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Abstract Background Approximately two-thirds of individuals presenting to emergency departments in Western Sydney have glucose dysregulation, accelerating their risk of cardiovascular disease (CVD). We evaluated the prevalence and management of type 2 diabetes (T2D) in cardiology inpatients in Western Sydney. A novel model of care between diabetes and cardiology specialist hospital teams (joint specialist case conferencing, JSCC) is described herein and aimed at aligning clinical services and upskilling both teams in the management of the cardiology inpatient with comorbid T2D. Methods Cardiology inpatients at Blacktown-Mount Druitt Hospital were audited during a 1-month period. Results 233 patients were included, mean age 64 ± 16 years, 60% were male, 27% overweight and 35% obese. Known T2D comprised 36% (n = 84), whereas 6% (n = 15) had a new diagnosis of T2D, of which none of the latter were referred for inpatient/outpatient diabetes review. Approximately, 27% (n = 23) and 7% (n = 6) of known diabetes patients suffered hyper- and hypoglycaemia, respectively, and 51% (n = 43) had sub-optimally controlled T2D (i.e. HbA1c > 7.0%); over half (51%, n = 51) had coronary artery disease. Only two patients were treated with an SGLT2 inhibitor and no patients were on glucagon like peptide-1 receptor analogues. The majority were managed with metformin (62%) and therapies with high hypoglycaemic potential (e.g., sulfonylureas (29%)) and in those patients treated with insulin, premixed insulin was used in the majority of cases (47%). Conclusions Undiagnosed T2D is prevalent and neglected in cardiology inpatients. Few patients with comorbid T2D and CVD were managed with therapies of proven cardiac and mortality benefit. Novel models of care may be beneficial in this high-risk group of patients and discussed herein is the establishment of the diabetes-cardiology JSCC service delivery model which has been established at our institution.

Abstract Introduction This observational study aimed to assess the effectiveness of lixisenatide as add on therapy to basal insulin in diabetic type 2 patients previously treated with different insulin regimes. Methods Patients with diabetes type 2, prescribed with lixisenatide and basal insulin were divided in three groups (premixed insulin, basal bolus insulin and basal oral therapy (BOT). Difference in mean change in HbA1c, body mass index, total insulin doses, fasting blood glucose (FPG) and prandial blood glucose (PPG) were assessed after 3–6-months of follow-up. Results The primary outcomes were assessed in 111 patients. Lixisenatide added to basal insulin, reduced HbA1c and body weight significantly in all three groups of patients (p

Objectives: Prader-Willi Syndrome (PWS) is characterised by hyperphagia often leading to obesity; a known risk factor for insulin resistance and type 2 (T2) diabetes. We present a prepubertal girl with PWS who developed diabetes. Case presentation: Our case was diagnosed with PWS in infancy following investigation for profound central hypotonia and feeding difficulties. She commenced growth hormone (GH) aged 8 years for short stature and treatment improved linear growth. At age 12 years, she presented with polydipsia, polyuria and vulvovaginitis. She was overweight (BMI SDS +1.43). Diabetes was diagnosed (Blood glucose = 24.2 mmol/L, HbA1c = 121 mmol/mol or 13.2%). She was not acidotic and had negative blood ketones. Autoantibodies typical of type 1 diabetes were negative. She was initially treated with basal bolus insulin regime. GH was discontinued 3 months later due to concerns regarding GH-induced insulin resistance. Off GH, insulin requirements reduced to zero, allowing Metformin monotherapy. However off GH, she reported significant lethargy with static growth and increased weight. Combinations of Metformin with differing insulin regimes did not improve glucose levels. Liraglutide (GLP-1 agonist) and Metformin did not improve glucose levels nor her weight. Liraglutide and Empaglifozin (SGLT-2 inhibitor) therapy used in combination were well tolerated and demonstrated rapid normalisation of blood glucose and improvement in her HbA1c to within target (48 mmol/mol) which was sustained after 6 months of treatment. Conclusions: Newer treatments for type 2 diabetes (e. g. GLP-1 agonists or SGLT-2 inhibitors) offer potential treatment options for those with diabetes and PWS when conventional treatments are ineffective. – DM (Diabetes mellitus) is a rare complication of Prader-Willi Syndrome (PWS) before puberty. – This case demonstrates the challenges of managing PWS and DM including negotiating growth hormone therapy and pubertal induction/augmentation. – Conventional therapies (e. g. oral hypoglycaemic agents and insulin) failed to achieve adequate glycaemic parameters. – Recently developed therapies of Liraglutide (GLP-1) and Empaglifozin (SGLT-2 inhibitor) used combination were well tolerated, led to rapid normalisation of blood glucose and a sustained improvement in HbA1c within target. – This is the first case report describing the use of a GLP-1 agonist and a SGLT-2 inhibitor used in combination in a child with PWS and DM. [ABSTRACT FROM AUTHOR]

