Impact of Sodium-Glucose Cotransporter 2 Inhibitors on Cardiovascular and Renal Outcomes in Heart Failure Patients With Type 2 Diabetes: A Literature Review.

The management of heart failure (HF) in patients with type 2 diabetes has significantly evolved with the introduction of sodium-glucose cotransporter 2 (SGLT2) inhibitors. This article aims to consolidate existing knowledge on the efficacy of these inhibitors in managing HF in this patient population. Major medical databases, including PubMed, Scopus, and Web of Science, were reviewed, prioritizing research from the last decade. The results of this review highlight the mechanisms of action of SGLT2 inhibitors, their clinical benefits, challenges in patient management, and outcomes associated with their use. These medications were found to not only improve glycemic control but also offer significant cardiovascular and renal benefits, reducing cardiovascular mortality and major adverse cardiovascular events. However, challenges and knowledge gaps persist, particularly regarding long-term effects and safety in diverse populations. The conclusions of this review underscore the importance of updating clinical guidelines to incorporate these findings and propose the need for future research to address existing gaps and optimize the use of SGLT2 inhibitors in clinical practice.

Management of male obesity-related secondary hypogonadism: A clinical update.

The global obesity pandemic has resulted in a rise in the prevalence of male obesity-related secondary hypogonadism (MOSH) with emerging evidence on the role of testosterone therapy. We aim to provide an updated and practical approach towards its management. We did a comprehensive literature search across MEDLINE (via PubMed), Scopus, and Google Scholar databases using the keywords "MOSH" OR "Obesity-related hypogonadism" OR "Testosterone replacement therapy" OR "Selective estrogen receptor modulator" OR "SERM" OR "Guidelines on male hypogonadism" as well as a manual search of references within the articles. A narrative review based on available evidence, recommendations and their practical implications was done. Although weight loss is the ideal therapeutic strategy for patients with MOSH, achievement of significant weight reduction is usually difficult with lifestyle changes alone in real-world practice. Therefore, androgen administration is often necessary in the management of hypogonadism in patients with MOSH which also improves many other comorbidities related to obesity. However, there is conflicting evidence for the appropriate use of testosterone replacement therapy (TRT), and it can also be associated with complications. This evidence-based review updates the available evidence including the very recently published results of the TRAVERSE trial and provides comprehensive clinical practice pearls for the management of patients with MOSH. Before starting testosterone replacement in functional hypogonadism of obesity, it would be desirable to initiate lifestyle modification to ensure weight reduction. TRT should be coupled with the management of other comorbidities related to obesity in MOSH patients. Balancing the risks and benefits of TRT should be considered in every patient before and during long-term management.

The Cardiovascular Benefits of Glucagon-Like Peptide-1 Receptor Agonists as Novel Diabetes Drugs Are Mediated via the Suppression of miR-203a-3p and miR-429 Expression.

Coronary artery disease (CAD) is associated with a high fatality rate and a heavy global health care burden. Glucagon-like peptide-1 (GLP-1) exerts positive cardiovascular effects, although the molecular mechanisms are unclear. Therefore, this study aimed to verify whether the cardioprotective effects of GLP-1 are mediated through the regulation of micro-RNA (miRNA) expression. Follow-up assessments were conducted for 116 patients with type 2 diabetes mellitus (T2DM) alone (controls) and 123 patients with both T2DM and CAD. After matching, each group comprised 63 patients, and age, body mass index, and serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglycerides (TG), and hemoglobin A1C (HbA1c) were compared. Subsequently, the expression profiles of four circulating miRNAs (miR-203a-3p, miR-429, miR-205-5p, and miR-203b-5p) were assessed via quantitative reverse transcription real-time polymerase chain reaction in the 63 patients with diabetes and CAD between 6 months (baseline) and 12 months after the initiation of GLP-1 receptor (GLP-1R) therapy. As expected, the metabolic factors were significantly improved after 6 months of treatment with GLP-1R compared with pre-treatment values, and the expression levels of two of the miRNAs (miR-203a-3p and miR-429) decreased from baseline levels in those with diabetes and CAD. The results suggest that the cardiovascular benefits induced by GLP-1R are mediated via suppressed expression of two miRNAs: miR-203a-3p and miR-429.

