SGLT2i

The effect of a sodium glucose cotransporter 2 inhibitor (SGLT2i) in reducing heart failure hospitalization in the EMPA-REG OUTCOMES trial has raised the possibility of using these agents to treat established heart failure. We hypothesize that osmotic diuresis induced by SGLT2 inhibition, a distinctly different diuretic mechanism than other diuretic classes, results in greater electrolyte-free water clearance, and ultimately in greater fluid clearance from the interstitial fluid (IF) space than from the circulation, potentially resulting in congestion relief with minimal impact on blood volume, arterial filling, and organ perfusion...

Saxagliptin (a dipeptidyl peptidase-4 inhibitor, DPP-4i) and dapagliflozin (a sodium-glucose cotransporter type 2 inhibitor, SGLT2i) improve glucose control in type 2 diabetes (T2D) through different potentially complementary mechanisms, thus offering the opportunity for a combined therapy. Area covered: The characteristics of the saxagliptin/dapagliflozin combination are analysed, focusing on: 1) pharmacokinetic and pharmacodynamic properties; 2) efficacy and safety in phase III trials with concurrent and sequential add-on therapy; and 3) potential use in clinical practice, including in special populations (cardiovascular disease, heart failure, chronic kidney disease, elderly)...

Sodium-glucose co-transporter-2 inhibitors (SGLT2i) provide outstanding long-term cardiovascular and renal protection in high-risk patients with type 2 diabetes mellitus. Yet, despite encouraging renal safety outcomes reported in the EMPA-REG study, scattered reports suggest that there might be a risk for acute kidney injury (AKI), which may occasionally be fatal or might require renal replacement therapy. Reduced trans-glomerular pressure with a modest decline in kidney function, an inherent characteristic of SGLT2i therapy, conceivably forms the basis for the long-term renal protection, resembling agents that block the renin-angiotensin-aldosterone (RAAS) axis...

Context: Both type 2 diabetes (T2D) and osteoporosis are affected by aging and quite often co-exist. Furthermore, the fracture risk in patients with T2D is increased. The aim of this article is to review updated information on osteoporosis and fracture risk in patients with T2D, to discuss the effects of diabetes treatment on bone metabolism, as well as the effect of anti-osteoporotic medications on the incidence and control of T2D and to provide a personalized guide to the optimal management...

Hypertension is one of the most important comorbidities of diabetes, contributing significantly to death and disability and leads to macrovascular and microvascular complications. When assessing the medical priorities for patients with diabetes, treating hypertension should be a primary consideration. Practical approaches to hypertension in diabetes, including individualized targets are discussed, as per stage and complication of diabetes, according to current studies and guidelines. Angiotensin converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARBs) are the most effective drugs for treating hypertension in diabetes, in the absence of contraindications...

A favorable effect of an inhibitor of the sodium-glucose cotransporter 2 (SGLT2i) on mortality of diabetic patients was recently reported, although mechanisms underlying that effect remained unclear. Here, we examine SGLT2i effects on survival of diabetic mice and assess factors underlying these outcomes. To examine SGLT2i treatment effects in a model of severe diabetes, we fed genetically diabetic db/db mice a high-fat diet and then assessed outcomes including diabetic complications between SGLT2i TA-1887-treated and control mice...

AIMS: To examine the incidence of amputation in patients with type 2 diabetes mellitus (T2DM) treated with sodium glucose co-transporter 2 (SGLT2) inhibitors overall, and canagliflozin specifically, compared with non-SGLT2 inhibitor antihyperglycaemic agents (AHAs). MATERIALS AND METHODS: Patients with T2DM newly exposed to SGLT2 inhibitors or non-SGLT2 inhibitor AHAs were identified using the Truven MarketScan database. The incidence of below-knee lower extremity (BKLE) amputation was calculated for patients treated with SGLT2 inhibitors, canagliflozin, or non-SGLT2 inhibitor AHAs...

Aims Recent trials (EMPA-REG OUTCOME and Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results [LEADER]) have shown improved cardiovascular (CV) mortality with specific currently available glucose-lowering medications (empagliflozin and liraglutide, respectively), but were limited to selected patient populations. We sought to evaluate the current use and potential real-world impact of empagliflozin (and other sodium-glucose co-transporter 2 inhibitors [SGLT2is]) and liraglutide (and other glucagonlike peptide-1 receptor agonist [GLP-1 RAs]) among patients in the Diabetes Collaborative Registry (DCR)...

The main aim of the treatment of type 2 diabetes is overall control of cardiovascular risk factors. Almost 50% of patients with type 2 diabetes do not achieve glycaemic targets, and a much higher percentage do not achieve weight and blood pressure targets, despite the therapeutic arsenal that has appeared in the last decade for the treatment of this disease. In addition, antidiabetic secretatogues and insulin are associated with weight gain and an increased risk of hyperglycaemic episodes. Clinical practice guidelines recommend sodium-glucose cotransporter-2 inhibitors (SGLT2i) as an alternative in the same therapeutic step as the other options after initiation of metformin therapy...

Selectivity is the property of a drug to preferentially bind to a biological structure. Most drugs can bind and stimulate or inhibit more than one system. Therefore, it is important that they are selective for the intended site and that the doses used do not have effects on other sites, which could provoke adverse reactions. Selectivity is assessed through in vitro experiments on organs or isolated cells. If the aim is to compare drugs, the experiment should be conducted in the same tissue and with the same design...

