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.

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.

Comparison of tumor markers and inflammatory biomarkers in chronic obstructive pulmonary disease (COPD) exacerbations.

OBJECTIVE: The aim of the present study was: (a) to measure levels of the tumor markers, Carcinoembryonic antigen (CEA), Cancer antigen 19-9 (CA19-9), Cancer antigen 125 (CA125), Neuron specific enolase (NSE) and Cytokeratin fragments 19 (CYFRA21-1); (b) to investigate any correlation between them and the inflammatory biomarkers C-reactive protein (CRP), Erythrocyte sedimentation rate (ESR) and white blood cells count (WBC), in patients with chronic obstructive pulmonary disease (COPD) exacerbation, who belong in groups of severity C and D, as classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD); (c) and finally, to compare these results in these two groups. MATERIAL AND METHODS: Fifty-two patients with COPD exacerbation [35 male/17 female, mean age (± SD) 68.3 ± 6.4 years] were the study subjects, and were classified in severity groups C (n = 27) and D (n = 25), based on the spirometric classification, the number of exacerbations in the preceding year and the assessment of their symptoms by GOLD. Results. CEA and CA125 were increased in group D. In group C, there was a significant correlation between CRP and CA125 (p = 0.05). In group D, there was a significant correlation between WBC and NSE (p = 0.02), between CRP and CA19-9 (p = 0.02) and NSE (p < 0.001), and between the ESR and NSE (p = 0.03). CA125 (p = 0.01) and CA19-9 (p = 0.01) were significantly higher in group D compared to group C. In contrast, there was no significant difference in two groups for NSE, CEA and CYFRA21-1. CONCLUSION: Certain tumor markers were increased and were associated with increased levels of inflammatory biomarkers and with the disease severity. Inflammation might have a key pathogenetic role linking the above tumor markers with the severity of COPD.

Management of type 2 diabetes and its prescription drug cost before and during the economic crisis in Greece: an observational study.

BACKGROUND: The aim of the present study is to examine the clinical indices related to cardiovascular risk management of Greek patients with type 2 diabetes, before and after the major economic crisis that emerged in the country. METHODS: In this retrospective database study, the medical records of patients with type 2 diabetes treated at three diabetes outpatient centers of the national health system during 2006 and 2012 were examined. Only patients with at least six months of follow-up prior to the recorded examination were included. The prescription cost was calculated in Euros per patient-year (€PY). RESULTS: A total of 1953 medical records (938 from 2006 and 1015 from 2012) were included. There were no significant differences in adjusted HbA1c, systolic blood pressure and HDL-C, while significant reductions were observed in LDL-C and triglycerides. In 2012, a higher proportion of patients were prescribed glucose-lowering, lipid-lowering and antihypertensive medications. Almost 4 out of 10 patients were prescribed the new incretin-based medications, while the use of older drugs, except for metformin, decreased. A significant increase in the adjusted glucose-lowering prescription cost (612.4 [586.5-638.2] €PY vs 390.7 [363.5-418.0]; p < 0.001) and total prescription cost (1306.7 [1264.6-1348.7] €PY vs 1122.3[1078.1-1166.5]; p < 0.001) was observed. The cost of antihypertensive prescriptions declined, while no difference was observed for lipid-lowering and antiplatelet agents. CONCLUSIONS: During the economic crisis, the cardiovascular risk indices of Greek patients with type 2 diabetes being followed in public outpatient diabetes clinics did not deteriorate and in the case of lipid profile improved. However, the total prescription cost increased, mainly due to the higher cost of glucose-lowering prescriptions.

Diabetes management in the era of artificial intelligence.

Artificial intelligence is growing quickly, and its application in the global diabetes pandemic has the potential to completely change the way this chronic illness is identified and treated. Machine learning methods have been used to construct algorithms supporting predictive models for the risk of getting diabetes or its complications. Social media and Internet forums also increase patient participation in diabetes care. Diabetes resource usage optimisation has benefited from technological improvements. As a lifestyle therapy intervention, digital therapies have made a name for themselves in the treatment of diabetes. Artificial intelligence will cause a paradigm shift in diabetes care, moving away from current methods and toward the creation of focused, data-driven precision treatment.

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.

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.

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.

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.

Prevalence of target organ damage in hypertensive subjects attending primary care: C.V.P.C. study (epidemiological cardio-vascular study in primary care).

BACKGROUND: Except for the established risk factors, presence of target organ damage has an important role in the treatment of hypertensive subjects. The aim of the present study was to estimate the prevalence of target organ damage in primary care subjects. METHODS: This multi-centre, cross-sectional survey of 115 primary care physicians recruited 1095 consecutive subjects with hypertension: 611 men (55.8%); and 484 women (44.2%). A detailed history for the presence of cardiovascular disease and a thorough clinical examination was performed to each subject. RESULTS: Of the total study population, 44.5% (n = 487) had target organ damage (33.0% had left ventricular hypertrophy, 21.8% increased carotid intima media thickness, 11.0% elevated plasma creatinine levels and 14.6% microalbuminuria). Target organ damage was more prevalent in males than in females (P = 0.05). In addition, males had more often increased carotid intima media thickness than females (P = 0.009). On the contrary, females had more often microalbuminuria (P = 0.06) than males. No differences were observed between the two genders regarding left ventricular hypertrophy (P = 0.35) and elevated plasma creatinine levels (P = 0.21). Logistic regression analysis showed associations between target organ damage and dyslipidemia (P < 0.001), presence of metabolic syndrome (P = 0.005), diabetes (P < 0.001) and coronary artery disease (P < 0.001). CONCLUSION: A significant proportion of hypertensive subjects in primary care had documented associated target organ damage, with left ventricular hypertrophy being the most prevalent target organ damage.

