Bioengineered Human Arteries for the Repair of Vascular Injuries.

Importance: Vascular injuries require urgent repair to minimize loss of limb and life. Standard revascularization relies on autologous vein or synthetic grafts, but alternative options are needed when adequate vein is not feasible and when clinical conditions preclude safe use of synthetic materials.

Objective: To evaluate the performance of the acellular tissue engineered vessel (ATEV) in the repair of arterial injuries.

Case of ST-Elevation Myocardial Infarction in a 32-Year-Old Male Receiving Bleomycin, Etoposide, and Cisplatin Chemotherapy for Embryonal Carcinoma.

Myocardial infarction in young individuals has unique risk factors compared to the older population. Along with usual risk factors, one should explore causes such as recreational drug use, medication-induced myocardial infarction, and spontaneous coronary artery dissection. Here, we present the case of a 32-year-old male who presented with chest pain and was found to have complete thrombotic occlusion of the right coronary artery.

Pancreatitis, panniculitis and polyarthralgia syndrome: A rare complication of pancreatic pathology.

Pancreatitis, panniculitis, and polyarthralgia (PPP) syndrome is a rare complication of chronic pancreatitis and occurs due to leakage of pancreatic enzymes in the systemic vasculature. This enzyme leakage leads to multiple manifestations such as polyarthralgia, panniculitis, and bone necrosis due to tissue autodigestion.The inciting pancreatic pathology may be masked, and the presentation may be due to one of the systemic consequences of enzyme leakage, which can present as a diagnostic challenge for clinicians.

Long-Term Safety of Dapagliflozin in Older Patients with Type 2 Diabetes Mellitus: A Pooled Analysis of Phase IIb/III Studies.

Objective: To evaluate the 104-week safety of dapagliflozin in older patients with type 2 diabetes mellitus.

Methods: Pooled analysis assessing general safety (nine phase III studies ≤104 weeks) and cardiovascular safety (21 phase IIb/III studies ≤208 weeks) by age (<65; ≥65; ≥75 years). Patients with type 2 diabetes mellitus (±background glucose-lowering therapy) received: dapagliflozin 10 mg (n = 2026) vs.

Bioequivalence of fixed-dose combinations of dapagliflozin and metformin with single-component tablets in healthy subjects and the effect of food on bioavailability.

The pharmacokinetics (PK) of dapagliflozin and metformin administered as fixed-dose combination (FDC) tablets (2.5 mg dapagliflozin/850 mg metformin or 5 mg dapagliflozin/1000 mg metformin) or as separate tablets in healthy subjects were evaluated in 2 separate studies. Study 1 evaluated PK by measuring mean ratios of area under the plasma concentration-time curve (time zero to infinity [AUCinf ]), AUC from zero to time of last measurable concentration (AUC0-t ), and maximum observed plasma concentration (Cmax ) for single-component or FDC tablets following a non-high-fat meal.

The effect of dapagliflozin on renal function in patients with type 2 diabetes.

Background: Dapagliflozin's antihyperglycemic effects are mediated by inhibition of renal sodium-glucose cotransporter-2; therefore, renal safety of dapagliflozin was assessed.

Methods: Twelve double-blind, placebo-controlled, randomized clinical trials were analyzed up to 24 weeks (N = 4545). Six of the 12 studies included long-term data for up to 102 weeks (N = 3036).

Osmotic diuresis with SGLT2 inhibition: analysis of events related to volume reduction in dapagliflozin clinical trials.

Objective: Dapagliflozin reduces hyperglycemia in type 2 diabetes mellitus (T2DM) and lowers blood pressure, at least in part, secondary to mild diuresis consequent to dapagliflozin-induced glucosuria. While blood-pressure lowering may contribute to cardiovascular risk reduction, dapagliflozin-induced diuresis may potentially contribute to adverse events (AEs) of volume reduction. The present analysis compared the frequency of AEs of volume reduction between dapagliflozin and placebo.

Effect of the SGLT2 Inhibitor Dapagliflozin on Potassium Levels in Patients with Type 2 Diabetes Mellitus: A Pooled Analysis.

Introduction: Hyperkalemia risk is increased in diabetes, particularly in patients with renal impairment or those receiving angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) or potassium-sparing diuretics. Conversely, other diuretics can increase hypokalemia risk. We assessed the effects of the sodium glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin on serum potassium levels in a pooled analysis of clinical trials in patients with type 2 diabetes mellitus (T2DM).

Effects of dapagliflozin on blood pressure in hypertensive diabetic patients on renin-angiotensin system blockade.

