SGLT2i

PURPOSE OF REVIEW: In addition to their effects on glycemic control, two specific classes of relatively new anti-diabetic drugs, namely the sodium glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have demonstrated reduced rates of major adverse cardiovascular events (MACE) in subjects with type 2 diabetes (T2D) at high risk for cardiovascular disease (CVD). This review summarizes recent experimental results that inform putative molecular mechanisms underlying these benefits...

BACKGROUND: Cardiovascular (CV) safety of one anti-diabetic medication over another remains partially delineated. We sought to assess the comparative effect on CV outcomes among novel anti-diabetic agents. METHODS: This study was registered with the International Prospective Register of Systematic Reviews (CRD 42016042063). MEDLINE, EMBASE, and Cochrane Library Central Register of Controlled Trials were searched between Jan 1, 1980, and June 30, 2016. Randomized controlled trials comparing anti-diabetic drugs with other comparators in adults with type 2 diabetes were included...

BACKGROUND: The treatment of type 2 diabetes mellitus (T2DM) is complex; only few patients successfully attain glycemic targets with monotherapy, most requiring drug combination therapy. METHODS: The goal of this review was to identify in PubMed the complimentary ways of action leading to clinical benefit (in lowering HbA1c, body weight, renal, and cardiac risk factors and events) of the combination of sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA)...

AIMS: We examined dapagliflozin-induced changes in liver fat accumulation. METHODS: We prospectively recruited Japanese patients with inadequately controlled type 2 diabetes mellitus (T2DM) [hemoglobin A1c (HbA1c) <7.0%]. Dapagliflozin (5 mg/day) or non-sodium glucose cotransporter 2 inhibitors (SGLT2i) was added to the patients' treatment regimen for 6 months. Changes in liver fat accumulation were assessed by the liver-to-spleen (L/S) attenuation ratio using abdominal computed tomography (CT)...

Background: Therapy for Type 2 diabetes (T2D) has been transformed by the introduction of newer agents like Glucagon like Peptide Receptor Agonists (GLP-1RA) and Sodium-glucose linked transporter inhibitors (SGLT2i). However with co-initiation of SGLT2i and GLP-1RA in the DURATION 8 trial an improvement in HbA1c was noted but the beneficial effect was not equal to the sum of its parts. In view of this we proceeded to test the hypothesis that sequential addition of GLP-1RA therapy to metformin and SGLT-2i may be more beneficial...

BACKGROUND AND AIMS: Advanced hepatic fibrosis can occur in patients with various diseases, including diabetes mellitus and hypertension. We aimed to investigate the prevalence and risk factors of advanced hepatic fibrosis in patients with various internal diseases. PATIENTS AND METHODS: We performed a community-based survey in which 1,012 patients were enrolled (mean age, 63.1 ± 10.8 years; female/male, 505/507). Hepatic fibrosis was evaluated by Fib-4 index and patients were classified into high and low Fib-4 groups...

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are anti-diabetic drugs which improve blood glucose control by blocking reabsorption of glucose from the proximal tubule of kidney. Anti-atherosclerotic properties and cardiovascular protective effects of SGLT2i have been demonstrated by recent studies; however, the efficacy and safety of addition of SGLT2i to the intensive insulin therapy remain largely unknown. Methods: We retrospectively picked up patients hospitalized for treatment of type 2 diabetes, who had been treated by the intensive insulin therapy and whose treatment using by SGLT2i started during their hospitalization...

Background: We examined whether the sodium-glucose cotransporter-2 inhibitor (SGLT2i) dapagliflozin can improve urine albumin-to-creatinine ratio (UACR) associated with a reduction in body weight or body fat in patients with type 2 diabetes mellitus (T2DM). Methods: We prospectively recruited T2DM patients having inadequate glycemic control (hemoglobin A1c (HbA1c) > 7.0%) not on SGLT2i therapy. We treated the patients with add-on dapagliflozin treatment or intensification of non-SGLT2 inhibitor therapies for 6 months...

BACKGROUND: Type 2 diabetes (T2D) is associated with generalized vascular dysfunction characterized by increases in large artery stiffness, endothelial dysfunction, and vascular smooth muscle dysfunction. Sodium glucose cotransporter 2 inhibitors (SGLT2i) represent the most recently approved class of oral medications for the treatment of T2D, and have been shown to reduce cardiovascular and overall mortality. Although it is currently unclear how SGLT2i decrease cardiovascular risk, an improvement in vascular function is one potential mechanism...

The decrement in plasma glucose concentration with SGLT2 inhibitors (SGLT2i) is blunted by a rise in endogenous glucose production (EGP). We investigated the ability of incretin treatment to offset the EGP increase. Subjects with type 2 diabetes ( n = 36) were randomized to 1 ) canagliflozin (CANA), 2 ) liraglutide (LIRA), or 3 ) CANA plus LIRA (CANA/LIRA). EGP was measured with [3-3 H]glucose with or without drugs for 360 min. In the pretreatment studies, EGP was comparable and decreased (2.2 ± 0.1 to 1.7 ± 0...

