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.

Effects of Chios mastic gum on cardiometabolic risk factors.

Chios mastic gum (CMG), the resin produced by the trunk of Pistachia lentiscus var Chia, has been used for culinary and medicinal purposes since antiquity. Despite the fact that Pistacia species are widely distributed throughout the Mediterranean basin and in the circum-Mediterranean regions, CMG is a distinctive resin of the mastic trees grown exclusively in the southern part of the island of Chios. CMG has been used for centuries as a spice, a cosmetic, but its most important usage has been as a strong phytotherapeutic therapy, primarily for the management of gastrointestinal diseases. Recently, there are studies demonstrating that CMG has hypolipidemic, cardioprotective and antidiabetic properties. Therefore, the aim of the present review is to summarize the existing literature data regarding the potential beneficial effects of CMG on cardio-metabolic risk factors.

Telemedicine and diabetes during the COVID-19 era.

The coronavirus disease 2019 (COVID-19) pandemic affected everyone's life and especially those with chronic conditions, such as diabetes. Therefore, the need for medical care in such populations resulted in identification of new models of health care avoiding physical consultation and reducing the risk of COVID-19 transmission, giving emphasis to telemedicine. There is an increasing amount of studies showing the beneficial impact of the use of telemedicine in patients with type 1 diabetes, while for patients with type 2 diabetes the existing data are limited and conflicting. Therefore, the aim of the present review is to summarize the existing literature data on the impact of telemedicine on the follow-up of patients with diabetes during the pandemic as well as its place in the management of patients with diabetes in the future.

Investigating Diabetes Mellittus Impact on Various Aspects of Patients' Quality of Life.

The aim of the study was to evaluate the quality of life (QoL) of patients with diabetes mellitus (DM) Methods: A cross-sectional study was conducted using the Audit of Diabetes-Depended Quality of Life (ADDQoL) questionnaire. The study included adult patients with diabetes mellitus type 1 (DM 1) or type 2 (DM 2). Results: A total of 253 patients were enrolled in the study. Despite the fact that the majority of participants stated a good QoL, DM has a negative impact on all 19 domains of ADDQoL. The greater negative impact referred to the domain "freedom to eat". There was no relation between overall score of QoL and age, gender or type of DM. On the contrary, we found statistically significant relation between age, gender, type of DM, presence of comorbidities and specific domains of Qol. Conclusions: Our findings, which are in accordance with the literature, highlight the great negative impact of DM on QoL of diabetics and they could be used by health professionals and policy makers to improve patients' well-being.

Investigating Diabetes Mellitus Patients' Experiences with Self Monitoring Blood Glucose Methods.

Diabetes mellitus (DM) is a common metabolic disease characterized by high blood glucose levels, and it is considered as a modern global threat. Glucose monitoring is an important component of modern therapy for diabetes mellitus. Self-monitoring blood glucose (SMBG) by finger pricking or flash glucose monitoring (FGM) allows individual planning of treatment. The aim of this study was to investigate patients' experiences with self-monitoring blood glucose methods. METHODS: A cross-sectional study was conducted using the Glucose Monitoring Experiences Questionnaire (GME-Q), consisted of 22 items with an overall score ranging from 1 to 5 (higher score indicates better experiences). The study included adult patients with diabetes mellitus type 1 (DM 1) or type 2 (DM 2). RESULTS: Out of 253 participants (mean age, 56.4 years), 65.6% were suffering from DM type 2 and 34.4% from DM type 1, whereas 48.6% were using SMBG and 49.8% FGM. The mean score of convenience and effectiveness were higher in the group of patients using FGM, while SMBG found to be more discreet. The results of the analysis suggested that there was no relation between gender and effectiveness, discreetness or convenience of the method used for glucose monitoring. Furthermore, participants with diabetes type 2 reported higher "convenient" and "discreetness" score than patients with diabetes type 1. The analysis also indicated that there was no relation between the age of the participants and the effectiveness, discreetness and convenience of any glucose monitoring method. CONCLUSIONS: Improved self-glucose monitoring experiences are an essential component to achieve effective management of patients suffering from both DM 1 and DM 2. More research should be conducted on the field of glucose monitoring experiences, related to the cost of the methods, the user's training and the ability to support insulin/diet calculations.

