND: Systematic screening for depression in high-risk patients is recommended but remains controversial. The aim of this study was to assess the effectiveness of such screening in everyday clinical practice on depression recognition. METHODS: A pragmatic, cluster randomized, controlled study that randomized primary care physicians (PCPs) in Spain either to an intervention or control group. The intervention group (35-PCPs) received training in depression screening and used depression screening routinely for at least 6 months. The control group (34-PCPs) managed depression in their usual manner. Adherence to (1-6; never-very frequently), feasibility (1-4; unfeasible-very feasible), and acceptance (1-5; very poor-very good) of the screening were evaluated. Underrecognition (primary outcome) and undertreatment rates of major depressive disorder (MDD) in the two groups were compared 6 months after randomization in a random sample of 3737 patients assigned to these PCPs using logistic regression adjusting for the clustering effect. RESULTS: No significant differences were found for recognition rates (58.0% vs. 48.1% intervention vs. control; OR [95%CI] 1.40 [0.73-2.68], p = 0.309). The undertreatment rate did not differ significantly either (p = 0.390). The mean adherence to depression screening was 4.4 ± 1.0 ('occasionally'), the mean feasibility was 3.1 ± 0.5 ('moderately feasible'), and the mean acceptance was 4.2 ± 0.6 ('good'). CONCLUSIONS: This research was not able to show effectiveness of the systematic screening for MDD in high-risk patients on depression recognition in primary care. The poor adherence to screening implementation could partially explain the results. These reflect the difficulties of putting into practice the clinical guidelines usually based on interventional research. TRIAL REGISTRATION: Clinicaltrials.gov NCT01662817.

Remission and functioning in major depressive disorder.

Evidence from numerous clinical studies has shown that the optimal goal for the treatment of depression is remission. Remission implies that the signs and symptoms of the disease are absent or virtually absent, which is typically associated with a return to the patient s previous daily functioning. Functioning in depression is a broad concept that covers different domains. There are many validated instruments for its assessment, these being reviewed in this article. Furthermore, recovering the pre-morbid level of functioning level is increasingly being identified as a significant target in addition to symptomatic remission. In this sense, functional recovery has been associated with better prognosis of depression and is also a clinical goal expressed by the patient. Several factors, like complete remission of symptoms, with no residual symptoms, maintenance of remission, quality of remission, early remission, have been identified as contributors to functional recovery. In order to facilitate the clinical outcomes, evaluation of and search for symptomatic remission as well as functional recovery need to be integrated into the clinical practice.

Glycaemic Control and Weight Reduction: A Narrative Review of New Therapies for Type 2 Diabetes.

Early and intensive treatment of type 2 diabetes (T2D) has been associated with lower risk of diabetes-related complications. Control of overweight and obesity, which are strongly associated with T2D and many of its complications, is also key in the management of the disease. New therapies allow for individualised glycaemic control targets with greater safety. Thus, in patients with a higher cardiovascular and renal risk profile, current guidelines encourage early treatment with metformin together with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose co-transporter-2 inhibitors with proven cardiovascular benefit. GLP-1 RAs combine highly efficacious glucose-lowering activity with a reduced risk of hypoglycaemia. Recently, tirzepatide, a first-in-class drug that activates both glucose-dependent insulinotropic polypeptide and GLP-1 receptors, has demonstrated very high efficacy in glycated haemoglobin (HbA1c) and weight reduction in clinical trials. Tirzepatide has the potential to help people with T2D reach recommended glycaemic and weight targets (HbA1c < 7% and > 5% weight reduction) and to allow some patients to reach HbA1c measurements close to normal physiological levels and substantial weight reduction. In 2022, tirzepatide was approved by the US Food and Drug Administration and the European Medicines Agency for treatment of people with T2D and is currently in development for chronic weight management.

In people newly diagnosed with type 2 diabetes, early and intensive treatment of the disease can help control blood sugar and reduce the risk of later complications. The need to control weight in people with obesity and diabetes has also recently become a priority. New drugs developed in recent years allow for better and more individualised management of blood sugar without the risk of blood sugar levels dropping too low. In patients at risk of kidney or heart disease, the current recommendation is early treatment with metformin and drugs with proven cardiovascular benefit. Tirzepatide is a new drug that has also demonstrated very high efficacy in reducing blood glucose and body weight. It has the potential to help people with type 2 diabetes achieve their goals and prevent other diabetes-related complications. It is likely that some patients will even be able to bring their blood glucose to normal levels and lose substantial amounts of weight. The US and European regulatory agencies approved tirzepatide in 2022 for the treatment of type 2 diabetes and it is currently being tested for chronic weight management.