Hypertension and type 2 diabetes mellitus (T2DM) are risk factors for cardiovascular disease. Dapagliflozin improves glycemic control and systolic blood pressure (SBP) in T2DM patients. This double-blind phase III study evaluated the effects of dapagliflozin on glycemic control and blood pressure in patients with inadequately controlled T2DM and hypertension, despite ongoing therapy with a renin-angiotensin system blocker.

Blood pressure and glycaemic effects of dapagliflozin versus placebo in patients with type 2 diabetes on combination antihypertensive therapy: a randomised, double-blind, placebo-controlled, phase 3 study.

Background: Hypertension is a common comorbidity in patients with type 2 diabetes mellitus and a major risk factor for microvascular and macrovascular disease. Although the blood pressure-lowering effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors are already established, guidance is needed on how to use these drugs in patients already receiving antihypertensive therapy. We aimed to compare blood pressure and glycaemic effects of the SGLT2 inhibitor dapagliflozin with placebo in patients with inadequately controlled type 2 diabetes mellitus and hypertension.

Dapagliflozin's Effects on Glycemia and Cardiovascular Risk Factors in High-Risk Patients With Type 2 Diabetes: A 24-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study With a 28-Week Extension.

Objective: To assess the efficacy and safety of dapagliflozin, a selective sodium-glucose cotransporter 2 inhibitor, compared with placebo in patients with type 2 diabetes (T2D), documented pre-existing cardiovascular disease (CVD), and a history of hypertension.

Research Design And Methods: Patients (N = 922) were randomized to receive 10 mg dapagliflozin or placebo in a double-blind trial for 24 weeks, followed by a 28-week extension period. In patients receiving insulin, the insulin dose was reduced by 25% at randomization.

Dapagliflozin improves glycemic control and reduces body weight as add-on therapy to metformin plus sulfonylurea: a 24-week randomized, double-blind clinical trial.

Objective: To evaluate the efficacy and safety of dapagliflozin in patients with type 2 diabetes inadequately controlled with metformin and sulfonylurea.

Research Design And Methods: Patients with HbA1c of 7.0% (53 mmol/mol) to 10.

Safety profile of dapagliflozin for type 2 diabetes: pooled analysis of clinical studies for overall safety and rare events.

Background: Dapagliflozin reduces hyperglycaemia in patients with type 2 diabetes mellitus (T2DM) by increasing urinary glucose excretion.

Objectives: This study determined the overall safety profile of dapagliflozin in T2DM.

Methods: Safety of dapagliflozin in pooled analyses of phase IIb/III studies was evaluated.

Dapagliflozin added to glimepiride in patients with type 2 diabetes mellitus sustains glycemic control and weight loss over 48 weeks: a randomized, double-blind, parallel-group, placebo-controlled trial.

Introduction: Maintenance of drug efficacy and safety over the long term is important to investigate for progressive conditions like type 2 diabetes mellitus (T2DM). This study aimed to evaluate whether efficacy of dapagliflozin added to glimepiride observed at 24 weeks was maintained at 48 weeks, and to provide further safety and tolerability data in patients with T2DM.

Methods: This 24-week randomized, double-blind, parallel-group, placebo-controlled trial with a 24-week double-blind extension period enrolled adults whose T2DM was inadequately controlled [glycated hemoglobin (HbA1c) 7.

Dapagliflozin added to usual care in individuals with type 2 diabetes mellitus with preexisting cardiovascular disease: a 24-week, multicenter, randomized, double-blind, placebo-controlled study with a 28-week extension.

Objectives: To assess the efficacy of dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, for the treatment of individuals with type 2 diabetes mellitus (T2DM) and preexisting cardiovascular disease (CVD).

Design: Randomized, double-blind, age-stratified (<65 and ≥ 65), 24-week clinical trial with a 28-week extension.

Setting: One hundred seventy-three centers in 10 countries.

Genital and urinary tract infections in diabetes: impact of pharmacologically-induced glucosuria.

Predisposition to genital infections and urinary tract infections (UTIs) in type 2 diabetes mellitus (T2DM) results from several factors such as glucosuria, adherence of bacteria to the uroepithelium and immune dysfunction. The tendency to develop these infections could be even higher in patients with T2DM treated with the emerging class of sodium-glucose cotransporter-2 (SGLT2) inhibitors. Studies have shown that pharmacologically-induced glucosuria with SGLT2 inhibitors raises the risk of developing genital infections and, to a relatively lesser extent, UTIs.

Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebo-controlled study.