Role of dipeptidyl peptidase 4 inhibitors in the new era of antidiabetic treatment.

The last few years important changes have occurred in the field of diabetes treatment. The priority in the therapy of patients with diabetes is not glycemic control per se rather an overall management of risk factors, while individualization of glycemic target is suggested. Furthermore, regulatory authorities now require evidence of cardiovascular (CV) safety in order to approve new antidiabetic agents. The most novel drug classes, i.e., sodium-glucose transporter 2 inhibitors (SGLT2-i) and some glucagon-like peptide-1 receptor agonists (GLP-1 RA), have been demonstrated to reduce major adverse CV events and, thus, have a prominent position in the therapeutic algorithm of hyperglycemia. In this context, the role of previously used hypoglycemic agents, including dipeptidyl peptidase 4 (DPP-4) inhibitors, has been modified. DPP-4 inhibitors have a favorable safety profile, do not cause hypoglycemia or weight gain and do not require dose uptitration. Furthermore, they can be administered in patients with chronic kidney disease after dose modification and elderly patients with diabetes. Still, though, they have been undermined to a third line therapeutic choice as they have not been shown to reduce CV events as is the case with SGLT2-i and GLP-1 RA. Overall, DPP-4 inhibitors appear to have a place in the management of patients with diabetes as a safe class of oral glucose lowering agents with great experience in their use.

Aspirin in primary prevention of cardiovascular disease in diabetes.

It is well established that people with diabetes are at an increased risk of cardiovascular disease compared with those without diabetes. Although the protective role of aspirin in secondary prevention is well documented, its role in primary prevention of cardiovascular disease in people with diabetes, after the results of major clinical trials and meta-analyses, is unclear. The observed discrepancies might be explained in part in terms of the differences between the background cardiovascular risks, follow-up periods, age and gender of the study populations. Recently, the results of the ASCEND trial in people with diabetes documented the cardiovascular benefit of aspirin for primary prevention, but with an increased risk of bleeding that might outweigh the observed cardiovascular benefit. Therefore, current guidelines recommend its use for primary prevention in people with and without diabetes under specific circumstances. The purpose of the present review is to summarize the existing literature data regarding the place that aspirin has in primary prevention of cardiovascular disease in people with diabetes.

Ketone bodies and the heart.

Ketone bodies are low chain organic substances with four carbon atoms, with ß-hydroxybutyric acid and acetone being the main ketone bodies in blood circulation. Under physiological conditions their levels are low while during conditions of oxidative stress, such as exercise, fasting state and acute illness, ketone body levels are increased. Recent findings have shown that in patients with heart failure their plasma concentration is increased. There is a positive correlation between increased energy metabolism of myocardial cells and the levels of ß-hydroxybutyric acid and acetone. Furthermore, it has been hypothesized that the mild ketosis caused by sodium glucose cotransporter 2 inhibitors is one of the possible pathogenetic mechanisms explaining the significant cardiovascular and renal benefits observed in patients with type 2 diabetes treated with these agents. The aim of the present review is to summarize the role of ketone bodies in both normal and pathological conditions, such as heart failure.

Effects of Glucagon-like Peptide-1 Receptor Agonists and Sodium-glucose Cotransporter 2 Inhibitors on Cardiorenal and Metabolic Outcomes in People Without Diabetes.

During the last decade, the results of large-scale, randomized, clinical trials on newer antidiabetic agents, glucagon-like peptide-1 (GLP-1) receptor agonists and sodium glucose cotransporter type 2 (SGLT2) inhibitor, have been published showing promising findings on cardiovascular and renal outcomes. Besides improving glycemic control, GLP-1 receptor agonists have been shown to modify cardiovascular risk factors, such as insulin resistance, body weight, blood pressure (BP), and lipid profile. Additionally, SGLT2 inhibitors except for glycemic control have been shown to induce weight loss and decrease BP. However, there are limited data regarding their effect on patients without diabetes. Therefore, the aim of the present review is to summarize the existing literature data regarding the effects of newer antidiabetic therapies on patients without diabetes.

Diabetes and dementia - the two faces of Janus.