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.

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.

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.

The impact of metabolic syndrome on left ventricular myocardial performance.

BACKGROUND: Metabolic syndrome (MetS) is common and is associated with increased cardiovascular morbidity and mortality. Recent prospective studies suggested that MetS is associated with increased risk of heart failure. In the present cross-sectional study, we examined the association between left ventricular myocardial performance with MetS. MATERIALS AND METHODS: A total of 550 non-diabetic subjects, 275 without MetS and 275 with MetS, matched for gender, age and body mass index and free of clinically apparent macrovascular disease were studied. MetS was diagnosed using the NCEP-ATP III criteria. Left ventricular myocardial performance was assessed using the Tei index. RESULTS: Both men and women with MetS had higher values of the Tei index, indicating worse myocardial performance, in comparison with those without MetS (p < 0.001). Participants with a cluster of more components of the MetS had higher Tei index values than those with fewer components of the MetS. In addition, among normotensive subjects, those with MetS had significantly higher Tei index values than subjects without MetS. Multivariate linear regression analysis, after adjustment for age and body mass index, demonstrated that MetS status and from the individual components of the MetS, high fasting blood glucose levels, higher blood pressure, low high density lipoprotein levels and high waist circumference were associated with worse myocardial performance. CONCLUSION: MetS is associated with subclinical myocardial dysfunction in both men and women. Strategies to reduce the cardiovascular burden and the risk of heart failure associated with MetS should aim at prevention of the MetS and its related conditions.

Prevalence of HPV infection among Greek women attending a gynecological outpatient clinic.

BACKGROUND: Human papillomavirus (HPV) infection is a causative factor for cervical cancer. Early detection of high risk HPV types might help to identify women at high risk of cervical cancer. The aim of the present study was to examine the HPV prevalence and distribution in cervical smears in a sample of Greek women attending a gynecological outpatient clinic and to explore the determinants of the infection. METHODS: A total of 225 women were studied. All women underwent a regular gynecological control. 35 HPV types were studied; 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 56, 58, 59, 61, 62, 66, 68, 70, 71, 72, 73, 81, 82, 83, 84, 85 and 89. Also, basic demographic information, sociodemographic characteristics and sexual behavior were recorded. RESULTS: HPV was detected in 22.7% of the study population. The percentage of the newly diagnosed women with HPV infection was 17.3%. HPV-16 was the most common type detected (5.3%) followed by HPV-53 (4.9%). 66.2% of the study participants had a Pap test during the last year without any abnormalities. HPV infection was related positively with alcohol consumption (OR: 2.19, 95% CI: 1.04-4.63, P = 0.04) and number of sexual partners (OR: 2.16, 95% CI: 1.44-3.25, P < 0.001), and negatively with age (OR: 0.93, 95% CI: 0.87-0.99, P = 0.03), and monthly income (OR: 0.63, 95% CI: 0.44-0.89, P = 0.01). CONCLUSION: The prevalence of HPV in women attending an outpatient clinic is high. Number of sexual partners and alcohol consumption were the most significant risk factors for HPV infection, followed by young age and lower income.

Self-medication with antibiotics in rural population in Greece: a cross-sectional multicenter study.

BACKGROUND: Self-medication is an important driver of antimicrobial overuse as well as a worldwide problem. The aim of the present study was to estimate the use of antibiotics, without medical prescription, in a sample of rural population presenting in primary care in southern Greece. METHODS: The study included data from 1,139 randomly selected adults (545 men/594 women, mean age +/- SD: 56.2 +/- 19.8 years), who visited the 6 rural Health Centres of southern Greece, between November 2009 and January 2010. The eligible participants were sought out on a one-to-one basis and asked to answer an anonymous questionnaire. RESULTS: Use of antibiotics within the past 12 months was reported by 888 participants (77.9%). 508 individuals (44.6%) reported that they had received antibiotics without medical prescription at least one time. The major source of self-medication was the pharmacy without prescription (76.2%). The antibiotics most frequently used for self-medication were amoxicillin (18.3%), amoxicillin/clavulanic acid (15.4%), cefaclor (9.7%), cefuroxim (7.9%), cefprozil (4.7%) and ciprofloxacin (2.3%). Fever (41.2%), common cold (32.0%) and sore throat (20.6%) were the most frequent indications for the use of self-medicated antibiotics. CONCLUSION: In Greece, despite the open and rapid access to primary care services, it appears that a high proportion of rural adult population use antibiotics without medical prescription preferably for fever and common cold.

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.

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.