J Clin Hypertens (Greenwich). 2011;00:00-00. ©2011 Wiley Periodicals, Inc. Both impaired glucose tolerance and diabetes are associated with substantially increased prevalence of hypertension, cardiovascular and renal disease. The goal for hypertension treatment in diabetic patients is in evolution, because of recent clinical trials. For example, the results of the recent ...

OBJECTIVE Gastric bypass (GB) surgery is associated with postprandial hyperinsulinemia, and this effect is accentuated in postsurgical patients who develop recurrent hypoglycemia. Plasma levels of the incretin glucagon-like peptide 1 (GLP-1) are dramatically increased after GB, suggesting that its action contributes to alteration in postprandial glucose regulation. The aim of ...

Background:  Interventions that preserve or increase β-cell mass may also prevent Type 2 diabetes. Rosiglitazone alone, as well as in combination with metformin, prevents diabetes in people with high, yet non-diabetic glucose levels. These effects may be mediated through changes in β-cell mass. In the present study, the effect of ...

Metformin has long been thought to cause lactic acidosis (LA) but evidence from various sources has led researchers to question a direct causative relationship. We assessed the relationship of metformin prescription and other factors to the incidence of LA. All cases of LA at a single hospital were identified from ...

We evaluated the impact of stopping medication for 2 days on reductions in the high intestinal FDG uptake induced by metformin. One hundred thirty-eight diabetic patients were divided into two groups: one in which the antihyperglycemic drug regimen included metformin (group A; n = 107) and one in which the ...

Functional effects of acute and prolonged (48 h) exposure to the biguanide drug metformin were examined in the clonal pancreatic β-cell line, BRIN-BD11. Effects of metformin on prolonged exposure to excessive increased concentrations of glucose and palmitic acid were also assessed. In acute 20-min incubations, 12.5-50 μm metformin did not ...

Insulin sensitizers are attractive candidate therapies for nonalcoholic steatohepatitis mainly because of the strong association between this disease and insulin resistance. This review provides a critical overview of the mechanisms of action, clinical trial results, and safety issues of metformin and glitazones in nonalcoholic steatohepatitis. It also highlights methodological challenges ...

To show that metformin, one of the most widely used agents, is contraindicated in patients with diabetes having chronic kidney disease (CKD) (i.e. serum creatinine >1.5 mg/dl) secondary to fear of lactic acidosis. The overall incidence of lactic acidosis is estimated at an upper limit of eight cases per 100 ...

Prolonged exposure of pancreatic beta-cells in vitro to the sulphonylureas tolbutamide and glibenclamide induces subsequent desensitization of insulinotropic pathways. Clinically, the insulin-sensitizing biguanide drug metformin is often administered alongside sulphonylurea as antidiabetic therapy. The present study examines the functional effects of metformin (200 µM) on tolbutamide- and glibenclamide-induced desensitisation. Acute ...

Vildagliptin (Galvus®, Jalra®, Xiliarx®) is an orally administered dipeptidyl peptidase-4 (DPP-4) inhibitor. In patients with type 2 diabetes mellitus, vildagliptin 50 mg twice daily is indicated for use in combination with metformin or a thiazolidinedione, and vildagliptin 50 mg once daily is indicated for use in combination with a sulfonylurea. A fixed-dose ...

Carnivorous fish species such as the rainbow trout (Oncorhynchus mykiss) are considered to be "glucose intolerant" because of the prolonged hyperglycemia experienced after intake of a carbohydrate-enriched meal. In the present study, we use this species to study glucose homeostasis in fish chronically infused with the hypoglycemic agents, insulin, and ...

To investigate the relationship between diabetes and metformin use with outcomes after radical prostatectomy (RP) for clinically localized cancer. A total of 112 diabetic metformin users and 98 diabetic non-metformin users treated with RP from 1990 to 2009 were identified. Nondiabetic controls were match using their 5-year risk of biochemical ...

The objective of this study was to compare the effects of gliclazide/metformin on glycemic control in patients with Type 2 diabetes mellitus uncontrolled on monotherapy with sulfonylurea or metformin. This was a prospective, open-labeled, multicentric study over 12 weeks. Patients who were diagnosed of Type 2 diabetes and were uncontrolled ...