Pharmacodynamic and pharmacokinetic profiles of a novel GLP-1 receptor biased agonist-SAL0112.

BACKGROUND AND PURPOSE: GLP-1 receptor agonists are clinically utilized for type 2 diabetes and obesity. In vitro and in vivo preclinical studies were performed to assess the druggability of a novel small molecule GLP-1 receptor biased agonist SAL0112. EXPERIMENTAL APPROACH: The HTRF assay, FLIPR assay, TR-FRET assay, and PathHunter assay were utilized for in vitro studies. Liver transporter tests were conducted using the HEK293-OATP1B1 and HEK293-OATP1B3 cell lines. In vitro stability assessments of various species and in vivo PK studies in rodents were performed. A model of type 2 diabetes and obesity induced by a high-energy diet in transgenic C57BL/6 mice expressing the human GLP-1 receptor gene was conducted. PRINCIPAL RESULTS: SAL0112 demonstrated high potency and selectivity in activating the Gαs pathway of the GLP-1 receptor, with no observed desensitization. SAL0112 demonstrated greater stability in human and rat liver microsomes compared to Danuglipron. In vivo PK studies revealed higher absorption of SAL0112 in rats. SAL0112 displayed a significantly lower potential for DDI on liver transporters compared to Danuglipron. SAL0112 led to significant reductions in body weight (P<0.001), blood glucose levels in OGTT (P<0.001), HbA1c (P<0.05) and improved insulin resistance (P<0.01). Notably, it increased peripheral adipocyte density and resolved hepatic steatosis. The efficacy of SAL0112 was found to be comparable to that of Danuglipron and Liraglutide. CONCLUSION: SAL0112 demonstrated potent and selective GLP-1 receptor biased agonism, effectively alleviating signs of type 2 diabetes in a mouse model. These promising findings pave the way for the advancement of SAL0112 into clinical trials.

Cardiovascular benefits of resistance exercise: It's time to prescribe.

Despite the well-known health benefits of regular physical activity, sedentary behavior and physical inactivity remain a real global pandemic. Exercise is associated with increased life expectancy, improved quality of life and prevention of multiple diseases. Although less implemented in practice compared to aerobic exercise, recent evidence shows that resistance exercise (RE) is also responsible for various benefits, including improvements in body composition, control of several cardiovascular (CV) risk factors, and reduction of CV outcomes. RE increases strength and muscle mass, is effective in controlling type 2 diabetes, and improves the management of obesity, lipids, and blood pressure profiles. In this setting, clinical guidelines recommend the inclusion of RE for primary and secondary CV risk prevention, particularly in combination with aerobic exercise, in which the benefits are most pronounced. Prescription of RE should follow a methodology that includes key variables such as frequency, intensity, type, time, and progression. Despite challenges, professionals in the CV field should be familiar with RE prescription in order to maximize its referral in clinical practice. This review aims to analyze the CV effects of RE and current recommendations regarding the prescription of this type of exercise.

Evolution of LDL-C lowering medications and their cardiovascular benefits: Past, present, and future.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Hyperlipidemia, particularly elevated low-density lipoprotein cholesterol (LDL-C) is one of the major risk factors for CVD. Major landmark cardiovascular outcome clinical trials demonstrated that LDL-C lowering medications reduce cardiovascular events, and the lower the LDL-C the better the outcome. This article discusses the evolution of LDL-C lowering medications starting from bile acid sequestrants (BAS), statin therapy, bempedoic acid, the proprotein convertase subtilisin kexin 9 (PCSK9) synthesis inhibitor, novel small interfering RNA-based therapy (inclisiran) to the most recent oral PCSK9 inhibitors (MK-0616) which is currently under phase 3 clinical trial studies.

Examination of Hibiscus sabdariffa's bioactive arsenal: pharmacological prospects and comprehensive insights into catalysing health and wellness through its therapeutic attributes-an exposition.