Obesity and its comorbidities, including type 2 diabetes mellitus, cardiovascular disease, heart failure and non-alcoholic liver disease are a major health and economic burden with steadily increasing numbers worldwide. The need for effective pharmacological treatment options is strong, but, until recently, only few drugs have proven sufficient efficacy and safety. This article provides a comprehensive overview of obesity and its comorbidities, with a special focus on organ-specific pathomechanisms. Bariatric surgery as the so far most-effective therapeutic strategy, current pharmacological treatment options and future treatment strategies will be discussed. An increasing knowledge about the gut-brain axis and especially the identification and physiology of incretins unfolds a high number of potential drug candidates with impressive weight-reducing potential. Future multi-modal therapeutic concepts in obesity treatment may surpass the effectivity of bariatric surgery not only with regard to weight loss, but also to associated comorbidities. [ABSTRACT FROM AUTHOR]

Introduction: Adequate persistence to antidiabetic treatment is highly important to achieve proper glycemic control. In this study we evaluate the persistence to treatment with dipeptidyl peptidase-4 inhibitors, sodium-glucose co-transporter-2 inhibitors, and glucagon-like peptide-1 receptor agonists in a nationwide cohort of patients with type 2 diabetes.Methods: Using a central database in Hungary, we analyzed the persistence to the treatment with dipeptidyl peptidase-4 inhibitors (n = 59,900), sodium-glucose co-transporter-2 inhibitors (n = 26,052), and glucagon-like peptide-1 receptor agonists (n = 17,332) at treatment intensification between 2014 and 2016. We also compared the persistence of dipeptidyl peptidase-4 inhibitors (n = 9163) and sodium-glucose co-transporter-2 inhibitors (n = 1257) in initial therapy to that of metformin (n = 79,305) or sulfonylureas (n = 29,057). The rates of persistence to treatment and risk of non-persistence are reported.Results: The persistence rates of dipeptidyl peptidase-4 inhibitors, sodium-glucose co-transporter-2 inhibitors, and glucagon-like peptide-1 receptor agonists at treatment intensification were 69.6%, 67.8%, and 66.3% at year 1 which decreased to 57.3%, 56.8%, and 52.1% by year 2, respectively. The risk of non-persistence was higher by 6.6% (95% CI 3.6-9.6) for sodium-glucose co-transporter-2 inhibitors and by 8.3% (95% CI 5.0-11.5) for glucagon-like peptide-1 receptor agonists as compared to dipeptidyl peptidase-4 inhibitors. Novel oral antidiabetic drugs in fixed versus free add-on combinations with metformin had higher persistence. The persistence to treatment with novel oral antidiabetic drugs in initial therapy was better (dipeptidyl peptidase-4 inhibitors, 59.6% and 47.6%; sodium-glucose co-transporter-2 inhibitors, 61.9% and 47.0%) than that of initial monotherapy with metformin (47.0% and 39.1%) or sulfonylureas (52.4% and 41.8%) at years 1 and 2, respectively.Conclusion: Analysis of persistence of treatment with novel glucose-lowering medications revealed differences between drug classes, favoring dipeptidyl peptidase-4 inhibitors vs. sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists. Persistence data of novel antihyperglycemic agents may be useful for guiding the decision at initiation of antidiabetic treatment.Funding: Hungarian Diabetes Association.Plain Language Summary: Plain language summary available for this article. [ABSTRACT FROM AUTHOR]