To evaluate liraglutide as an antidiabetic agent. The pertinent English-language medical literature was reviewed for the period from 1985 to April 2010 with use of data from MEDLINE. Liraglutide is a glucagonlike peptide-1 receptor analogue that stimulates insulin secretion, reduces postprandial glucagon release, causes a mild delay in gastric emptying, ...

Lipotoxicity has recently been shown to be an important risk factor underlying the pathogenesis of pre-diabetes. However, clinical evidence supporting the treatment of pre-diabetes by improving lipotoxicity is lacking. Here, we conducted an open-label, randomized, controlled trial to investigate whether fenofibrate, the widely used hypolipidaemic agent, might benefit pre-diabetes, with ...

Type 2 diabetes (T2DM) is a multifaceted disease, characterized by hyperglycaemia, resulting from a combination of insulin resistance, impaired incretin action and β-cell dysfunction leading to relative insulin deficiency. Although traditional anti-diabetes agents improve hyperglycaemia, they do so at a cost, which may entail hypoglycemia and increased body weight; exacerbating ...

Vaspin, adiponectin and interleukin-6 (IL-6) constitute novel adipose-tissue derivatives, known as adipokines, which mediate insulin resistance. The aim of the present study was to evaluate the effects of metformin and rosiglitazone on serum levels of those novel adipokines in drug-naïve patients with type 2 diabetes mellitus (T2DM). 140 patients with ...

A 54-year-old obese woman with poorly controlled type 2 diabetes was put on the maximum allowed doses of Metformin, Glimepiride and Rosiglitazone. When Exenatide was added, she lost 33kg. She remained euglycemic for at least 7 months after the sequential discontinuation of Exenatide and the other oral agents.

Diabetes mellitus is a debilitating disease that is estimated to affect 366 million people by the year 2030. Type 2 diabetes mellitus (T2DM) is characterized by a progressive decline in pancreatic β-cell function and increased insulin resistance, and accounts for approximately 90% of people with diabetes. Oral antihyperglycaemic agents are ...

Osteoprotegerin (OPG) acts as an important regulatory molecule in atherosclerosis. Recent studies report that thiazolidinediones could affect OPG expression. We investigated the relationship between OPG and inflammatory cytokines and the effects of pioglitazone (a PPARγ (PPARG) agonist) versus metformin on serum OPG levels in type 2 diabetic patients. Sixty-seven type ...

Despite the common coexistence of diabetes and heart failure (HF), the optimal medial treatment of diabetes in HF patients has not been well studied. We sought to compare the association between metformin use and clinical outcomes in a cohort of ambulatory patients with diabetes and established HF. Using propensity score-matched ...

Type 2 diabetes mellitus (T2DM) and prediabetes (or patients at risk for diabetes) have been increasing in epidemic proportions. Dyslipidemia and hypertension are cardiovascular risk factors frequently associated with diabetes and prediabetes. Bile acid sequestrants (BAS) were initially approved for the treatment of elevated low-density lipoprotein cholesterol (LDL-C), but they ...

Metformin is widely used in clinic for handling the diabetic disorders. However, action mechanisms of metformin remain obscure. It has recently been indicated that guanidinium derivatives are ligands to activate type-2 imidazoline receptors (I-2 receptors) that can improve diabetes through increment in skeletal muscle glucose uptake. Also, activation of I-2 ...

To determine the effect of treatment with insulin aspart compared with NPH insulin, together with metformin/placebo and rosiglitazone/placebo. The hypothesis was that combined correction of major pathogenetic defects in type 2 diabetes would result in optimal glycemic control. This study was a 2-year investigator-driven randomized partly placebo-controlled multicenter trial in ...

We compared the combined use of basal insulin, metformin and insulin secretagogues with a combination of basal insulin and metformin in patients with type 2 diabetes starting basal insulin analogue therapy. This analysis was part of a 24-week trial, in which 964 insulin-naive patients with type 2 diabetes inadequately controlled ...