Patients with type 2 diabetes are at high risk for cognitive decline and dementia. Despite the limited data on the possible pathogenetic mechanisms, evidence suggests that cognitive decline, and thus dementia and Alzheimer's disease, might arise from a complex interplay between type 2 diabetes and the aging brain, including decreased insulin signalling and glucose metabolism, mitochondrial dysfunction, neuroinflammation, and vascular disease. Furthermore, there is increasing interest on the effects of antidiabetic agents on cognitive decline. There are many studies showing that antidiabetic agents might have beneficial effects on the brain, mainly through inhibition of oxidative stress, inflammation, and apoptosis. In addition, experimental studies on patients with diabetes and Alzheimer's disease have shown beneficial effects on synaptic plasticity, metabolism of amyloid-ß, and microtubule-associated protein tau. Therefore, in the present review, we discuss the effects of antidiabetic agents in relation to cognitive decline, and in particular dementia and Alzheimer's disease, in patients with type 2 diabetes.

The COVID-19 pandemic and diabetes mellitus.

COVID-19, a disease caused by a novel coronavirus, SARS-CoV-2, has reached the proportion of a pandemic and presents with either mild and moderate symptoms or in severe cases with acute respiratory distress syndrome, multiple organ dysfunction syndrome and even death. Older age, hypertension, cardiovascular disease, diabetes mellitus and obesity significantly increase morbidity and mortality in COVID-19 patients. In the present review we summarize the existing, and daily growing, data on the impact of COVID-19 infection on patients with diabetes, their antidiabetic therapy as well as the extra precautions, apart from good glucose control, they have to take in order not to contract the virus. Social distancing and strict hand hygiene are of great importance in order to help the global goal of eradication of the disease.

Twenty-year trends in the prescription costs of Type 2 diabetes: Real world data and empirical analysis in Greece.

AIMS: To estimate and compare the prescription costs for the management of patients with diabetes over a period of 20 years in Greece, based on real world data. METHODS: The records of outpatients with T2D, monitored at three diabetes centres, were examined in four cross-sections (1998, 2006, 2012, 2018). Prescribed medicines per patient, along with a set of clinical indicators were recorded. Annual costs of pharmaceutical treatment per patient were calculated by using each year's nominal retail prices, as well as by adjusting for 2018 price levels, in order to account for price differences over time. RESULTS: 4066 patients were included in the analysis. Prescription patterns indicate a quick uptake of the new classes of glucose-lowering drugs and a reduction in the proportional use of sulfonylurea and glitazone. Adjusting for 2018 prices, the average total annual prescription cost per patient was 381.54 Euros (s.d. 297.44) in 1998 and 1147.21 Euros (s.d. 814.39) in 2018. Glucose-lowering drug costs per patient increase from 1998 onwards, whereas the costs of antihypertensive, antiplatelet and lipid-lowering treatment declined gradually, especially after 2006. CONCLUSIONS: Per patient prescription costs for glucose-lowering drugs present a steep increase, in Greece over the last 20 years. Real-world evidence studies that compare this increase with the changes in patient outcomes are essential in order to examine whether a costs-vs-outcomes balance is optimal.

Profile and factors associated with glycaemic control of patients with type 2 diabetes in Greece: results from the diabetes registry.

BACKGROUND: Strict glycaemic control early in the treatment process has been shown to reduce the occurrence of micro- and macro- vascular complications of diabetes in the long-term. Thus, treatment guidelines advise early intensification of treatment to achieve glycaemic control goals. However, evidence in Greece suggests that, despite guideline recommendations, glycaemic control among patients with T2DM remains challenging. This study presents the demographic and clinical characteristics of patients with T2DM in Greece using data from an electronic registry designed specifically for this treatment category and investigates the factors that are independently associated with glycaemic control. METHODS: This is a multi-center, observational, cross-sectional study to investigate epidemiological and clinical factors affecting glycaemic control among patients with T2DM in Greece. Data was collected via a web-based disease registry, the Diabetes Registry, which operated from January 1st to December 31st, 2017. Five large specialized diabetes centers operating in Greek hospitals participated in the study. RESULTS: Data for 1141 patients were retrieved (aged 63.02 ± 12.65 years, 56.9% male). Glycaemic control (Hb1Ac < 7%) was not achieved in 57.1% of patients. Factors independently associated with poor glycaemic control were: family history of diabetes [OR: 1.53, 95% CI: 1.06-2.23], BMI score between 25 to 30 [OR: 2.08, 95% CI: 1.05-4.13] or over 30 [OR: 2.12, 95% CI 1.12-4.07], elevated LDL levels [OR: 1.53, 95% 1.06-2.21] and low HDL levels [OR: 2.12, 95% CI: 1.44-3.12]. Lastly, use of injectable antidiabetic agents (in monotherapy or in combination) was less likely to be associated with poor glycaemic control versus treatment with combination of oral and injectable agents [OR: 0.50, 95% CI: 0.24-1.01]. This association was found to be marginally statistically significant. CONCLUSION: Inadequate lipid control, family history of diabetes and presence of obesity (ΒΜΙ ≥ 30 kg/m2) were associated with poor glycaemic control among study sample, whereas use of injectable antidiabetic agents was less likely to be associated with poor glycaemic control. These findings indicate how complex optimal glycaemic control is, highlighting the need for tailored interventions in high-risk subpopulations with T2DM.