Functional, Physical, and Volatile Characterization of Chitosan/Starch Food Films Functionalized with Mango Leaf Extract.

Active packaging is one of the currently thriving methods to preserve highly perishable foods. Nonetheless, the integration of active substances into the formulation of the packaging may alter their properties-particularly mass transfer properties-and therefore, the active compounds acting. Different formulations of chitosan (CH), starch (ST), and their blends (CH-ST), with the addition of mango leaf extract (MLE) have been polymerized by casting to evaluate their food preservation efficiency. A CH-ST blend with 3% MLE using 7.5 mL of the filmogenic solution proved to be the most effective formulation because of its high bioactivity (ca. 80% and 74% of inhibition growth of S. aureus and E. coli, respectively, and 40% antioxidant capacity). The formulation reduced the water solubility and water vapor permeability while increasing UV protection, properties that provide a better preservation of raspberry fruit after 13 days than the control. Moreover, a novel method of Headspace-Gas Chromatography-Ion Mobility Spectrometry to analyze the volatile profiles of the films is employed, to study the potential modification of the food in contact with the active film. These migrated compounds were shown to be closely related to both the mango extract additions and the film's formulation themselves, showing different fingerprints depending on the film.

GLP-1 RAs in Spain: A Short Narrative Review of Their Use in Real Clinical Practice.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are a class of drugs with potent glucose-lowering activity. Additionally, some GLP-1 RAs have demonstrated cardiovascular and renal benefits. Current guidelines recommend their use in patients with type 2 diabetes (T2D) at high risk of or with established cardiovascular disease (CVD), regardless of glycaemic control, with lifestyle modification and metformin. However, several studies have recently highlighted the limited number of patients with T2D benefiting from these medications worldwide. Given the huge burden of CVD among patients with T2D, efforts should be made to bring clinical practice closer to expert guidelines. This review describes the current situation of GLP-1 RA use in Spain and the reasons behind the gap between guidelines and real-world practice and suggests possible solutions. Administrative issues, lack of awareness of the cardiovascular benefits, clinical inertia, rejection of injectable medication and costs could be some of the reasons for the current situation. Possible strategies that could help to close the gap include encouraging a multidisciplinary approach to the treatment of diabetes which involves cardiologists, endocrinologists, nephrologists, primary care providers and pharmacists; improved awareness of comorbidities and earlier evaluation and treatment or risks; and better education of healthcare providers regarding the cardioprotective benefits of these drugs.

The glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are a class of drugs that can be beneficial for patients with type 2 diabetes who are at high risk of cardiovascular complications, such as heart attacks. For this reason, the current clinical guidelines strongly recommend their use in these patients. Unfortunately, many patients with type 2 diabetes and high cardiovascular risk still do not benefit from these drugs. This review analyses the reasons for this situation in Spain, and proposes some possible solutions. The reasons for the low use of GLP-1 RAs could be related to doctors not updating a patient's diabetes medicine as often as they should, lack of awareness about the cardiovascular benefits of these drugs, fear of medicines that involve needles, administrative issues, and costs. Some of the possible strategies to improve the use of GLP-1 RAs among patients with type 2 diabetes with high cardiovascular risk could be to foster greater cooperation among specialists, increase awareness of the need to treat cardiovascular risk in patients with diabetes, and better education of doctors regarding the benefits of these drugs.

Early switch strategy in patients with major depressive disorder: a double-blind, randomized study.

