Retraction notice to "Acarbose on insulin resistance after an oral fat load: a double-blind, placebo controlled study".

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The article is a substantial duplication of an earlier published paper by the same group of authors (below), to which no reference was made during the manuscript submission or review process: Acarbose actions on insulin resistance and inflammatory parameters during an oral fat load. Giuseppe Derosa, Pamela Maffioli, Ilaria Ferrari, Elena Fogari, Angela D'Angelo, Ilaria Palumbo, Sabrina Randazzo, Lucio Bianchi, Arrigo FG Cicero. European Journal of Pharmacology 651 (2011) 240-250. http://doi:10.1016/j.ejphar.2010.11.015. The authors had declared during the editorial process that the article had not been published or was under consideration elsewhere. The article is being retracted per journal policy and academic standards.

Enalapril/lercanidipine combination on markers of cardiovascular risk: a randomized study.

The aim of this study was to evaluate enalapril/lercanidipine combination effects on markers of cardiovascular risk stratification in hypertensive patients. A total of 359 patients were randomized to enalapril 20 mg, lercanidipine 10 mg, or enalapril/lercanidipine 20/10 mg fixed combination. We evaluated blood pressure (BP), fasting plasma glucose (FPG), lipid profile, lipoprotein(a) (Lp[a]), soluble receptor for advanced glycation end products (sRAGE), soluble CD40 ligand (sCD40 L), serum myeloperoxidase (MPO), high sensitivity C-reactive protein (Hs-CRP), and tumor necrosis factor-α (TNF-α). We recorded a decrease of BP in all groups, with the enalapril/lercanidipine combination being more effective in reducing BP compared with single monotherapies. Lipid profile or FPG were not affected by various treatments. Lercanidipine, but not enalapril, improved Lp(a) levels compared with baseline, with enalapril/lercanidipine having a greater effect on Lp(a) reduction. All treatments increased sRAGE levels, and decreased sCD40 L and MPO, even if enalapril/lercanidipine combination was more effective than single monotherapies. TNF-α and Hs-CRP were greater reduced by enalapril/lercanidipine combination compared with enalapril (P < .05 for both). The enalapril/lercanidipine fixed combination was more effective than single monotherapies in decreasing BP, but also in improving markers of cardiovascular risk stratification in hypertensive patients.

Vildagliptin compared to glimepiride on post-prandial lipemia and on insulin resistance in type 2 diabetic patients.

OBJECTIVES: To evaluate the effects of vildagliptin compared to glimepiride on glycemic control, insulin resistance and post-prandial lipemia. MATERIAL AND METHODS: 167 type 2 diabetic patients, not adequately controlled by metformin, were randomized to vildagliptin 50 mg twice a day or glimepiride 2 mg three times a day for 6 months, in a double blind, randomized clinical trial. We evaluated: body mass index (BMI), glycemic control, fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), fasting plasma proinsulin (FPPr), glucagon, lipid profile, resistin, retinol binding protein-4 (RBP-4), visfatin and vaspin. Furthermore, at the randomization and at the end of the study all patients underwent an euglycemic hyperinsulinemic clamp to evaluate M value and an oral fat load. RESULTS: Despite a similar decrease of glycated hemoglobin, there were an increase of body weight with glimepiride + metformin and a decrease with vildagliptin + metformin. Fasting plasma insulin increased with glimepiride + metformin, while it did not change with vildagliptin + metformin. Vildagliptin + metformin improved lipid profile. Regarding insulin sensitivity, vildagliptin + metformin increased M value. Resistin, RBP-4, vaspin and visfatin were decreased by vildagliptin + metformin, but in group to group comparison, only vaspin reduction resulted statistically significant. Vildagliptin + metformin reduced post-prandial lipemia and insulinemia compared to glimepiride + metformin. CONCLUSION: Vildagliptin, in addition to metformin, was more effective than glimepiride + metformin in reducing insulin resistance and post-prandial lipemia.

Sitagliptin added to previously taken antidiabetic agents on insulin resistance and lipid profile: a 2-year study evaluation.