Objective: To assess the efficacy and safety of dapagliflozin as add-on therapy in patients with type 2 diabetes who were inadequately controlled with a dipeptidyl peptidase-4 inhibitor with or without metformin.

Research Design And Methods: In this 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 study with a 24-week blinded extension period, 432 patients were randomized to receive dapagliflozin 10 mg/day or placebo added to sitagliptin (100 mg/day) ± metformin (≥1,500 mg/day).

Results: Baseline HbA1c and FPG levels were 7.

Urinary tract infections in patients with diabetes treated with dapagliflozin.

Aims: Urinary tract infection is common in patients with type 2 diabetes. Possible causative factors include glucosuria, which is a result of treatment with sodium glucose cotransporter 2 (SGLT2) inhibitors. Dapagliflozin is an investigative SGLT2 inhibitor with demonstrated glycemic benefits in patients with diabetes.

Vulvovaginitis and balanitis in patients with diabetes treated with dapagliflozin.

Background: Vulvovaginitis, balanitis, and related genital infections are common in patients with type 2 diabetes. Glucosuria, which is an outcome of treatment with sodium glucose cotransporter 2 (SGLT2) inhibitors, is among the possible causes. Dapagliflozin, an SGLT2 inhibitor with demonstrated glycemic benefits in patients with diabetes, has been studied across a broad spectrum of patients.

Effects of dapagliflozin on cardiovascular risk factors.

People with diabetes are more likely to develop a cardiovascular (CV) disease compared with those without diabetes. Although effective glycemic control has been the focus of the management of type 2 diabetes mellitus (T2DM), it is also important to control other CV risk factors to improve outcomes in these patients. Dapagliflozin, a sodium-glucose co-transporter 2 inhibitor, lowers glucose levels in patients with T2DM by increasing urinary glucose excretion.

Targeting the kidney and glucose excretion with dapagliflozin: preclinical and clinical evidence for SGLT2 inhibition as a new option for treatment of type 2 diabetes mellitus.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a novel class of glucuretic, antihyperglycemic drugs that target the process of renal glucose reabsorption and induce glucuresis independently of insulin secretion or action. In patients with type 2 diabetes mellitus, SGLT2 inhibitors have been found to consistently reduce measures of hyperglycemia, including hemoglobin A1c, fasting plasma glucose, and postprandial glucose, throughout the continuum of disease. By inducing the renal excretion of glucose and its associated calories, SGLT2 inhibitors reduce weight and have the potential to be disease modifying by addressing the caloric excess that is believed to be one of the root causes of type 2 diabetes mellitus.

Targeting renal glucose reabsorption for the treatment of type 2 diabetes mellitus using the SGLT2 inhibitor dapagliflozin.

Sodium-glucose co-transporter 2 (SGLT2) plays a key role in glucose homeostasis as the key transporter responsible for most renal glucose reabsorption in the proximal tubules of the kidney. Dapagliflozin is a potent, selective, and reversible inhibitor of SGLT2 that lowers blood glucose levels in an insulin-independent fashion. This novel agent has been studied extensively in patients with type 2 diabetes mellitus (T2DM).

Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses of insulin: a randomized trial.

Background: Dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2, may improve glycemic control with a lower dose of insulin and attenuate the associated weight gain in patients with inadequate control despite high doses of insulin.

Objective: To evaluate the efficacy and safety of adding dapagliflozin therapy in patients whose type 2 diabetes mellitus is inadequately controlled with insulin with or without oral antidiabetic drugs.

Design: A 24-week, randomized, placebo-controlled, multicenter trial followed by a 24-week extension period.

Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.

Context: Dapagliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, reduces hyperglycemia in patients with type 2 diabetes mellitus (T2DM) by increasing urinary glucose excretion, and weight loss is a consistent associated finding.

Objectives: Our objectives were to confirm weight loss with dapagliflozin and establish through body composition measurements whether weight loss is accounted for by changes in fat or fluid components.

Design And Setting: This was a 24-wk, international, multicenter, randomized, parallel-group, double-blind, placebo-controlled study with ongoing 78-wk site- and patient-blinded extension period at 40 sites in five countries.

Evaluation of the effect of dapagliflozin on cardiac repolarization: a thorough QT/QTc study.

Introduction: Dapagliflozin is a first-in-class sodium-glucose transporter 2 (SGLT2) inhibitor under investigation for the treatment of type 2 diabetes mellitus. A thorough QTc study was conducted, according to International Conference on Harmonization E14 guidelines, to characterize the effect of dapagliflozin on cardiac repolarization.

Methods: The present study was a double-blind, four-period, placebo-controlled crossover study at a single-center inpatient clinical pharmacology unit.