Type 2 diabetes is an increasingly prevalent disease resulting from various complex combinations of defects in insulin secretion and insulin action. Adequate blood glucose control is necessary to minimize complications. DPP IV inhibitors (sitagliptin, vildagliptin, saxagliptin) offer new options for combined pharmacological therapy. An extensive literature search was performed to ...

Clinical studies in Type 2 diabetes mellitus have shown that the effects of metformin go beyond improving HbA(1c) and include reductions in cardiovascular endpoints. Metformin therapy has been widely used in the treatment of Type 2 diabetes for many years, yet the precise mode of action remains uncertain. It has ...

OBJECTIVE: To evaluate the effects of a pill with drospirenone (3 mg) plus ethinyl E(2) (20 μg) (DRP/20EE) alone or associated with metformin or cyproterone acetate (CPA) on some metabolic cardiovascular risk factors in women with polycystic ovary syndrome (PCOS). DESIGN: Randomized, open-label clinical trial. SETTING: Academic medical clinic. PATIENT(S): ...

Dipeptidyl peptidase-4 inhibitors improve glycaemic control in patients with type 2 diabetes mellitus when used as monotherapy or in combination with other anti-diabetic drugs (metformin, sulphonylurea, or thiazolidinedione). This 18-week, phase 3b, multicentre, double-blind, noninferiority trial compared the efficacy and safety of two dipeptidyl peptidase-4 inhibitors, saxagliptin and sitagliptin, in ...

Non-alcoholic fatty liver disease generally has a benign course; however, patients with non-alcoholic steatohepatitis (NASH) may progress to cirrhosis and hepatocellular carcinoma. Currently, there is a lack of consensus about optimal NASH treatment. To assess the efficacy of insulin-sensitizing agents on histological and biochemical outcomes in randomized control trials of ...

There are different studies about the efficacy and safety and tolerability of thiazolidinediones added to metformin. The reported improved glycemic control with thiazolidinediones use seems to be associated with an increase in weight with an estimated 2-3kg weight gain suggesting that maybe thiazolidinediones are not safe for the clinical use. ...

The pharmacology, pharmacokinetics, efficacy, safety, and dosage and administration of saxagliptin are reviewed. Saxagliptin is a selective, reversible inhibitor of dipeptidyl peptidase-4 (DPP-4) approved for the treatment of type 2 diabetes mellitus in adults. By inhibiting DPP-4, saxagliptin reduces the degradation of endogenous incretin hormones, resulting in increased glucose-dependent insulin ...

The safety of metformin in heart failure has been questioned because of a perceived risk of life-threatening lactic acidosis, though recent studies have not supported this concern. We investigated the risk of all-cause mortality associated with individual glucose-lowering treatment regimens used in current clinical practice in Denmark. All patients aged ...

The mechanisms of metformin effects on glucose transport and metabolism were investigated in human adipocytes. Human preadipocytes obtained from surgical biopsies were differentiated in vitro into adipocytes and the effects of metformin on glucose uptake, glucose oxidation and the involved signaling pathways were analyzed. Metformin (1mM, 24h) increased glucose uptake ...

Patients with schizophrenia have a greater incidence of being overweight or obese compared with the general population. Such individuals are often treated with second-generation (atypical) antipsychotics (SGAs), which are associated with weight gain, dyslipidemia, and other metabolic derangements. As a result, frequent monitoring of weight and other metabolic parameters is ...

Lactic acidosis associated with metformin treatment is a rare but important adverse event, and unravelling the problem is critical. First, this potential event still influences treatment strategies in type 2 diabetes mellitus, particularly in the many patients at risk of kidney failure, in those presenting contraindications to metformin and in ...

Type 2 diabetes mellitus is a chronic, progressive disease that necessitates comprehensive and individualized patient treatment strategies. Daily glycemic measures, including measures of postprandial glucose and fasting plasma glucose levels, in combination with measures of glycated hemoglobin (HbA(1c)) levels may be a more reliable indicator of blood glucose control and ...

The range of oral hypoglycaemic agents (OHAs) has increased from one insulin sensitiser (metformin) and one class of insulin secretagogues (sulphonylureas) with the addition of further class of insulin secretagogues (glitinides), a further class of insulin sensitisers (glitazones) and two new classes: an alpha glycosidase inhibitor and glucagon-like peptide agents. ...

