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The effect of dapagliflozin on blood pressure was evaluated in non-hypertensive (<140 mm Hg) and hypertensive (⩾140 mm Hg) patients with type 2 diabetes mellitus. Data were pooled from 13 placebo-controlled studies. Patients received dapagliflozin 10 mg/day (n = 2360) or placebo (n = 2295) for up to 24 weeks. Dapagliflozin was associated with place...
Fragestellung: Es sollte die zeitabhangige Veranderung der Nuchternplasmaglukose (NPG), des HbA1c sowie des Korpergewichtes (KG) unter Dapagliflozin (DAPA) als Add-on zu Metformin (MET) bzw. unter der initialen DAPA/MET-Kombination untersucht werden. Methodik: Zwei randomisierte Studien wurden durchgefuhrt: 1) DAPA 10 mg/Tag vs. Placebo als Add-on...
Fragestellung: Dapagliflozin (DAPA) verringert die Blutglukose bei T2DM-Patienten, indem es die renale Glukoseausscheidung erhoht, was mit einer milden osmotischen Diurese einhergeht. Daher wurden Sicherheit und Vertraglichkeit von DAPA hinsichtlich Diurese untersucht. Methodik: Gepoolte Daten aus 13 placebokontrollierten, doppelblinden, bis zu 24-...
Fragestellung: Dapagliflozin (DAPA) verbessert die glykamische Kontrolle, indem es die renale Glukoseausscheidung erhoht. Die Vertraglichkeit von DAPA bei alteren Patienten mit T2DM wurde in neun placebokontrollierten, doppelblinden Phase-2b/3-Langzeitstudien uber 104 Wochen untersucht. Methodik: Die Studienteilnehmer erhielten 10 mg DAPA (n = 2026...
Fragestellung: Hohe HbA1c-Werte gehen mit erhohter Morbiditat und Mortalitat einher. Aktuelle Leitlinien empfehlen eine duale Therapie als eine Option bei Patienten mit einem HbA1c-Wert ≥9,0%. Dapagliflozin (DAPA), ein selektiver SGLT-2 Inhibitor, reduziert die Plasmaglukose unabhangig von der Insulinsekretion und -aktivitat, indem es die renale Gl...
Fragestellung: Es wurde uber ein vermehrtes Auftreten von Hyperkaliamien bei Anwendung des SGLT-2 Inhibitors Canagliflozin berichtet. Daher beschreiben wir hier die Auswirkungen des hochselektiven SGLT-2 Inhibitors Dapagliflozin (DAPA) auf den Serumkaliumspiegel bei T2DM-Patienten. Methodik: Ausgewertet wurden gepoolte Daten aus 13 placebokontrolli...
Fragestellung: In Ubereinstimmung mit einer milden Diurese und einer Gewichtsverringerung reduziert der hochselektive SGLT-2 Inhibitor Dapagliflozin (DAPA) den Blutdruck bei T2DM-Patienten. Das kardiovaskulare Risiko kann durch Blutdrucksenkung – unabhangig vom Ausgangswert – verringert werden. Daher wurde die Wirksamkeit von DAPA auf den Blutdruck...
Background: Hypertension is a common comorbidity in patients with type 2 diabetes mellitus (T2DM). Initial treatment is usually with an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB), with other antihypertensive therapies (AHTs) added if needed. Dapagliflozin (DAPA) increases urinary glucose excretion accomp...
Dapagliflozin (DAPA), a sodium-glucose cotransporter 2 inhibitor, reduces plasma glucose in patients (pts) with type 2 diabetes by inhibiting renal glucose reuptake leading to glucosuria. DAPA has diuretic and longterm weight loss effects, and is associated with blood pressure (BP) reduction. Diuresis and BP reduction are evident soon after commenc...
Methods are provided for treating obesity or causing weight loss in a mammalian subject or patient, wherein a therapeutically effective amount of an SGLT2 inhibitor alone or optionally in combination with another anti-obesity agent, is administered to a mammalian subject or patient. In addition, a pharmaceutical composition is provided which compri...
AimsTo assess initial pharmacotherapy of Type 2 diabetes with the sodium-glucose cotransporter-2 inhibitor dapagliflozin.Methods
This double-blind, placebo-controlled trial, randomly allocated people with Type 2 diabetes aged 18–77 years and inadequate glycaemic control on diet and exercise [HbA1c 53–86 mmol/mol (7.0–10.0%)] to receive placebo (n=7...
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. Patients received comparato...
The invention provides methods for treating a patient having type 2 diabetes who has failed on previous regimens of one or more oral and/or injectable anti-diabetic agents, which include the step of administering a therapeutically effective amount of an SGLT2 inhibitor alone or in combination with another anti-diabetic agent and/or other therapeuti...
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-...