The global epidemic of type 2 diabetes (T2DM) continues largely unabated due to an increasingly sedentary lifestyle and obesogenic environment. A cost-effective patient-centred approach, incorporating glucose-lowering therapy and modification of cardiovascular risk factors, could help prevent the inevitable development and progression of macrovascular and microvascular complications. Glycaemic optimization requires patient structured education, self-management and empowerment, and psychological support along with early and proactive use of glucose lowering therapies, which should be delivered in a system of care as shown by the Chronic Care Model. From diagnosis, intensive glycaemic control and individualised care is aimed at reducing complications. In older people, the goal is maintaining quality of life and minimizing morbidity, especially as overtreatment increases hypoglycaemia risk. Maintaining durable glycaemic control is challenging and complex to achieve without hypoglycaemia, weight gain and other significant adverse effects. Overcoming patient and physician barriers can help ensure adequate treatment initiation and intensification. Cardiovascular safety studies with newer glucose-lowering agents are now mandatory, with a sodium glucose co-transporter-2 inhibitor (empagliflozin), and two glucagon like peptide-1 receptor agonists (liraglutide and semaglutide) being the first to demonstrate superior CV outcomes compared with placebo. [ABSTRACT FROM AUTHOR]

Background/objective: Signals from the FDA Adverse Event Reporting System (AERS) and pre-clinical and human pancreata obtained from organ donors have suggested that incretin-based therapies used to treat type 2 diabetes mellitus, such as glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, may increase the risk of acute pancreatitis (AP) and pancreatic cancer (PC). However, data from observational studies and randomized trials have been conflicting. We conducted a literature review to identify and summarize all observational data published assessing the pancreatic safety of incretins. Methods: Searches were conducted in MEDLINE via PubMed and Embase using the key terms for the time period of 1 January 2005, to 12 February 2014. A total of 180 articles were screened in abstract form and 49 were subsequently reviewed in full text for inclusion. Data from 12 articles are included in this report. Findings: Data from the FDA AERS database suggest increased risk of AP and PC with GLP-1 receptor agonist and DPP-4 inhibitor use. These findings are not supported by population-based observational studies for either AP or PC; however, studies assessing the relationship between PC and incretin-based therapies are limited. Conclusions: Current evidence is conflicting and inadequate to conclude whether use of incretin-based therapies increases the risk of AP and PC. Further studies, with the ability to provide long term follow-up, are needed. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus is a chronic progressive disease, and over time patients often need to be treated with more than one type of antidiabetic agent in order to maintain control of blood glucose levels. Dipeptidyl peptidase-4 inhibitors are one of the newer classes of antidiabetic drugs used in the treatment of diabetes. These oral incretin-based therapies are effective at improving glycemic control, have a low risk of hypoglycemia, are weight neutral, and can be administered in combination with other antidiabetic agents. This article summarizes the pharmacological and pharmacokinetic properties of alogliptin, a dipeptidyl peptidase-4 inhibitor, and also evaluates its clinical efficacy, safety and tolerability in the treatment of patients with Type 2 diabetes. [ABSTRACT FROM AUTHOR]