To report a case of idiosyncratic hepatotoxicity associated with metformin in the treatment of type 2 diabetes with nonalcoholic fatty liver disease (NAFLD). A 61-year-old obese man presented with jaundice, nausea, fatigue, and an unintentional weight loss 2 weeks following initiation of metformin. Laboratory findings revealed aminotransferase values 10-15 times ...

Diabetes and cancer are common conditions, and their co-diagnosis in the same individual is not infrequent. A link between the two conditions has been postulated for almost 80 years, but only in the past decade has significant epidemiological evidence been amassed to suggest that diabetes and cancer are associated, and ...

To assess the efficacy and tolerability of alogliptin plus pioglitazone for initial combination therapy in drug-naïve type 2 diabetic patients. This 26-week, double-blind, parallel-group study randomized 655 patients with inadequately controlled type 2 diabetes to four arms: 25 mg alogliptin (A25) q.d. monotherapy, 30 mg pioglitazone (P30) q.d. monotherapy, or ...

Genome-wide association studies have begun to elucidate the genetic architecture of type 2 diabetes. We examined whether single nucleotide polymorphisms (SNPs) identified through targeted complementary approaches affect diabetes incidence in the at-risk population of the Diabetes Prevention Program (DPP) and whether they influence a response to preventive interventions. We selected ...

OBJECTIVE: To examine the association between selected glucose-lowering medications and left ventricular (LV) diastolic function in patients with diabetes. DESIGN: Retrospective cohort study (years 2005-2008). METHODS: Echocardiograms of 242 patients with diabetes undergoing coronary angiography were analyzed. All patients had an LV ejection fraction (LVEF) ≥20% and were without atrial ...

IMPORTANCE OF THE FIELD: Type 2 diabetes is typically associated with insulin resistance and dysfunction of insulin-secreting pancreatic beta-cells. Addressing these defects often requires therapy with a combination of differently acting antidiabetic agents. A potential novel combination in development brings together the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin with the thiazolidinedione ...

Type 2 diabetes (T2DM) is a complex disease combining defects in insulin secretion and insulin action. New compounds have been developed for improving glucose-induced insulin secretion and glucose control, without inducing hypoglycaemia or weight gain. Dipeptidylpeptidase-4 (DPP-4) inhibitors are new oral glucose-lowering agents, so-called incretin enhancers, which may be used ...

OBJECTIVE: Pioglitazone treatment in type 2 diabetes mellitus produced significant improvements in glycaemic control, plasma lipids, blood pressure and inflammation. The aim of this study was to investigate the effect of pioglitazone on systolic and diastolic function in diabetic patients. METHODS AND RESULTS: Forty-nine diabetic patients were included in the ...

The remodelling of the adipose tissue by pioglitazone may be associated with the sustained therapeutic effects. We studied the effects of withdrawal of pioglitazone after 3-month treatment on glucose, lipid and high-molecular weight (HMW) adiponectin levels as well as liver function in patients with type 2 diabetes mellitus. Forty-nine Japanese ...

Pioglitazone is an oral antidiabetic agent that decreases insulin resistance in adipose tissue, liver and muscles. This action is mediated by its link to a nuclear receptor called peroxisome proliferator-activated receptor-gamma. By improving insulin sensitivity, hepatic glucose production decreases and glucose uptake increases in the peripheral tissues. Beyond these effects ...

Metformin lowers blood glucose by reducing hepatic glucose output, increasing insulin sensitivity and enhancing peripheral glucose uptake. Metformin is widely used in women with Type 2 diabetes of child-bearing age, many of whom become pregnant. Studies to date in Type 2 diabetes in pregnancy, gestational diabetes and polycystic ovarian syndrome ...

No previous studies have evaluated the long-term anti-atherosclerotic effects of pioglitazone in Asian patients with type 2 diabetes. Therefore, the present study investigated the protective effects of pioglitazone on the progression of carotid intima-media thickness (IMT), an established surrogate marker of cardiovascular events in Japanese type 2 diabetic patients without ...