This study signifies the rich pharmacological potential of Hibiscus sabdariffa, exploring its bioactive components and their therapeutic implications for health and wellness. Despite the promising insights, a comprehensive critical analysis is essential to ensure scientific rigour. To address this, the study establishes clear aims and objectives, aiming to scrutinise the study findings through a meticulous assessment. In conclusion, this study, upon addressing these key points, aspires to offer a robust contribution to scientific research, by advancing the understanding of H. sabdariffa's therapeutic attributes and promoting the adoption of sustainable methodologies in scientific research.

Cardiovascular benefits and safety of sotagliflozin in type 2 diabetes mellitus patients with heart failure or cardiovascular risk factors: a bayesian network meta-analysis.

Background: As an antidiabetic agent, sotagliflozin was recently approved for heart failure (HF). However, its cardiovascular benefits in type 2 diabetic mellitus (T2DM) patients with HF or cardiovascular (CV) risk factors have not been systematically evaluated. The aim of this study is to evaluate the cardiovascular benefits and safety of sotagliflozin in T2DM patients with HF or CV risk factors using Bayesian network meta-analysis. Methods: Data were retrieved from PubMed, Embase, Web of Science, ClinicalTrials.gov, and Cochrane Library from their inception to 16 August 2023. Randomized controlled trials (RCTs) comparing sotagliflozin with a placebo, dapagliflozin, and empagliflozin in adult T2DM patients with HF or CV risks for at least 12 weeks were included in the study. Data analysis was conducted using R 4.2.3 and Stata 17.0. Cardiovascular efficacy outcomes included HF events (hospitalization or urgent visits for HF), MACE (deaths from CV causes, hospitalizations for HF, nonfatal myocardial infarctions, and strokes), cardiovascular death, the decrease in SBP, and weight loss. Safety outcomes are urinary tract infection, diarrhea, and diabetic ketoacidosis. Results: Eleven studies with 30,952 patients were included. Compared to dapagliflozin and empagliflozin, 200 mg of sotagliflozin showed the best effect in reducing HF events [OR (95% CI), 0.79 (0.66, 0.94) and 0.90 (0.63, 1.27)]. Compared to dapagliflozin, 200 mg of sotagliflozin [OR (95% CI), 0.76 (0.66, 0.87)] was superior in preventing MACE. Compared to empagliflozin, 200 mg of sotagliflozin [OR (95% CI), 1.46 (1.04, 2.05)] was inferior in preventing CV death. Sotagliflozin showed a poorer SBP decreasing effect than empagliflozin and dapagliflozin [MD (95% CI), 1.30 (0.03, 2.56) and 2.25 (0.35, 4.14), respectively]. There was no significant difference between sotagliflozin and other interventions in weight loss. Sotagliflozin exhibited no increased risk for diabetic ketoacidosis or urinary tract infection among all interventions, however, it showed a mild risk for diarrhea than placebo [OR (95% CI), 1.47 (1.28, 1.69)]. Conclusion: Sotagliflozin displayed moderate CV benefits and acceptable safety. Sotagliflozin can be one of the recommended options for T2DM patients with HF or CV risk factors, which will be important for evidence-based use of sotagliflozin as well as decision-making of T2DM medication.

Exploring the Cardiovascular Benefits of Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors: Expanding Horizons Beyond Diabetes Management.

