Titratable fixed-ratio combination of insulin glargine plus lixisenatide: A simplified approach to glycemic control in type 2 diabetes mellitus.

Abstract Approximately 50% of patients with type 2 diabetes mellitus (T2DM) do not achieve glycemic targets and require treatment intensification. A fixed-ratio combination of a glucagon-like peptide-1 receptor agonist (GLP-1 RA) with basal insulin, such as lixisenatide with insulin glargine (iGlarLixi), exploits the complementary mechanisms of action of each component to address hyperglycemia while mitigating potential adverse events (AEs). The iGlarLixi dose is titrated considering the effect of basal insulin on fasting plasma glucose, and the fixed-ratio combination ensures that the lixisenatide dose never exceeds 20 μg/day. We describe the characteristics of iGlarLixi therapy, based on the LixiLan clinical program, and provide guidance on the characteristics of patients likely to benefit from such treatment in routine clinical practice. In the phase III LixiLan trials, iGlarLixi resulted in significantly greater reductions in glycated hemoglobin (HbA1c), better achievement of HbA1c targets, less glycemic variability versus insulin glargine, lixisenatide or GLP-1 RA alone, and was associated with weight control, less hypoglycemia versus insulin glargine, and fewer GI AEs versus lixisenatide. Findings were consistent regardless of age, diabetes duration, and baseline HbA1c. The efficacy, safety, and convenient once-daily administration schedule of iGlarLixi make it a valuable treatment option for patients with T2DM requiring treatment intensification

Glucose control and vascular outcomes in type 2 diabetes: Is the picture clear?

The overall impact of glucose lowering on vascular complications and major clinical outcomes, including mortality, in type 2 diabetes is still an open issue. While intensive glucose control has undoubted benefit for microvascular end points, the relationship between glucose-lowering approaches and reduced incidence and/or progression of macrovascular complications is less clear. This review article will discuss the effect of glucose lowering per se as well as the effects of specific glucose-lowering therapies on vascular outcomes in type 2 diabetes. The role of lifestyle changes on cardiovascular outcomes will be also addressed. Recent analyses from large cardiovascular outcome studies (ACCORD, ADVANCE, and VADT) provide new information on factors that modulate the impact of intensive glucose lowering on outcomes, helping to identify the specific clinical characteristics of the patients receiving the intervention that would show a better response.While several studies on cardiovascular outcomes with diabetes drugs are available, they do not clearly highlight a benefit from using a specific medication or will require additional evidence, as for the sodium-glucose cotransporter 2 blockers

Cross-Talk between PPARγ and Insulin Signaling and Modulation of Insulin Sensitivity

PPARγ activation in type 2 diabetic patients results in a marked improvement in insulin and glucose parameters, resulting from an improvement of whole-body insulin sensitivity. Adipose tissue is the major mediator of PPARγ action on insulin sensitivity. PPARγ activation in mature adipocytes induces the expression of a number of genes involved in the insulin signaling cascade, thereby improving insulin sensitivity. PPARγ is the master regulator of adipogenesis, thereby stimulating the production of small insulin-sensitive adipocytes. In addition to its importance in adipogenesis, PPARγ plays an important role in regulating lipid, metabolism in mature adipocytes by increasing fatty acid trapping. Finally, adipose tissue produces several cytokines that regulate energy homeostasis, lipid and glucose metabolism. Disturbances in the production of these factors may contribute to metabolic abnormalities, and PPARγ activation is also associated with beneficial effects on expression and secretion of a whole range of cytokines

Gestione iniziale della terapia con insulina basale nel paziente diabetico

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GnRH agonist versus GnRH antagonist in in vitro fertilization and embryo transfer (IVF/ET)