OBJECTIVE: Antidepressant switch is a commonly used strategy in the absence of an adequate response, but optimum timing is not well established. We compared the efficacy of an early and a conventional antidepressant switch strategy in patients with major depressive disorder. METHODS: Patients with no or minimal improvement (<30% reduction in baseline 17-item Hamilton Depression Rating Scale [HAMD17] score) after 4 weeks on escitalopram 10 mg/d were randomized to either early switch strategy with duloxetine 60 to 120 mg/d for 12 weeks (arm A) or conventional switch strategy (arm B): 4 further weeks on escitalopram 10 to 20 mg/d; then, in case of nonresponse (response, ≥ 50% reduction in HAMD17), switch to duloxetine 60 to 120 mg/d for 8 weeks, or continued escitalopram in responders. Co-primary end points were time to confirmed response and remission (HAMD17, ≤ 7). Strategies were compared using Kaplan-Meier, logistic regression, and repeated-measures analyses. RESULTS: Sixty-seven percent (566 of 840) of patients showed no or minimal improvement and were randomized to arm A (282 patients) or arm B (284 patients). No between-strategy differences in time to confirmed response (25% Kaplan-Meier estimates, 3.9 vs 4.0 weeks, P = 0.213) or remission (6.0 vs 7.9 weeks, P = 0.075) were found. Rates of confirmed responders were similar (64.9% vs 64.1%); however, more patients randomized to early switch achieved confirmed remission (43.3% vs 35.6%; P = 0.048). CONCLUSIONS: Although no differences in the primary end points were found, a higher remission rate was seen with the early switch strategy. Our findings suggest that further investigations to reevaluate the conventional approach to antidepressant switch strategy would be worthwhile.

Glucagon-Like Peptide-1 Receptor Agonist Use in People Living with Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Narrative Review of the Key Evidence with Practical Considerations.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are incretin-mimetic agents that are effective adjuncts in the treatment of diabetes. This class of medications is also associated with promoting weight loss and a low risk of hypoglycemia, and some have been shown to be associated with a significant reduction of major cardiovascular events. Mounting evidence suggests that GLP-1 RAs have benefits beyond reducing blood glucose that include improving kidney function in people living with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD), a common microvascular complication of T2DM. Several large clinical studies, the majority of which are cardiovascular outcome trials, indicate that GLP-1 RA therapy is safe and tolerable for people living with T2DM and compromised renal function, and also suggest that GLP-1 RAs may have renoprotective properties. Although evidence from clinical trials has shown GLP-1 RAs to be safe and efficacious in people living with T2DM and renal impairment, their use is uncommon in this patient population. With continuing developments in the field of GLP-1 RA therapy, it is important for physicians to understand the benefits and practical use of GLP-1 RAs, as well as the clinical evidence, in order to achieve positive patient outcomes. Here, we review evidence on GLP-1 RA use in people living with T2DM and CKD and summarize renal outcomes from clinical studies. We provide practical considerations for GLP-1 RA use to provide an added benefit to guide treatment in this high-risk patient population.

Type 2 diabetes mellitus (T2DM) is a common disorder characterized by insulin resistance and dysfunction of insulin-producing beta cells of the pancreas. People living with T2DM have an increased risk of developing complications, including chronic kidney disease (CKD), which itself is associated with increased mortality. Both the American Diabetes Association and Kidney Disease Improving Global Outcomes organization provide updated pharmacological recommendations for treating T2DM in people with CKD that include the use of sodium-glucose co-transporter-2 inhibitors (SGLT2i) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs). GLP-1 RAs are effective and safe treatments for controlling blood sugar levels and reducing body weight, and evidence from large clinical trials also suggests that GLP-1 RAs may be renoprotective. Despite the benefits of GLP-1 RAs, they are not commonly prescribed in people living with T2DM and CKD. Healthcare practitioners need to be aware of the most recent information so that they can make informed decisions when selecting treatment options. The objective of this review is to summarize the main renal outcomes from clinical studies while providing practical guidance on the use of GLP-1 RAs.

A Retrospective Observational Study Examining the Generalizability of Glucagon-Like Peptide 1 Receptor Agonist Cardiovascular Outcome Trials to the Real-World Population with Type 2 Diabetes in Spain: The REPRESENT Study.