Globally, cardiovascular disease (CVD) continues to be the primary cause of morbidity and mortality. The risk of cardiovascular disease is markedly increased in individuals with type 2 diabetes mellitus (T2DM), making managing cardiovascular health a top priority. Initially developed for their glucose-lowering properties, sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as a transformative class of pharmaceuticals with profound cardiovascular benefits that extend far beyond glycemic control. One of the most striking findings is the substantial reduction in major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and cardiovascular mortality, observed in clinical trials evaluating SGLT2 inhibitors. These extraordinary cardioprotective effects are demonstrated by landmark trials such as EMPA-REG OUTCOME, CANVAS, and DECLARE-TIMI 58, which are discussed in detail. In addition, SGLT2 inhibitors have demonstrated positive outcomes in heart failure (HF) with reduced ejection fraction, which has led to their incorporation into HF treatment guidelines. SGLT2 inhibitors offer renoprotection by delaying the progression of diabetic kidney disease, reducing albuminuria, preserving glomerular filtration rates, and their immediate cardiovascular benefits. We investigate the potential mechanisms underlying these renal benefits, focusing on the role of hemodynamic alterations and intraglomerular pressure reduction. In addition, SGLT2 inhibitors have a distinct diuretic effect that can contribute to volume reduction and symptom alleviation in patients with heart failure (HF). This diuretic action, distinct from conventional diuretics, warrants additional research to optimize their use in T2DM and HF patients. The risk of euglycemic diabetic ketoacidosis, genital mycobacterial infections, and bone fractures are also discussed. Understanding these issues is essential for making educated clinical decisions. In conclusion, SGLT2 inhibitors have transcended their initial function as anti-diabetic agents to become essential components of cardiovascular and renal protection strategies in T2DM patients. Their diverse benefits, which include cardioprotection, renoprotection, and the potential for HF management, highlight their potential to transform cardiovascular medicine. Optimizing the use of SGLT2 inhibitors in clinical practice bears the promise of improved cardiovascular outcomes for patients with T2DM and beyond as we navigate this changing landscape.

Reducing the 10-year risk of ischemic cardiovascular disease to receive early cardiovascular benefits from bariatric surgery for obesity in China.

Background: Cardiovascular risk due to obesity can be improved greatly by bariatric surgery. However, there is no research involving appropriate model for evaluating cardiovascular disease risk reduction in bariatric surgery for obesity in China. We selected the ischemic cardiovascular disease (ICVD) risk score that accurately predict cardiovascular risk in Chinese adults to evaluate the 10-year risk of ICVD and estimated early cardiovascular benefits of bariatric surgery in obese Chinese patients through its reduction. Methods: From 2017 to 2019 we followed up 107 patients 6 months after surgery and measured the ICVD 10-year risk and other cardiovascular factors before and after surgery. Results: There were significant reductions in the ICVD total score (p < 0.001) and ICVD 10-year risk (%) (p < 0.001) 6 months post-operation compared with baseline. Furthermore, we found significant reductions in body mass index (BMI), body adiposity index (BAI), low-density lipoprotein (LDL), small dense-low-density lipoprotein (sd-LDL) and triglycerides (TG) 6 months after surgery compared with pre-operation (all p < 0.05). The decrease in ICVD total score was correlated with excess BMI loss (%EBMIL), reduced BAI, reduced LDL, reduced sd-LDL and reduced TG respectively (all p < 0.05) at 6 months post-operation. Moreover, there were significant reductions in the ICVD total score in the male subgroup [3 (3, 5) vs. 2.5 (2, 4), p < 0.001] and female subgroup [3 (2, 4) vs. 2 (1, 3), p < 0.001] 6 months post-operation compared with baseline. At last there were also significant reductions in the ICVD total score in the diabetic subgroup [5 (4, 6) vs. 4 (3, 5), p < 0.001] and non-diabetic subgroup [2 (2,3) vs. 2 (1, 2), p < 0.001] 6 months post-operation compared with baseline. Conclusions: Bariatric surgery could provide early cardiovascular benefits for patients with obesity in China by reducing the 10-year risk of ICVD. Both men and women with obesity achieved cardiovascular benefits according to bariatric surgery, so did diabetic and non-diabetic patients.