The aim of this study was to evaluate whether the positive effects of sitagliptin on glycemic control and insulin resistance were maintained also after 2 years of therapy and whether sitagliptin could be effective also in improving lipid profile. In this randomized, double-blind, placebo-controlled trial, 205 patients with type 2 diabetes in therapy with different antidiabetic drugs were randomized to add sitagliptin 100 mg once a day or placebo to their current therapy. We evaluated at the baseline and after 6, 12, 18, and 24 months the following parameters: body mass index, glycated hemoglobin (HbA1c ), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (Tg). Sitagliptin, added to previously taken antidiabetic agents, proved to be effective in improving glycemic profile, reducing HbA1c by -17.5%, FPG by -12.7%, PPG by -20.5%. Regarding insulin resistance, sitagliptin decreased FPI by -8.3% and HOMA-IR by -20.0%, confirming that what have been already reported in short-term studies can be applied also after 2 years of treatment. Sitagliptin also reduced body weight by -4.3%. Our study also showed the positive effect of sitagliptin on lipid profile; in particular, sitagliptin decreased TC by -13.3%, LDL-C by -20.4%, and Tg by -32.3%, and also increased HDL-C by + 13.6%. Sitagliptin proved to be effective on glycemic profile and insulin resistance even after 2 years of therapy and to be effective in improving body weight and lipid profile.

Results from a 12 months, randomized, clinical trial comparing an olmesartan/amlodipine single pill combination to olmesartan and amlodipine monotherapies on blood pressure and inflammation.

AIM: Hypertension affects nearly 1 in 3 adults in the United States, and it is an important modifiable risk factor for coronary artery disease, heart failure, renal failure, and stroke. The aim of this study was to evaluate the effects of a fixed-dose olmesartan/amlodipine combination on blood pressure control, lipid profile, insulin sensitivity, and inflammation compared to singles monotherapies. METHODS: We randomized 276 hypertensive patients to olmesartan 20 mg, amlodipine 10mg or a single pill containing a fixed-dose olmesartan/amlodipine combination 20/5mg for 12 months. We evaluated: body weight, body mass index (BMI), systolic and diastolic blood pressure (SBP and DBP), fasting plasma glucose (FPG), fasting plasma insulin (FPI), lipid profile, omentin, chemerin, high sensitivity C-reactive protein (Hs-CRP). At baseline, and after 6 and 12 months, patients underwent an euglycemic, hyperinsulinemic clamp to assess insulin sensitivity (M value). RESULTS: Olmesartan/amlodipine combination was more effective than amlodipine or olmesartan in reducing blood pressure. Olmesartan/amlodipine combination, but not amlodipine, decreased FPG after 12 months. Olmesartan/amlodipine combination better decreased FPI and HOMA index and increased M value compared to olmesartan and amlodipine monotherapies. Olmesartan/amlodipine significantly decreased chemerin and omentin compared to olmesartan and amlodipine. CONCLUSION: Other than to be more effective in reducing blood pressure, olmesartan/amlodipine single pill combination gave also a major increase of insulin sensitivity and a decrease of inflammatory markers compared to single monotherapies.

Different aspects of sartan + calcium antagonist association compared to the single therapy on inflammation and metabolic parameters in hypertensive patients.

This study aims to evaluate the effects of an angiotensin receptor blocker (ARB)/calcium channel blocker combination on blood pressure control, lipid profile, insulin sensitivity, and inflammation markers. We randomized 276 hypertensive patients to olmesartan 20 mg, amlodipine 10 mg, or a single pill containing an olmesartan/amlodipine combination 20/5 mg for 12 months. We evaluated the following: body weight, systolic and diastolic blood pressure, fasting plasma glucose, fasting plasma insulin (FPI), M value, lipid profile, adiponectin (ADN), high sensitivity C-reactive protein (Hs-CRP), monocyte chemoattractant protein-1 (MCP-1), and macrophage migration inhibitory factor-1ß (MIP-1ß). Olmesartan/amlodipine combination better reduced blood pressure, FPI, homeostasis model assessment index, and increased M value and ADN compared to olmesartan and amlodipine monotherapies. Olmesartan/amlodipine significantly decreased Hs-CRP, MCP-1, and MIP-1ß. In this multicenter, randomized, double-blind, clinical study, ARB/calcium antagonist combination resulted to be more effective than single monotherapies in reducing blood pressure, in improving insulin sensitivity, and in reducing inflammation parameters in patients with stage I essential hypertension.

