1,721,219 research outputs found

    Role of SGLT2 inhibitors in the treatment of type 2 diabetes mellitus.

    Full text link
    In the last ten years, knowledge on pathophysiology of type 2 diabetes (T2DM) has significantly increased, with multiple failures (decreased incretin effect, increased lipolysis, increased glucagon secretion, neurotransmitters dysfunction) recognized as important contributors, together with decreased insulin secretion and reduced peripheral glucose uptake. As a consequence, the pharmacologic therapy of T2DM has been progressively enriched by several novel classes of drugs, trying to overcome these defects. The last, intriguing compounds come into the market are SGLT2 inhibitors, framing the kidney in a different scenario, not as site of a harmful disease complication, but rather as the means to correct hyperglycemia and fight the disease. This review aims to offer a short, updated overview of the role of these compounds in the treatment of T2DM, focusing on efficacy, ancillary albeit relevant clinical effects, safety, potential cardiovascular protection, positioning in common therapeutic algorithms

    Extra-glycaemic properties of empagliflozin

    No full text
    Type 2 diabetes is a complex and multifaceted disease requiring an individualized approach. A special attention, in treating the patients, should be devoted to the presence of comorbidities like overweight or obesity and arterial hypertension. Among the available anti-hyperglycaemic agents, several are associated with side effects like hypoglycaemia and weight gain. An increasing interest is reported in sodium-glucose co-transporter-2 inhibitors, a relatively novel class of glucose-lowering drugs that act independently of insulin, provide benefits beyond glucose-lowering actions and show a better tolerability compared with traditional medications for type 2 diabetes. This review tries to offer a balanced view on the main extra-glycaemic effects of empagliflozin, also mentioning clinical data obtained with other sodium-glucose co-transporter-2 inhibitors; the role of the proximal tubule in the pathophysiology of diabetic nephropathy and the potential nehroprotection exerted by this compound are also briefly discussed

    What should be the target blood pressure in elderly patients with diabetes?

    Full text link
    Hypertension is very common in elderly subjects with type 2 diabetes. The coexistence of hypertension and diabetes can be devastating to the cardiovascular system, and in these patients, tight blood pressure (BP) control is particularly beneficial. Little information is available regarding the target BP levels in elderly hypertensive patients with type 2 diabetes, and therefore extrapolation from data in the general population should be done. However, it is difficult to extrapolate from the general population to these frail individuals, who usually have isolated systolic hypertension, comorbidities, organ damage, cardiovascular disease, and renal failure and have a high rate of orthostatic and postprandial hypotension. On the basis of the available evidence, we provide arguments supporting the individualized approach in these patients. Target BP should be based on concomitant diseases, orthostatic BP changes, and the general condition of the patients. It is recommended to lower BP in the elderly patient with diabetes to 60 mmHg. In patients with coronary artery disease and in patients with orthostatic hypotension, excessive BP lowering should be avoided. In elderly hypertensive patients with diabetes, BP levels should be monitored closely in the sitting and the standing position, and the treatment should be tailored to prevent excessive fall in BP

    Antihypertensive treatment and multifactorial approach for renal protection in diabetes

    No full text
    Type 2 diabetes is reaching epidemic proportions throughout the world, representing the most common cause of ESRD. Early identification of renal impairment associated with diabetes and initiation of renoprotective therapy are imperative. High BP, dyslipidemia, long duration of diabetes, and poor glycemic control are important risk factors; their modification, renal function monitoring, and combined therapies are the current integrated approaches to treat patients with diabetic kidney disease. Strong evidence suggests that achieving target BP goals via inhibition of the renin-angiotensin-aldosterone system confers significant renal protection for diabetic patients. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers lower BP and reduce both the progression of renal damage and adverse cardiovascular events; some important renoprotective actions seem to be independent of the antihypertensive effect. Stringent quality of glycemic control is another key point to prevent onset of nephropathy or slow its progression. Evidence from basic research and clinical trials indicates that hypolipidemic drugs, mainly statins, contribute to modulate the progression of renal damage in diabetes; their use should be considered in any patient with diabetes. Smoking cessation may slow nephropathy progression; given the additional health benefits of stopping smoking, this advice is an important part of the strategy of diabetic nephropathy treatment and prevention. In conclusion, a target-driven, long-term, intensified intervention aimed at multiple risk factors should be recommended in patients with diabetes to preserve their kidney function

    Role of the P2X7 receptor in the pathogenesis of type 2 diabetes and its microvascular complications

    Full text link
    P2X7 receptors can be found in many tissues and organs, where they mediate several biological functions. This review summarizes the current knowledge about the role of this receptor in the pathogenesis of type 2 diabetes, in which the key clinical features are impaired insulin secretion and sensitivity, hyperglycemia, coexistence of other cardiovascular risk factors such as dyslipidemia and hypertension, and subclinical inflammation. The receptor modulates crucial pathways in the pancreatic islets (where it can either exert a trophic or detrimental action on β cells), and in the liver, in the adipose tissue and in the skeletal muscle, which are main sites of insulin resistance. P2X7 receptors also modulate a series of inflammatory responses that participate in the development of the microvascular complications of the disease. Potent and selective P2X7R blockers are available to be tested in Phase I/II clinical studies for the treatment of several chronic diseases, and it might be worthwhile to consider inclusion of patients with type 2 diabetes and its complications.</p

    Glucagon-Like Peptide-1 Receptor Agonists—Use in Clinical Practice

    No full text
    In the past 2 decades, eight glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been approved for the management of type 2 diabetes, each with its peculiar molecular structure, pharmacokinetics, and metabolic effects. Along with their marked glucose-lowering actions, which occur both at fasting and in the postprandial phase without an increased risk of hypoglycemia, GLP-1RAs have provided marked reductions in body weight and ancillary improvements in blood pressure and lipid profile. Recent cardiovascular outcome trials have established the benefits of GLP-1RAs on major cardiovascular events and all-cause mortality, independent of glucose control, with minor effects on preventing hospitalization for heart failure. Novel evidence is also emerging on the protection of GLP-1RAs against diabetic kidney disease, mainly preventing the onset of macroalbuminuria. Several mechanisms have been proposed to explain the cardiorenal protective properties of GLP-1RAs, which may be direct or mediated by additional hemodynamic and anti-inflammatory/antioxidant effects. With their favorable cardiometabolic properties and safety profile, GLP-1RAs may offer an ideal pharmacological option for the management of diabetic kidney disease. In this review, we discuss pharmacokinetic properties, glucometabolic effects, and cardioprotective actions of GLP-1RAs, highlighting the available evidence for a kidney protective role and the proposed mechanisms
    corecore