The Cardiovascular Benefits and Infections Risk of SGLT2i versus Metformin in Type 2 Diabetes: A Systemic Review and Meta-Analysis.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and metformin are both widely accepted anti-hyperglycemic agents. However, there is still no systematic review evaluating the cardiovascular benefits and risk of infections of SGLT2i versus metformin. To make that clear, we designed this study. Public databases, including the Cochrane library database, PubMed, and Embase were searched for randomized clinical trials (RCTs) fitting the inclusion criteria. Two reviewers extracted the data and appraised the study quality independently. Thirteen RCTs enrolling 4189 patients were eligible for this analysis. Our results showed that compared with metformin, SGLT2i increased the risk of genitourinary tract infections (p < 0.00001). Further subgroup analysis suggested that the occurrence of urinary tract infections (UTI) was not statistically significant (p = 0.18), but the incidence of reproductive tract infections (RTI) was significantly increased in patients in the SGLT2i group compared with that in the metformin group (p < 0.00001). In addition, SGLT2i markedly decreased the levels of cardiovascular risk factor, including body weight, blood pressure, and triglyceride level, and significantly increased the HDL-cholesterol level (p < 0.00001) in patients versus that of metformin. For type 2 diabetes patients with obesity, SGLT2i was associated with more significant reductions in weight and blood pressure compared to metformin without an increased risk of genitourinary infections, and the reduction in fasting plasma glucose was superior in the SGLT2i group; the decrease in HbA1c was similar in both groups. Additionally, no significant publication bias was seen. Based on these findings, SGLT2i provided the similar antihyperglycemic effects, additional cardiovascular benefits, and a potential RTI risk compared with that of metformin. Our results indicate that SGLT2i is a good choice for those patients with metformin intolerance or resistance.

Evolving channeling in prescribing SGLT-2 inhibitors as first-line treatment for type 2 diabetes.

PURPOSE: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are increasingly being considered as first-line treatment for type 2 diabetes (T2D). The benefits of SGLT-2i from cardiovascular outcome trials may lead to preferential prescribing of SGLT-2i to patients at high cardiovascular risk, possibly causing confounding in non-randomized studies of SGLT-2i as first-line treatment. We assessed evolving imbalances in characteristics of patients starting SGLT-2i versus metformin as first-line monotherapy. METHODS: Using claims data from two US commercial health insurance and Medicare, we identified patients with T2D aged ≥18 years (>65 years in Medicare) initiating first-line SGLT-2i or metformin from 2013 through 2019. Standardized differences (SDs) for patient characteristics were assessed during four consecutive calendar time blocks (T1:4/2013-12/2014; T2:1/2015-6/2016; T3:7/2016-12/2017; and T4:1/2018-12/2019). We also estimated the propensity score of receiving SGLT-2i versus metformin within each time block and evaluated time trends in model discrimination with c-statistics. RESULTS: We identified 9113 initiators of first-line SGLT-2i and 810 348 initiators of first-line metformin. During T1, SGLT-2i initiators were younger (SD = -0.24) and less likely to have seen cardiologists (-0.07) with a similar prevalence of CVD (0.04) compared with metformin. During T4, patients were more balanced for age (-0.01). Cardiologist visits (0.08) and CVD (0.25) became more prevalent among SGLT-2i initiators. CONCLUSIONS: When comparing initiators of first-line SGLT-2i versus metformin, imbalances in patient characteristics evolved from 2013 through 2019, particularly channeling SGLT-2i to individuals at high cardiovascular risk. Evolving channeling in prescribing first-line SGLT-2i should be expected and accounted for in non-randomized comparative effectiveness research.

Prevalence of cardiovascular events among patients with type 2 diabetes in the west region of Saudi Arabia.

Background: Diabetes mellitus (DM) remains a concern globally and particularly in Saudi Arabia, where its prevalence is continuously increasing among the Saudi population. DM is known to increase the risk of cardiovascular disease (CVD), which can progress significantly if DM is poorly controlled. Aim: Determine the prevalence of cardiovascular events among patients with type 2 diabetes (T2DM) in the west region of Saudi Arabia, and additionally the use of antidiabetic agents with cardiovascular benefits (ADc) in T2DM patients with cardiovascular events (CVEs). Method: A retrospective cohort study was conducted among all patients with T2DM who presented to the diabetic center of Prince Mansour Military Hospital (PMMH), Taif city, between the 1st of January and 30th of June 2021. Data extracted from patient medical records included demographics, home medications, medications used to treat T2DM, lab results, and ECG data. Descriptive statistics were used to analyze and compare the results. The study was approved by the Research and Ethics Committee of Medical Services General Directorate, Armed Forces Hospitals, Taif region. Result: A total of 349 patients with T2DM were recruited and included in the final analysis. Of this study population, 132 patients had experienced at least one cardiovascular event while 54 were considered to be at risk of future cardiovascular events due to having risk factors for cardiovascular diseases above and beyond the presence of diabetes. A subgroup analysis was conducted to examine HbA1c% among all groups; interestingly, all were similar, with p > 0.05. Of all diabetic patients with CVEs, only 34.8 % were on at least one anti-diabetic agent known to have cardiovascular benefits; the remainder were on other anti-diabetic agents. A similar analysis was conducted on diabetic patients with risk of CVEs, of which only 13 % were on at least one anti-diabetic agent having known cardiovascular benefits; the remainder were on other anti-diabetic agents. Conclusion: The prevalence of CVEs among T2DM patients in Saudi Arabia is very close to the global prevalence, but ADcs are underutilized in this population. Tighter glycemic control is warranted to help rein in and reduce the CVE incidence among patients with T2DM.