Introduction: 'Incretin-based' therapies, such as the glucagon-like peptide-1 (GLP-1) receptor agonists, represent a major advance in type 2 diabetes mellitus (T2DM) treatment. GLP-1 receptor agonists differ substantially in their duration of action, frequency of administration and clinical profile. Methods: This article reviews the mechanisms of action and clinical evidence for GLP-1 receptor targeting and discusses differences between GLP-1 therapies, focusing particularly on clinical data for the GLP-1 receptor agonist, lixisenatide. Results: GLP-1 therapies target islet cell 'defects' of insufficient insulin and excessive glucagon secretion in T2DM, in a glucose-dependent manner, with minimal risk of hypoglycemia. Different GLP-1 therapies exert differential effects on fasting and postprandial glycemia (both being major determinants of glycemic control). They also slow gastric emptying to different extents, probably accounting for different effects to reduce postprandial glycemia. The GetGoal phase 3 studies in T2DM have confirmed the efficacy of once-daily lixisenatide in reducing plasma glucose and glycated hemoglobin (HbA), with a pronounced lowering of postprandial plasma glucose (PPG), as monotherapy and as add-on to oral antidiabetic drugs and to basal insulin. Lixisenatide's ability to diminish PPG is probably partly mediated by its marked ability to delay gastric emptying. Lixisenatide is generally well tolerated, with possibly better gastrointestinal tolerability and lower risk of hypoglycemia than exenatide immediate release. Lixisenatide is associated with a beneficial effect on weight, with either no change or a decrease in body weight when administered as add-on therapy to basal insulin in overweight patients with T2DM. Conclusions: Lixisenatide improves glycemic control, by primarily affecting PPG, while preventing weight gain or reducing body weight with a low risk of hypoglycemia in T2DM. Lixisenatide is likely to represent a significant advance in the management of T2DM, perhaps particularly in those patients with relatively faster gastric emptying and lower levels of HbA, including those receiving basal insulin. [ABSTRACT FROM AUTHOR]

Abstract: Background: Increased understanding of the role of incretin hormones in maintaining glucose homeostasis has enabled the development of pharmacotherapies that target deficient incretin activity in type 2 diabetes mellitus (T2DM). Incretin therapies are premised on 1 of 2 approaches: (1) augmenting the activity of the hormone glucagon-like peptide (GLP)-1 (GLP-1 receptor agonists) and (2) inhibiting the degradation of GLP-1 by dipeptidyl peptidase (DPP)-4 (DPP-4 inhibitors). Objective: This review discusses the pharmacokinetic properties and clinical profiles of the GLP-1 receptor agonists (exenatide twice daily, liraglutide once daily, exenatide once weekly, taspoglutide, and albiglutide) and the DPP-4 inhibitors (sitagliptin, saxagliptin, vildagliptin, and alogliptin) available for use or in late-stage development. Methods: A search of PubMed for literature published between 2000 and mid-2010 was conducted using the names of each agent as key words. Phase III and IV studies were included in the review of efficacy and tolerability. Supplemental searches of abstracts from major diabetes conferences provided additional information on pharmacokinetic properties. Searches of all reference lists were performed to identify additional references of interest. Results: The PubMed search identified multiple randomized, controlled clinical studies of the GLP-1 receptor agonists and the DPP-4 inhibitors administered as monotherapy or in combination regimens. Reductions from baseline in glycosylated hemoglobin ranged from 0.4% to 1.5% with exenatide 5 to 10 μg/d (7 studies), 0.6% to 1.5% with liraglutide 0.6 to 1.8 mg/d (6 studies), 0.3% to 1.0% with sitagliptin 25 to 200 mg/d (9 studies), 0.5% to 0.9% with saxagliptin 2.5 to 10 mg/d (3 studies), 0.4% to 1.0% with vildagliptin 50 to 100 mg/d (6 studies), and 0.4% to 0.8% with alogliptin 12.5 to 25 mg/d (4 studies). Dosage adjustments and caution in prescribing incretin therapies are recommended in patients with renal disease, with those recommendations varying based on the agent and the degree of dysfunction. Incretin therapies have been associated with few interactions with commonly used antihyperglycemic and cardiovascular therapies. Conclusion: Based on the pharmacokinetic and therapeutic characteristics described in previously published Phase III and IV studies of incretin therapies, these agents may provide an option for the management of T2DM. [Copyright &y& Elsevier]

Type 2 diabetes (T2D) is a serious and increasing problem in the UK. Large numbers of people are suffering from the disease, and its onset is occurring at younger ages, requiring prolonged treatment. Current therapies pose challenges for patients and health professionals, and new methods of treatment are therefore needed. This article examines a group of treatments--the incretin therapies--which have recently become available. It considers the clinical evidence for these therapies relevant to UK-based prescribing, and their potential benefits for patients with T2D. Awareness of these therapies, the evidence supporting them, and the clinical recommendations for their use will allow diabetes nurses to expand treatment options for patients with T2D. [ABSTRACT FROM AUTHOR]