Several protocols are actually available for in Vitro Fertilization and Embryo Transfer. The review summarizes the main differences and the clinic characteristics of the protocols in use with GnRH agonists and GnRH antagonists by emphasizing the major outcomes and hormonal changes associated with each protocol. The majority of randomized clinical trials clearly shows that in "in Vitro" Fertilization and Embryo Transfer, the combination of exogenous Gonadotropin plus a Gonadotropin Releasing Hormone (GnRH) agonist, which is able to suppress pituitary FSH and LH secretion, is associated with increased pregnancy rate as compared with the use of gonadotropins without a GnRH agonist. Protocols with GnRH antagonists are effective in preventing a premature rise of LH and induce a shorter and more cost-effective ovarian stimulation compared to the long agonist protocol. However, a different synchronization of follicular recruitment and growth occurs with GnRH agonists than with GnRH antagonists. Future developments have to be focused on timing of the administration of GnRH antagonists, by giving a great attention to new strategies of stimulation in patients in which radio-chemotherapy cycles are needed

Gut: A key player in the pathogenesis of type 2 diabetes?

The gut regulates glucose and energy homeostasis; thus, the presence of ingested nutrients into the gut activates sensing mechanisms that affect both glucose homeostasis and regulate food intake. Increasing evidence suggest that gut may also play a key role in the pathogenesis of type 2 diabetes which may be related to both the intestinal microbiological profile and patterns of gut hormones secretion. Intestinal microbiota includes trillions of microorganisms but its composition and function may be adversely affected in type 2 diabetes. The intestinal microbiota may be responsible of the secretion of molecules that may impair insulin secretion/action. At the same time, intestinal milieu regulates the secretion of hormones such as GLP-1, GIP, ghrelin, gastrin, somatostatin, CCK, serotonin, peptide YY, GLP-2, all of which importantly influence metabolism in general and in particular glucose metabolism. Thus, the aim of this paper is to review the current evidence on the role of the gut in the pathogenesis of type 2 diabetes, taking into account both hormonal and microbiological aspects

Report from the CVOT Summit 2020:new cardiovascular and renal outcomes

The 6th Cardiovascular Outcome Trial (CVOT) Summit "Cardiovascular and Renal Outcomes 2020" was the first to be held virtually on October 29-30, 2020. As in previous years, this summit served as reference meeting for in-depth discussions on the topic of recently completed and presented major outcome trials. This year, focus was placed on the outcomes of VERTIS-CV, EMPEROR-Reduced, DAPA- CKD, and FIDELIO-DKD. Trial implications for diabetes management and the impact on new treatment algorithms were highlighted for diabetologists, cardiologists, endocrinologists, nephrologists, and general practitioners. Discussion evolved from major outcome trials using SGLT-2 inhibitors for treatment and prevention of heart failure and chronic kidney disease in people with and without diabetes, to additional therapy options for chronic kidney disease with a novel mineralocorticoid receptor antagonist. Furthermore, challenges in diabetes management like COVID-19 and obesity, as well as novel treatment strategies and guidelines, were discussed. The 7th Cardiovascular Outcome Trial Summit will be held virtually on November, 18-19, 2021 (http://www.cvot.org)

Patient-reported outcomes in elderly patients with type 2 diabetes mellitus treated with dual oral therapy: a multicenter, observational study from Italy

Objective: To assess patient-reported outcomes after two years of use of dual oral anti-diabetes drug (OAD) therapy in elderly people (≥65 years) with type 2 diabetes mellitus (T2DM) from Italy under real-life settings. Methods: 3-AGE was a prospective, non-interventional study in elderly people with T2DM inadequately controlled on metformin monotherapy (defined as glycated hemoglobin [HbA1c] 7.0–9.0%), in whom a second OAD was prescribed. Primary endpoint was to assess the physical and psychological symptoms associated with T2DM from baseline to 24 months using the Diabetes Symptom Check List revised (DSC-R) questionnaire. Patient's quality of life and health status, treatment satisfaction, consumption of healthcare resources, and physician satisfaction with treatment were also assessed (secondary endpoints) using validated questionnaires. Additionally, safety and clinical characteristics were also evaluated. Results: The mean age of the study population (N = 860) was 71.5 ± 5.2 years. Addition of a second OAD significantly (p p p Conclusion: Addition of a second OAD improved physical and psychological symptoms associated with T2DM and was well tolerated in elderly people under real-life settings