We are now entering the very exciting era of treatment and management of diabetes mellitus (DM) with the emergence of new therapeutic agents, including sodium-glucose cotransporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitor (DPP-4i). From a cardiology and echocardiography perspective, the existence of diabetic cardiomyopathy has been proven through over four decades of discussion. DM is highly prevalent in patients with heart failure (HF). Independent associations are found after adjusting for hypertension (HTN) and coronary artery disease (CAD)...

Sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors have complementary mode of action. For the meta-analysis comparing the efficacy and safety between SGLT2 inhibitor plus DPP4 inhibitor (SGLT2i/DPP4i) and placebo plus DPP4 inhibitor (PCB/DPP4i) in patients with type 2 diabetes mellitus (T2DM), we selected randomized controlled trials from electronic databases by predefined criteria. The primary outcome of interest was the change in glycated hemoglobin A1c (HbA1c) from baseline...

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) exert their antidiabetic effects by promoting urinary glucose excretion. Nutrition therapy is obviously important, but little is known about the interactions between SGLT2i agents and carbohydrate restriction. Therefore, we studied these interactions using an obese diabetic animal model. KK-Ay mice were pair-fed normal chow [NC; carbohydrate: fat: protein = 65:15:20], low carbohydrate [LC; 43:42:15] or severely carbohydrate restricted diets [SR; 12:45:43] for 12 weeks...

Sodium-glucose cotransporter 2 inhibitor (SGLT2i)-associated euglycaemic diabetic ketoacidosis (euDKA) is a serious and increasingly recognised complication of treatment with this class of oral hypoglycaemic agents and can present a diagnostic challenge, resulting in delayed recognition, inappropriate treatment and potentially life-threatening acidosis. We present two cases of patients developing SGLT2i-associated euDKA in the early postoperative period. We support ceasing SGLT2i for 72 hours preoperatively and would suggest continuing to withhold the medication until oral intake is restored, and recommend a wider awareness of SGLT2i-associated diabetic ketoacidosis (DKA) amongst patients and their healthcare providers with an emphasis on checking ketone levels irrespective of blood glucose levels in the postoperative setting...

BACKGROUND AND AIMS: Leukocytosis, particularly monocytosis, has been shown to promote atherosclerosis in both diabetic and non-diabetic mouse models. We previously showed that hyperglycemia independently promotes monocytosis and impairs the resolution of atherosclerosis. Since patients with chronic diabetes often develop dyslipidemia and also have increased risk for atherosclerosis, we sought to examine how controlling blood glucose affects atherosclerosis development in the presence of severe hyperlipidemia...

In randomized controlled trials (RCTs), sodium-glucose co-transporter-2 (SGLT2) inhibitors have been shown to confer glycaemic and extra-glycaemic benefits. The DARWIN-T2D (DApagliflozin Real World evIdeNce in Type 2 Diabetes) study was a multicentre retrospective study designed to evaluate the baseline characteristics of patients receiving dapagliflozin vs those receiving selected comparators (dipeptidyl peptidase-4 inhibitors, gliclazide, or glucagon-like peptide-1 receptor agonists), and drug effectiveness in routine clinical practice...

We aimed to evaluate the comparative efficacy and safety of dipeptidyl peptidase-4 inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose co-transporter 2 inhibitors (SGLT2i), or thiazolidinedione (TZD) as an adjunctive treatment in patients with poorly controlled type 2 diabetes mellitus (T2DM) on insulin therapy. We searched Medline, Embase, the Cochrane Library, and ClinicalTrials.gov through April 2016. Bayesian network meta-analyses were performed with covariate adjustment...

Clinical and experimental studies have shown that sodium glucose co-transporter 2 inhibitors (SGLT2i) contribute to the prevention of diabetic kidney disease progression. In order to clarify its pharmacological effects on the molecular mechanisms underlying the development of diabetic kidney disease, we administered different doses of the SGLT2i, ipragliflozin, to type 2 diabetic mice. A high-dose ipragliflozin treatment for 8 weeks lowered blood glucose levels and reduced urinary albumin excretion. High- and low-dose ipragliflozin both inhibited renal and glomerular hypertrophy, and reduced NADPH oxidase 4 expression and subsequent oxidative stress...

BACKGROUND: The U.S. Food and Drug Administration recently issued a safety communication requiring new warnings of increased leg and foot amputation risk be added to canagliflozin drug labelling. However, the risk associated with other sodium-glucose co-transporter 2 inhibitors (SGLT2i) remains uncertain. AIM: This meta-analysis aimed to evaluate the potential risks of diabetic foot syndrome (DFS) and amputation associated with SGLT2i. METHODS: Relevant databases were searched from inception to June 14, 2017 to identify randomized controlled trials (RCTs) that evaluated risks of DFS and amputation associated with SGLT2i use...

Obstructive sleep apnea syndrome (OSAS) is often associated with metabolic disorders such as obesity and type 2 diabetes and may contribute to cardiovascular events. A novel class of antidiabetic drugs, the sodium glucose cotransporter 2 inhibitors (SGLT2i) reduce body weight (BW), although there is limited data on their impact on OSAS. We therefore evaluated the effect of SGLT2i on OSAS in patients with type 2 diabetes. The presented study was a retrospective design in 18 patients with type 2 diabetes with OSAS (4 males, age range 39-81 yr) administrated a SGLT2i...