A Horse, a Jockey, and a Therapeutic Dilemma: Choosing the Best Option for a Patient with Diabetes and Coronary Artery Disease

Current guidelines for the management of hyperglycemia recommend the use of agents with proven cardiovascular (CV) benefit in patients with type 2 diabetes (T2D) and established CV disease. Although both glucagon-like peptide 1 receptor agonists (GLP-1 RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2i) have been shown to reduce the risk of major adverse CV events (MACE) in high-risk populations with T2D, the ideal choice between the two classes for people with coronary artery disease remains controversial. SGLT2i reduce CV risk primarily through hemodynamic effects and changes in energy metabolism, making them the first choice in cases where heart failure or chronic kidney disease predominates. On the other hand, GLP-1 RA exert powerful anti-atherogenic properties that are the main drivers of their cardioprotection, and seem to have a consistent benefit in the atherosclerotic components of MACE. However, most people with diabetes and CV disease could take advantage of the complementary effects of the two drug categories on glycemic control, body weight, and diabetic complications. Future mechanistic studies and clinical head-to-head trials are expected to shed more light on this intriguing clinical dilemma and provide clear guidance for daily practice. © 2022, The Author(s), under exclusive licence to Springer Nature Switzerland AG

Sodium-Glucose Co-transporter 2 Inhibitors Versus Metformin as the First-Line Treatment for Type 2 Diabetes: Is It Time for a Revolution?

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as a promising therapeutic option for hyperglycemia and its complications. However, metformin remains the first-line pharmacological treatment in most algorithms for type 2 diabetes (T2D). Although metformin is generally believed to exert positive effects on cardiovascular (CV) outcomes, relevant data are mainly observational and potentially overinterpreted. Yet, it exerts numerous pleiotropic actions that favorably affect metabolism and diabetes comorbidities. CV outcome trials have demonstrated cardiorenal protection with SGLT2i among people at high CV risk and mostly on concomitant metformin therapy. However, post hoc analyses of these trials suggest that the cardiorenal effects of gliflozins are independent of background treatment and consistent across the full spectrum of CV risk. Considering the importance of addressing hyperglycemia as a means of preventing diabetic complications and significant knowledge gaps, particularly regarding the cost-effectiveness of SGLT2i in drug-naïve populations with T2D, the position of metformin in the management of people with diabetes at low CV risk remains solid for the moment. On the other hand, available evidence—despite its limitations—suggests that specific groups of people with T2D, particularly those with heart failure and kidney disease, could probably benefit more from treatment with SGLT2i. This narrative mini-review aims to discuss whether current evidence justifies the use of SGLT2i as the first-line treatment for T2D. © 2021, Springer Science+Business Media, LLC, part of Springer Nature

Non-insulin agents for the management of gestational diabetes: lack of evidence versus lack of action

[No abstract available

Gestational diabetes mellitus and quality of life during the third trimester of pregnancy

Purpose: The primary aim of this study was to investigate the effect of gestational diabetes mellitus (GDM) on the quality of life (QoL) of pregnant women during the third trimester of pregnancy. The secondary aim was to compare the QoL of pregnant women with GDM according to their therapeutic approach. This is the first study of this kind conducted in Greece. Methods: A case-control study with 62 pregnant women (31 with GDM and 31 with uncomplicated pregnancy), during the third trimester of pregnancy. QoL and Health Related QoL were studied with the use of three questionnaires (EQ-5D-5L, WHOQOL-BREF and ADDQoL). Results: A decrease in the QoL was found in pregnant women with GDM compared with pregnant women with uncomplicated pregnancy (p < 0.05) regarding both social life and health scales. On the contrary, there was no difference in the QoL between pregnant women with GDM who followed different treatment approaches (diet or insulin). Conclusions: The diagnosis of GDM is associated with a reduction in the QoL of pregnant women during the third trimester of pregnancy, while the type of treatment does not seem to further affect it. More studies should be conducted so that the modifiers of this association can be clarified. © 2019, Springer Nature Switzerland AG

Therapeutic approaches for latent autoimmune diabetes in adults: One size does not fit all [成人隐匿性自身免疫性糖尿病的治疗方法:不能千篇一律]

Recent advances in the understanding of latent autoimmune diabetes in adults (LADA) pathophysiology make it increasingly evident that people with LADA comprise a heterogenous group of patients. This makes the establishment of a standard treatment algorithm challenging. On top of its glucose-lowering action, insulin may exert anti-inflammatory effects, rendering it an attractive therapeutic choice for a type of diabetes in which autoinflammation and beta cell insufficiency play major pathogenetic roles. However, there is growing evidence that other antidiabetic drugs, such as metformin, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, and thiazolidinediones, might have a role in optimizing glycemic control and preserving beta cell function in individuals with LADA, either alone or in combination with insulin. Although most of these drugs have been routinely used in the daily clinical setting for years, large prospective randomized trials are needed to assess whether they are capable of delaying progression to insulin dependence as well as their effects on diabetic complications. The aim of the present review is to discuss the current state and future perspectives of LADA therapy, emphasizing the need for individualized and patient-centered therapeutic approaches. © 2019 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Lt

The role of autoimmunity in the pathophysiology of type 2 diabetes: Looking at the other side of the moon

Efforts to unravel the pathophysiological mechanisms of type 2 diabetes (T2D) have been traditionally trapped into a metabolic perspective. However, T2D is a phenotypically and pathophysiologically heterogenous disorder, and the need for a tailored approach in its management is becoming increasingly evident. There is emerging evidence that irregular immune responses contribute to the development of hyperglycemia in T2D and, inversely, that insulin resistance is a component of the pathogenesis of autoimmune diabetes. Nevertheless, it has not yet been fully elucidated to what extent the presence of conventional autoimmune markers, such as autoantibodies, in subjects with T2D might affect the natural history of the disease and particularly each response to various treatments. The challenge for future research in the field is the discovery of novel genetic, molecular, or phenotypical indicators that would enable the characterization of specific subpopulations of people with T2D who would benefit most from the addition of immunomodulatory therapies to standard glucose-lowering treatment. This narrative review aims to discuss the plausible mechanisms through which the immune system might be implicated in the development of metabolic disturbances in T2D and obesity and explore a potential role of immunotherapy in the future management of the disorder and its complications. © 2021 World Obesity Federatio