INTRODUCTION: The REPRESENT study aims to examine whether participants enrolled in glucagon-like peptide 1 receptor agonist cardiovascular outcome trials (CVOTs) LEADER (liraglutide), REWIND (dulaglutide), and SUSTAIN-6 (injectable semaglutide) are representative of the Spanish population with type 2 diabetes (T2D). METHODS: This retrospective observational study used the IQVIA Electronic Medical Records database in Spain to identify adults aged 18 years and older with T2D diagnosed before/between January 2013 and December 2015. Demographic and clinical characteristics were analyzed descriptively. The proportions of individuals in the Spanish cohort who met the key selection criteria of each CVOT were calculated from individuals with available database entries for estimated glomerular filtration rate and body mass index using proxies. RESULTS: A total of 24,268 adults with T2D were identified from the IQVIA database. The Spanish cohort was predominantly male (55.5%) and had a mean (± SD) age of 66.8 ± 12.5 years and HbA1c of 7.2 ± 1.5%, with 14.0% having established cardiovascular disease and 2.9% having prior myocardial infarction. The characteristics of the Spanish cohort were more similar to that of REWIND than LEADER or SUSTAIN-6. The proportions of subjects in the Spanish cohort who met the CVOTs key selection criteria were 10.1% for LEADER, 53.6% for REWIND, and 10.4% for SUSTAIN-6. CONCLUSIONS: Although none of the CVOTs was fully representative of the Spanish cohort, the REWIND population was found to be more representative of the real-world Spanish population with T2D than those of LEADER and SUSTAIN-6. These findings reinforce the applicability of the results of REWIND in clinical practice.

Optimal cutoff point of the Hamilton Rating Scale for Depression according to normal levels of social and occupational functioning.

The main goal in the treatment of major depressive disorder (MDD) is to achieve remission, defined as the resolution of symptoms and the return to normal levels of functionality. However, the clinical assessment of remission is usually merely based on scores of symptomatic rating scales. One of the most widely used scales to measure remission is the HAM-D(17), in which remission is defined as a score ≤ 7. Nevertheless, several studies have shown that this cutoff could be too high when also functioning is considered. This is a post-hoc analysis of a 6-month prospective study, performed over a sample of 292 Spanish patients with MDD, in order to find the optimal cutoff in the HAM-D(17) scale, considering normal levels of functionality, evaluated by the SOFAS; by means of plotting Receiver Operating Characteristics (ROC) curves. Our results show that a score of ≤ 5 maximized both sensitivity and specificity for identifying normal levels of functionality with respect to other scores, and thus agree with previous works, which suggest that a cutoff ≤ 7 might be too high to consider remission in patients with MDD, when normal levels of functioning are taken into account.

Functional impairment related to painful physical symptoms in patients with generalized anxiety disorder with or without comorbid major depressive disorder: post hoc analysis of a cross-sectional study.

BACKGROUND: Generalized anxiety disorder (GAD) is the most frequent anxiety disorder in primary care patients. It is known that painful physical symptoms (PPS) are associated with GAD, regardless the presence of comorbid major depressive disorder (MDD). However the specific role of such symptoms in patients' functional impairment is not well understood. The objective of the present study is to assess functional impairment related to the presence of PPS in patients with GAD. METHODS: This is a post hoc analysis of a cross-sectional study. Functioning, in the presence (overall pain score >30; Visual Analog Scale) or absence of PPS, was assessed using the Sheehan Disability Scale (SDS) in three groups of patients; 1) GAD and comorbid MDD (GAD+MDD+), 2) GAD without comorbid MDD (GAD+MDD-), 3) controls (GAD-MDD-). ANCOVA models were used. RESULTS: Of those patients with GAD+MDD+ (n = 559), 436 (78.0%) had PPS, compared with GAD+MDD- (249 of 422, 59%) and controls (95 of 336, 28.3%). Functioning worsened in both GAD groups in presence of PPS (SDS least squares mean total score: 16.1 vs. 9.8, p < 0.0001, GAD+MDD+; 14.3 vs. 8.2, p < 0.0001, GAD+MDD-). The presence of PPS was significantly associated with less productivity. CONCLUSIONS: Functional impairment related to the presence of PPS was relevant. Clinical implications should be considered.

Epidemiology and Economic Burden of Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus in Spain: A Systematic Review.