Cardiovascular Effects of Chocolate and Wine-Narrative Review.

The consumption of food for pleasure is mainly associated with adverse health effects. This review was carried out to verify recent reports on the impact of chocolate and wine consumption on cardiovascular health, with a particular focus on atherosclerosis. On one side, these products have proven adverse effects on the cardiovascular system, but on the other hand, if consumed in optimal amounts, they have cardiovascular benefits. The submitted data suggest that the beneficial doses are 30-50 g and 130/250 mL for chocolate and wine, respectively, for women and men. The accumulated evidence indicates that the active ingredients in the products under consideration in this review are phenolic compounds, characterized by anti-inflammatory, antioxidant, and antiplatelet properties. However, there are also some reports of cardioprotective properties of other compounds such as esters, amines, biogenic amines, amino acids, fatty acids, mineral ingredients, and vitamins. Our narrative review has shown that in meta-analyses of intervention studies, consumption of chocolate and wine was positively associated with the beneficial outcomes associated with the cardiovascular system. In contrast, the assessment with the GRADE (Grading of Recommendations Assessment, Development and Evaluation) scale did not confirm this phenomenon. In addition, mechanisms of action of bioactive compounds present in chocolate and wine depend on some factors, such as age, sex, body weight, and the presence of additional medical conditions. Patients using cardiovascular drugs simultaneously with both products should be alert to the risk of pharmacologically relevant interactions during their use. Our narrative review leads to the conclusion that there is abundant evidence to prove the beneficial impact of consuming both products on cardiovascular health, however some evidence still remains controversial. Many authors of studies included in this review postulated that well-designed, longitudinal studies should be performed to determine the effects of these products and their components on atherosclerosis and other CVD (Cardiovascular Disease) disease.

Cardiovascular benefits of sodium-glucose cotransporter 2 inhibitors in diabetic and nondiabetic patients.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were developed as antidiabetic agents, but accumulating evidence has shown their beneficial effects on the cardiovascular system. Analyses of the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) suggested that these benefits are independent of glycemic control. Several large-scale outcome trials of SGLT2i also showed cardiovascular benefits in nondiabetic patients, strengthening this perspective. Extensive animal and clinical studies have likewise shown that mechanisms other than the antihyperglycemic effect underlie the cardiovascular benefits. Recent clinical guidelines recommend the use of SGLT2i in patients with type 2 diabetes mellitus and cardiovascular diseases because of the proven cardiovascular protective effects. Since the cardiovascular benefits are independent of glycemic control, the therapeutic spectrum of SGLT2i will likely be extended to nondiabetic patients.

Efficacy and Cardiovascular Safety of SGLT2 Inhibitors.

Patients with diabetes continued to exhibit a high risk for cardiovascular and renal events despite achieving satisfactory glycemic, blood pressure and lipid targets. Studies evaluating new diabetes medications focused on cardiovascular events, largely overlooking heart failure (HF). The latter has recently been recognised as a major cause of morbidity and mortality in patients with diabetes mellitus. There had been an unmet need for drugs with cardiovascular (including HF) and renal protection, with an expectation that an ideal diabetic drug should improve these endpoints. Moreover, an ideal drug should have weight reducing benefits. Recently published outcome trials have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1RAs) can reduce cardiovascular and renal events, together with statistically significant weight reduction. As a result, many recently published international guidelines have recommended SGLT2 inhibitors and GLP-1RAs in patients with diabetes and pre-existing cardiovascular disease (CVD). In this review, we will critically analyse the efficacy and cardiovascular (CV) safety of SGLT2 inhibitors, based on the available literature to help position them in the clinical decision process.