Non-alcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver disease. NAFLD may evolve to non-alcoholic steatohepatitis (NASH), which is causally related to cirrhosis and cardiovascular disease (CVD) mortality. There is no generally accepted effective treatment for NAFLD/NASH. Chronic kidney disease (CKD) is relatively common and might co-exist with NAFLD/NASH, aggravate one another, and increase CVD risk. Common therapies could improve outcome. Potent statins at high doses, such as atorvastatin and rosuvastatin, ameliorate NAFLD/NASH and reduce the mortality rates by half as compared with those on the same statins but without liver disease...

Hyperglycemia associated with inflammation and oxidative stress is a major cause of vascular dysfunction and cardiovascular disease in diabetes. Recent data reports that a selective sodium-glucose co-transporter 2 inhibitor (SGLT2i), empagliflozin (Jardiance(®)), ameliorates glucotoxicity via excretion of excess glucose in urine (glucosuria) and significantly improves cardiovascular mortality in type 2 diabetes mellitus (T2DM). The overarching hypothesis is that hyperglycemia and glucotoxicity are upstream of all other complications seen in diabetes...

BACKGROUND: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) blocks reabsorption of glucose by inhibiting SGLT2 in kidney, promotes the renal excretion of glucose and improves blood glucose control without requiring insulin secretion. Anti-atherosclerotic effects of SGLT2is have not been fully elucidated until today. METHODS: We retrospectively picked up patients with type 2 diabetes who had been continuously prescribed SGLT2i for 3 months or more between April 2014 and December 2016 by a chart-based analysis, and compared metabolic parameters including coronary risk factors before the SGLT2i treatment with the data at 3 and 6 months after the SGLT2i treatment started...

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are an increasingly prescribed class of medication for type 2 diabetes mellitus. Euglycaemic diabetic ketoacidosis (euDKA) has been reported in association with SGLT2i use. Clinicians need to understand how to recognise and treat this complication. We describe three cases of euDKA in patients treated with SGLT2i.

AIMS: Diabetic ketoacidosis (DKA) associated with SGLT-2 inhibitors (SGLT-2i) is a possible adverse event. In fact, SGLT-2i are capable of stimulating the release of glucagon and ketone re-absorption in the renal tubuli, thus increasing the concentration of ketone bodies. METHODS: A Medline search for SGLT2i (dapagliflozin, empagliflozin, canagliflozin, ipragliflozin, ertugliflozin, luseogliflozin) was performed, collecting all randomized trials with a duration of treatment≥12weeks, enrolling patients with type 2 diabetes, and comparing a SGLT2i with placebo or other comparators...

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are increasingly used for the treatment of type 2 diabetes (T2D) and can improve glucose control also in type 1 diabetes (T1D). In May 2015, regulatory agencies issued a warning that SGLT2is may cause diabetic ketoacidosis (DKA). We report details on 2 new cases of SGLT2i-associated DKA and review the literature for similar cases within randomized controlled trials (RCTs), cohort studies and single reports. We searched the medical literature for reports of SGLT2i-associated DKA cases...

Obesity is a major cause of type 2 diabetes and may complicate type 1 diabetes. Weight loss for obese individuals with diabetes has many health benefits, often leads to improvement in glucose control and sometimes, in type 2 diabetes, near normalisation of abnormal glucose metabolism. Weight loss is difficult to maintain and attempts to lose weight may be undermined by some diabetes treatments such as sulfonylureas, thiazolidinediones and insulin. Whilst lifestyle support should be the primary approach to aid individuals who wish to lose weight, pharmacological approaches can also be considered...

AIMS/HYPOTHESIS: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are indicated for the treatment of type 2 diabetes and may also improve glucose control in type 1 diabetes. In 2015, regulatory agencies warned that SGLT2i may favour diabetic ketoacidosis (DKA). We provide a detailed analysis of DKA reports in which an SGLT2i was listed among suspect or concomitant drugs in the US Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: We first analysed the entire public FAERS up to September (third quarter [Q3]) 2016 to extract the number of reports, background indications and concomitant medications, and to calculate proportional reporting ratios (PRRs) and safety signals...

INTRODUCTION: Patients with type 2 diabetes have an increased risk of developing adverse cardiovascular (CV) outcomes. The evidence relating to the effects of glucose-lowering medications on CV outcomes is of variable quality and there are numerous trials ongoing. RESULTS: In this review, we summarise the available literature on CV outcomes of the following diabetes treatments: metformin, the sulfonylureas, acarbose, glucagon-like peptide 1 (GLP1) receptor agonists, dipeptidyl peptidase-4 inhibitors (DPP4i), sodium-glucose co-transporter 2 inhibitors (SGLT2i), thiazolidinediones (TZDs) and insulin...

AIMS: To estimate and compare incidence of diabetes ketoacidosis (DKA) among patients with type 2 diabetes who are newly treated with SGLT2 inhibitors (SGLT2i) versus non-SGLT2i antihyperglycemic agents (AHAs) in actual clinical practice. METHODS: A new-user cohort study design using a large insurance claims database in the US. DKA incidence was compared between new users of SGLT2i and new users of non-SGLT2i AHAs pair-matched on exposure propensity scores (EPS) using Cox regression models...