The incretin effect, mediated by glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), plays an important role in the regulation of insulin secretion in response to oral glucose. The discovery of deficiencies in incretin pathways associated with development of type 2 diabetes mellitus has propelled the growth of incretin-based therapies in patients with this disease. The basic rationale for incretin-based therapies, including both GLP-l-receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors is reviewed, focusing on their roles in glucose regulation and potential therapeutic benefits. Increased awareness of the differences among incretin mimetics, GLP-1 analogs, and DPP-4 inhibitors, including their structures, half-lives, dosages, hemoglobin A1c-lowering capacities, effects on weight, and adverse events will help shape the future of these therapeutic agents. Improved understanding of the mechanism of action and clinical effects of incretin-based therapies will help advance their appropriate use within clinical practice. [ABSTRACT FROM AUTHOR]

Background: Approximately two-thirds of individuals presenting to emergency departments in Western Sydney have glucose dysregulation, accelerating their risk of cardiovascular disease (CVD). We evaluated the prevalence and management of type 2 diabetes (T2D) in cardiology inpatients in Western Sydney. A novel model of care between diabetes and cardiology specialist hospital teams (joint specialist case conferencing, JSCC) is described herein and aimed at aligning clinical services and upskilling both teams in the management of the cardiology inpatient with comorbid T2D. Methods: Cardiology inpatients at Blacktown-Mount Druitt Hospital were audited during a 1-month period. Results: 233 patients were included, mean age 64 ± 16 years, 60% were male, 27% overweight and 35% obese. Known T2D comprised 36% (n = 84), whereas 6% (n = 15) had a new diagnosis of T2D, of which none of the latter were referred for inpatient/outpatient diabetes review. Approximately, 27% (n = 23) and 7% (n = 6) of known diabetes patients suffered hyper- and hypoglycaemia, respectively, and 51% (n = 43) had sub-optimally controlled T2D (i.e. HbA1c > 7.0%); over half (51%, n = 51) had coronary artery disease. Only two patients were treated with an SGLT2 inhibitor and no patients were on glucagon like peptide-1 receptor analogues. The majority were managed with metformin (62%) and therapies with high hypoglycaemic potential (e.g., sulfonylureas (29%)) and in those patients treated with insulin, premixed insulin was used in the majority of cases (47%). Conclusions: Undiagnosed T2D is prevalent and neglected in cardiology inpatients. Few patients with comorbid T2D and CVD were managed with therapies of proven cardiac and mortality benefit. Novel models of care may be beneficial in this high-risk group of patients and discussed herein is the establishment of the diabetes-cardiology JSCC service delivery model which has been established at our institution. [ABSTRACT FROM AUTHOR]

Introduction: This observational study aimed to assess the effectiveness of lixisenatide as add on therapy to basal insulin in diabetic type 2 patients previously treated with different insulin regimes. Methods: Patients with diabetes type 2, prescribed with lixisenatide and basal insulin were divided in three groups (premixed insulin, basal bolus insulin and basal oral therapy (BOT). Difference in mean change in HbA1c, body mass index, total insulin doses, fasting blood glucose (FPG) and prandial blood glucose (PPG) were assessed after 3–6-months of follow-up. Results: The primary outcomes were assessed in 111 patients. Lixisenatide added to basal insulin, reduced HbA1c and body weight significantly in all three groups of patients (p < 0.001 for all), with the most prominent reduction in the basal bolus group of patients which had the highest baseline HbA1c compared to premix and BOT treatment groups. Regarding a difference in total insulin dose the reduction was statistically significant in the basal bolus (p = 0.006) and premix group (p < 0.001). FPG and PPG were also significantly reduced over time in all three groups (p < 0.001 for all). A composite outcome (reduction of HbA1c below 7% (53 mmol/mol) with any weight loss) was achieved in 27% of total patients included in the study, reduction of HbA1c below 7% was observed in 30% of patients, while 90% of patients experienced weight reduction. Conclusion: These results indicate that lixisenatide add on basal insulin treatment (BIT) can improve glycemic control in a population with long-standing type 2 diabetes and previously uncontrolled on other insulin therapy. [ABSTRACT FROM AUTHOR]