Dapagliflozin is a highly selective, orally active inhibitor of renal sodium-glucose cotransporter 2 that reduces hyperglycemia by increasing urinary glucose excretion. The goal of this study was to evaluate dapagliflozin as monotherapy in drug-naive Asian patients with type 2 diabetes whose disease was inadequately controlled with diet and exercis...
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. Data from dapagliflozin multi-trial...
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 ac...
Aims Sodium–glucose co-transporter 2 (SGLT2) reabsorbs glucose and sodium in the renal proximal tubule. Dapagliflozin, an SGLT2 inhibitor, targets hyperglycaemia in type 2 diabetes by increasing renal glucose excretion. To investigate whether the parallel occurring sodium loss would have diuretic-like physiologic effects, we compared dapagliflozin...
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...
Introduction
Dapagliflozine (DAPA), inhibiteur du SGLT2, réduit la glycémie en inhibant la réabsorption rénale du glucose et est en cours de développement chez des patients DT2
Matériels et méthodes
En raison du site d’action rénal de la DAPA, son effet sur la fonction rénale a été soigneusement évalué. Les données ont été recueillies à partir de...
Management of type 2 diabetes with metformin often does not provide adequate glycemic control, thereby necessitating add-on treatment. In a 24-week clinical trial, dapagliflozin, an investigational sodium glucose cotransporter 2 inhibitor, improved glycemic control in patients inadequately controlled with metformin. The present study is an extensio...
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 hyperglyce...
Many patients with type 2 diabetes are suboptimally managed with currently available therapies. Dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, has shown efficacy in reducing diabetic hyperglycaemia. This study assessed efficacy of three lower doses in recently diagnosed patients.
This phase 3, randomized, double-blind, placebo-controll...
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...
To examine the safety and efficacy of dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, added on to pioglitazone in type 2 diabetes inadequately controlled on pioglitazone.
Treatment-naive patients or those receiving metformin, sulfonylurea, or thiazolidinedione entered a 10-week pioglitazone dose-optimization period with only pioglitazone...
Combining metformin (XR) with dapagliflozin to initiate pharmacotherapy in patients with type 2 diabetes (T2D) and high baseline HbA1c may be advantageous. We conducted two randomised, double-blind, three-arm 24-week trials in treatment-naïve patients to compare dapagliflozin plus metformin, dapagliflozin alone and metformin alone.
Eligible patient...
Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular (CV) disease. Dapagliflozin (DAPA), a selective SGLT2 inhibitor, is currently under evaluation for the treatment of T2DM. DAPA reduces hyperglycemia by promoting renal glucose excretion, independent of insulin secretion or action, also reducing weight and blood p...
To study the effect of dipeptidyl peptidase-4 (DPP-4) inhibition with saxagliptin on β-cell function as reflected by the stimulated insulin secretion rate after an enteral glucose load in patients with type 2 diabetes.
Patients in this randomized, parallel-group, double-blind, placebo-controlled study were drug-naïve, aged 43-69 years, with baselin...
To assess the long-term efficacy and safety of saxagliptin in patients with type 2 diabetes mellitus inadequately controlled on sulphonylurea monotherapy, 768 patients were randomised to saxagliptin 2.5 or 5 mg in combination with glyburide 7.5 mg versus placebo added to up-titrated glyburide over 76 weeks (24 weeks plus 52-week extension) in this...
Glucose is freely filtered in the glomeruli before being almost entirely reabsorbed into circulation from the proximal renal tubules. The sodium-glucose cotransporter 2 (SGLT2), present in the S1 segment of the proximal tubule, is responsible for the majority of glucose reabsorption. SGLT2 inhibitors reduce glucose reabsorption and increase urinary...
The selective inhibition of sodium-glucose cotransporter 2 (SGLT2) has recently become a focus of potential type 2 diabetes mellitus (T2DM) therapeutics. This review describes the mechanism of SGLT2-induced urinary glucose excretion (UGE) and its effects on parameters of glycemic control in animal models, healthy humans, and patients with T2DM. Key...
Dapagliflozin, a highly selective inhibitor of the renal sodium-glucose cotransporter-2, increases urinary excretion of glucose and lowers plasma glucose levels in an insulin-independent manner. We evaluated the efficacy and safety of dapagliflozin in treatment-naive patients with type 2 diabetes.
This was a 24-week parallel-group, double-blind, pl...
Advances in experimental medicine and technological innovation during the past century have brought tremendous progress in modern medicine and generated an ever-increasing amount of data from bench and bedside. The desire to extend scientific knowledge motivates effective data integration. Technological innovation makes this possible, which in turn...
Correction of hyperglycaemia and prevention of glucotoxicity are important objectives in the management of type 2 diabetes. Dapagliflozin, a selective sodium-glucose cotransporter-2 inhibitor, reduces renal glucose reabsorption in an insulin-independent manner. We assessed the efficacy and safety of dapagliflozin in patients who have inadequate gly...