Cardiovascular effects and mechanisms of sodium-glucose cotransporter-2 inhibitors.

Sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) are a new type of drug for the treatment of diabetes, and they have been proven to have a good hypoglycemic effect. Several lines of clinical evidence have shown that SGLT2 inhibitors can significantly reduce the risks of atherosclerosis, hospitalization for heart failure, cardiovascular death, and all-cause mortality and delay the progression of chronic kidney disease. Because of the protective effects of SGLT2 inhibitors on the heart and kidney, they are being studied for the treatment of heart failure and chronic kidney disease in patients without diabetes. Therefore, it is necessary for cardiologists, patients with diabetes, and nephrologists to fully understand this type of drug. In this review, we summarize the following three aspects of SGLT2 inhibitors: the recent clinical evidence of their cardiovascular benefits, their mechanisms of action, and their safety.

Cardiovascular Effects of Sodium Glucose Co-transporter-2 Inhibitors in Patients with Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM), the leading type of diabetes, has a typical association with coronary heart disease. In India, patients with diabetes are at an increased risk of developing coronary disease as compared to people without diabetes and this suggests the requirement of intensive treatment of cardiovascular (CV) risk factors. Consequently, there is a need for an intervention that could target CV risk factors in multiple paths beyond hyperglycemic control alone. Although metformin is the mainstay of treatment in most of the patients with T2DM, a second line of treatment with anti-hyperglycemic agent is warranted in patients with T2DM in the management of CV risk factors beyond glycemic control. Sodium glucose co-transporter-2 (SGLT-2) inhibitors, the oral hypoglycemic drug, that act independent of insulin secretion are associated with a reduced risk of hypoglycemia which is associated with the increased risk of CV events. Moreover, it has been observed that the use of SGLT-2 inhibitors in patients with T2DM is associated with reductions in blood pressure and body weight beyond improved glycemic control. In this article, the clinical efficacy, safety, and tolerability of SGLT-2 inhibitors on glycemic, nonglycemic parameters, and CV outcome including data from the EMPA-REG OUTCOME study are discussed. The EMPA-REG OUTCOME study is the first CV outcome study that demonstrated the association of a glucose lowering agent with the reduced CV mortality and all-cause mortality, and reduced hospitalization for heart failure in patients with T2DM at high risk of CV events. Although the mode of action associated with the CV benefits remains unknown, data from ongoing trials including DECLARE-TIMI (Dapagliflozin Effect on CV Events) and CANVAS (Canagliflozin CV Assessment Study) trials potentially can validate the class-effect for SGLT-2 inhibitors regarding the CV outcomes.

Further insights into cardiovascular outcomes in diabetic and non-diabetic states: inhibition of sodium-glucose co-transports.

Cardiovascular diseases are the leading cause of morbidity and mortality in the world. Diabetes increase heart disease related to death by two- to four-fold. SGLT2 inhibitors are new antidiabetic agents. The growing evidence of cardiovascular benefit of SGLT2 inhibitors independent of their effects on glycemic control is especially intriguing. Several clinical trials have shown that sotagliflozin (SGLT1-1/2 inhibitor) decreases body weight and reduces blood pressure in adults with T2D. A phase 3 study designed to evaluate cardiovascular outcomes of sotagliflozin is currently ongoing. Many pre-clinical studies were conducted to investigate the potential mechanisms involved in cardiovascular benefits of SGLT1 or SGLT2 inhibition with or without diabetes. Although multiple mechanisms have been proposed, there are still not enough data to fully support the mechanisms of actions. This review aims to discuss the potential mechanisms involved in cardiovascular benefits of SGLT1 and SGLT2 inhibition in both diabetic and non-diabetic states.