The influence of gene polymorphisms on postprandial triglyceride response after oral fat tolerance test meal in patients with diabetes mellitus.

AIMS: We evaluated the influence of CETP (rs5882 and rs708272), APOE (rs7412, rs429358) and LPL (rs328) gene polymorphisms on triglyceride (TG) response to oral fat tolerance test (OFTT) meal in patients with well-controlled type 2 diabetes mellitus (T2DM). METHODS: Fifty-one men underwent OFTT and according to postprandial TG response patients were divided into two subgroups (positive [TG ≥ 220 mg/dL, 31 patients] and negative [TG < 220 mg/dL, 20 patients]). All patients were genotyped, and study variants were detected using polymerase chain reaction (PCR) and restricted fragment length polymorphism (RFLP) analysis. RESULTS: Patients with genotype SS of LPL gene compared with genotype SX had more frequently positive response to OFTT (P = .04) and lower high-density lipoprotein cholesterol (HDL-C) concentration (P = .03). Patients with positive response to OFTT and genotype SS of LPL gene compared with genotype SX had lower AUC (area under the curve)-TG, 1744 (368) vs 1887 (807) mg/dL/h, respectively, P = .04. CETP and APOE gene polymorphisms had no influence on postprandial TG response to OFTT. CONCLUSIONS: In patients with well-controlled T2DM, LPL but not CETP and APOE gene polymorphisms influenced TG postprandial response. Particularly, S447 allele carriers of LPL gene presented more frequently positive postprandial TG response to OFTT compared with 447X allele carriers. No differences were found between allele carriers of patients with negative response to OFTT in any other studied gene polymorphism.

Anti-diabetic treatment leads to changes in gut microbiome.

Numerous micro-organisms naturally reside in the human body assuming a symbiotic, or, at times, even a dysbiotic relationship with the host. These microbial populations are referred to as the human microbiota. Host microbial populations are an important mediator of gastro-intestinal mucosal permeability, bile acid metabolism, short-chain fatty acids synthesis, fermentation of dietary polysaccharides and FXR/TGR5 signaling. Variations in the composition and function of gut microbiota have been observed in type 2 diabetes mellitus, insulin resistance and obesity, as well as in inflammatory bowel diseases. The microbial imbalance induced by such pathological processes is described as dysbiosis. In this review, we describe the pathophysiological links between type 2 diabetes mellitus and gut microbiota, explore the effect of anti-diabetic drugs on gut microbiota and suggest possible therapeutic targets.

Antidiabetic treatment on memory and spatial learning: From the pancreas to the neuron.

The detrimental effects of constant hyperglycemia on neural function have been quantitatively and qualitatively evaluated in the setting of diabetes mellitus. Some of the hallmark features of diabetic encephalopathy (DE) are impaired synaptic adaptation and diminished spatial learning capacity. Chronic and progressive cognitive dysfunction, perpetuated by several positive feedback mechanisms in diabetic subjects, facilitates the development of early-onset dementia and Alzheimer's disease. Despite the numerous clinical manifestations of DE having been described in detail and their pathophysiological substrate having been elucidated in both type 1 and type 2 diabetes mellitus, an effective therapeutic approach is yet to be proposed. Therefore, the aim of this review is to summarize the growing body of evidence concerning the effect of current antidiabetic treatment options on diabetic and non-DE.