INTRODUCTION: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in people with type 2 diabetes mellitus (T2DM). The objectives of this systematic literature review were to identify and synthesize published data describing the epidemiology and mortality of CVD in the T2DM population and the associated economic burden. METHODS: We conducted a systematic review searching the PubMed and MEDES databases from 2009 to 2019 using predefined selection criteria. Peer-reviewed observational studies reporting primary or secondary data on CVD prevalence, incidence, mortality, resource use and costs in patients with T2DM in Spain, written in English and Spanish, were included. Data were tabulated and summarized descriptively. RESULTS: Of 706 articles identified, 52 were included in the review. Most studies were based on data from hospital discharge databases and registries. The reported prevalence of CVD among patients with T2DM ranged from 6.9 to 40.8%. The prevalence of coronary heart disease ranged from 4.7 to 37%, stroke from 3.5 to 19.6%, peripheral artery disease from 2.5 to 13.0%, and heart failure from 4.3 to 20.1%. In-hospital CVD mortality rates ranged from 5.6 to 10.8%. Direct costs due to CVD in hospitalized patients with T2DM were increased (> 50%) compared with patients without CVD. No studies analysed indirect costs of CVD in patients with T2DM. CONCLUSIONS: The burden of CVD among patients with T2DM, combined with the elevated costs of care, highlights the importance of early prevention as part of integrated management of the disease to improve clinical and economic outcomes.

Glucagon-Like Peptide 1 Receptor Agonists in Type 2 Diabetes Mellitus: Data from a Real-World Study in Spain.

INTRODUCTION: This study aimed to describe utilization patterns, persistence, resource utilization and costs in patients with type 2 diabetes mellitus initiating treatment with glucagon-like peptide 1 receptor agonists in routine clinical practice in Spain. METHODS: This retrospective study of medical records in the Big-Pac database identified adults starting treatment with once-weekly (QW) dulaglutide, exenatide-QW or once-daily liraglutide between 1 November 2015 and 30 June 2017. Patients were followed for up to 18 months from treatment initiation. Data on clinical characteristics of patients, treatment patterns, average daily dose and costs were obtained for the three cohorts. Persistence over the 18-month period was evaluated using Kaplan-Meier curves. All analyses were descriptive. RESULTS: A total of 1402 patients were included in this study (dulaglutide [n = 492], exenatide-QW [n = 438] or liraglutide [n = 472]); 52.8% were men, and the mean (SD) age was 62 (11) years, glycated haemoglobin (HbA1c) was 8.1% (1.2) and body mass index was 35.5 (3.2) kg/m2 at treatment initiation. Persistence at 18 months was 59.1% (95% confidence interval [CI] 54.8-63.4) for dulaglutide, 45.7% (95% CI 41.0-50.4) for exenatide-QW and 46.6% (95% CI 42.1-51.1) for liraglutide. The average (SD) dose was 1.2 (0.4) mg/week for dulaglutide, 1.9 (0.3) mg/week for exenatide-QW and 1.1 (0.3) mg/day for liraglutide. The average reduction in HbA1c levels at 1 year was - 0.68% for patients who initiated dulaglutide, - 0.54% for patients who initiated exenatide-QW and - 0.50% for patients who initiated liraglutide. The mean (SD) total annual health care costs were €4072 (1946) for dulaglutide, €4418 (2382) for exenatide-QW and €4382 (2389) for liraglutide. CONCLUSION: Results suggest that patients who started treatment with dulaglutide had higher persistence over 18 months, presented lower HbA1c levels at 12 months and incurred lower annual total healthcare costs than patients who initiated exenatide-QW or liraglutide.

Type 2 diabetes has a major impact on patients psychologically and socially, as well as on healthcare costs. The glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are drugs that help maintain blood sugar at healthy levels. They are often used as the first injectable drugs if oral treatments are no longer effective. This study aimed to analyse the use of GLP-1 RAs, and the costs involved, among patients with type 2 diabetes who started treatment with once-weekly dulaglutide, once-weekly exenatide or liraglutide in routine clinical practice in Spain. An electronic database of medical records was used to obtain data from 1402 patients who started treatment with these drugs and were followed for a 1.5-year period. Results of this study suggest that patients who were prescribed dulaglutide stayed on their treatment longer and could reduce their blood sugar levels more efficiently, and at a lower cost, than those who received once-weekly exenatide or liraglutide. These findings could be helpful to physicians prescribing these drugs when considering how to improve the management of type 2 diabetes.