Dapagliflozin is a stable, competitive, reversible, and highly selective inhibitor of sodium-glucose co-transporter 2, the major transporter responsible for renal glucose reabsorption. With an insulin-independent mechanism of action, dapagliflozin is currently being developed for the treatment of type 2 diabetes mellitus (T2DM). This work aims to c...
To evaluate the efficacy and safety of once-daily saxagliptin monotherapy in treatment-naïve patients with type 2 diabetes (T2D) and inadequate glycemic control.
This study included a main treatment cohort (MTC) with 401 patients (HbA(1c) > or = 7% and < or =10%) randomized and treated with oral saxagliptin 2.5, 5, or 10 mg once daily or placebo fo...
To determine whether dapagliflozin, which selectively inhibits renal glucose reabsorption, lowers hyperglycemia in patients with type 2 diabetes that is poorly controlled with high insulin doses plus oral antidiabetic agents (OADs).
This was a randomized, double-blind, three-arm parallel-group, placebo-controlled, 26-center trial (U.S. and Canada)....
Assess the efficacy and safety of saxagliptin added to a submaximal sulphonylurea dose vs. uptitration of sulphonylurea monotherapy in patients with type 2 diabetes and inadequate glycaemic control with sulphonylurea monotherapy.
A total of 768 patients (18-77 years; HbA(1c) screening >or= 7.5 to <or= 10.0%) were randomised and treated with saxagli...
Dapagliflozin, a novel inhibitor of renal sodium-glucose cotransporter 2, allows an insulin-independent approach to improve type 2 diabetes hyperglycemia. In this multiple-dose study we evaluated the safety and efficacy of dapagliflozin in type 2 diabetic patients.
Type 2 diabetic patients were randomly assigned to one of five dapagliflozin doses,...
Enhancing the physiologic actions of the endogenous incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, by inhibiting dipeptidyl peptidase-4 (DPP-4), the enzyme responsible for their degradation, is an emerging treatment for type 2 diabetes mellitus (T2DM). The aim of this study was to evaluate the safety an...
Glucagon-like peptide-1 (GLP-1) is an insulinotropic hormone expressed by alternative post-translational processing of proglucagon in the intestines, endocrine pancreas, and brain. The multiple antidiabetogenic actions of GLP-1 include stimulation of the proliferation and differentiation of the insulin-producing beta cells in the pancreas. The GLP-...
Treatment of overtly diabetic NOD mice with anti-lymphocyte serum (ALS), a polyclonal anti-T-cell antibody, abrogates autoimmunity and achieves partial clinical remission. Here we investigated whether the addition of exendin-4, a hormone that stimulates insulin secretion and beta-cell replication and differentiation, improves induction of remission...
Glucagon-like peptide 1 (GLP-1) is an intestine-derived insulinotropic hormone that stimulates glucose-dependent insulin production and secretion from pancreatic beta-cells. Other recognized actions of GLP-1 are to suppress glucagon secretion and hepatic glucose output, delay gastric emptying, reduce food intake, and promote glucose disposal in per...
There has been a dramatic increase in the worldwide prevalence of obesity, a disorder with complex genetic traits that is influenced by environmental factors and that predisposes affected persons to diseases such as diabetes mellitus, hypertension, stroke, and heart attack. Since it has arisen with the increasing availability of easily obtainable c...
Proviral integration is thought to be an obligate step of the retroviral replication cycle but the lentivirus visna has been reported to replicate in sheep choroid plexus (SCP) cultures in the absence of proviral integration. Because of new evidence that visna virus has a functional integrase, we reexamined visna virus infection of SCP cultures and...
Hepatic fatty acid-binding protein (FABP) is one of several abundant proteins which may participate in fatty acid uptake and utilization. Using differential hybridization to screen for growth hormone-responsive gene products, a complementary deoxyribonucleic acid (cDNA) was isolated which proved to be a hepatic FABP cDNA fragment. Hypophysectomy ca...
Maedi and visna are, respectively, the pulmonary and neurological manifestations of slowly progressive infections of sheep caused by retroviruses of the lentivirus subfamily. Lentivirus infections are also persistent infections in which host defenses are generally not successful in eliminating the infectious agent because of restricted viral gene e...
Simian virus 40 (SV40) DNA replication was studied in monolayers of infected monkey CV-1 cells, permeabilized with lysolecithin, by incubation with [alpha-32P]dTTP, the other dNTPs and rNTPs and an ATP-regenerating system. Analysis of the labeled SV40 DNA by sedimentation in alkaline sucrose gradients showed that about 30% of the material synthesiz...
Simian virus 40 (SV40) DNA replication was studied in monolayers of infected monkey CV-1 cells, permeabilized with lysolecithin, by incubation with [α-32P]dTTP, the other dNTPs and rNTPs and an ATP-regenerating system. Analysis of the labeled SV40 DNA by sedimentation in alkaline sucrose gradients showed that about 30% of the material synthesized b...