Variations in inflammatory biomarkers following the addition of sitagliptin in patients with type 2 diabetes not controlled with metformin.

OBJECTIVE: The effects of dipeptidyl peptidase-4 (DPP-4) inhibition on adipose tissue inflammation remain obscure. The aim of this study was to evaluate the effects of the addition of sitagliptin on the ß-cell function and various inflammatory biomarkers in type 2 diabetic patients. METHODS: After a run-in period of taking metformin, 178 diabetic patients with poor glycemic control were randomized to take sitagliptin at a dose of 100 mg once a day or a placebo in addition to metformin for 12 months. We evaluated the following parameters at three, six, nine and twelve months: body mass index (BMI), glycemic control, the homeostasis model assessment insulin resistance index (HOMA-IR), the homeostasis model assessment ß-cell function index (HOMA-ß), the proinsulin/fasting plasma insulin ratio (Pr/FPI ratio) and the levels of fasting plasma insulin (FPI), fasting plasma proinsulin (FPPr), C-peptide, glucagon, resistin, vaspin, omentin-1 and tumor necrosis factor-α (TNF-α). Before and twelve months after the addition of sitagliptin, the patients underwent combined euglycemic hyperinsulinemic and hyperglycemic clamping with subsequent arginine stimulation to assess insulin sensitivity and secretion. RESULTS: Treatment with sitagliptin + metformin was more effective than placebo + metformin in improving glycemic control, the HOMA-IR and the glucagon level and increasing the HOMA-ß and all ß-cell measurements after combined euglycemic hyperinsulinemic and hyperglycemic clamping with subsequent arginine stimulation. Regarding inflammatory biomarkers, sitagliptin + metformin more effectively reduced the levels of resistin, vaspin and omentin-1 than placebo + metformin. CONCLUSION: When treatment with metformin alone is not adequate for obtaining glycemic control, the addition of sitagliptin can be considered due to its actions in preserving the ß-cell function and reducing the levels of biomarkers of inflammation.

Effects of exenatide and metformin in combination on some adipocytokine levels: a comparison with metformin monotherapy.

The aim of this study was to evaluate the effects of exenatide on levels of serum adipocytokines and on ß-cell function. The study was conducted between 2008 and 2012. After a run-in period with metformin, 174 patients with type-2 diabetes were randomly distributed to either a group receiving exenatide at 10 µg twice daily, or a group receiving the placebo, for 12 months. We evaluated body mass index (BMI), blood pressure, glycemic control, lipid profile, fasting plasma insulin (FPI), HOMA-IR, HOMA-ß, fasting plasma proinsulin (FPPr), proinsulin : fasting plasma insulin ratio (Pr/FPI ratio), C-peptide, glucagon, retinol binding protein-4 (RBP-4), visfatin, omentin-1, and microalbuminuria. We used ELISA methods to assess the various parameters. Patients also underwent a combined euglycemic-hyperinsulinemic and hyperglycemic clamp, with subsequent arginine stimulation. After 12 months, a combination of exenatide and metformin produced a better decrease in body mass, BMI, glycemic control, FPI, FPPr, FPPr/FPI ratio, HOMA-IR, and glucagon level. Treatment with exenatide + metformin was superior to the placebo + metformin in increasing HOMA-ß, C-peptide, and ß-cell function. Significant negative correlations were found between M value, an index of insulin sensitivity, and measured adipocytokines. In conclusion, the combination of exenatide + metformin plays a role in improving some adipocytokine levels, and is better than metformin alone. The significant negative correlation between M value and measured adipocytokines is another confirmation of the positive effects linked to the improvement in insulin sensitivity.

Effects of canrenone in patients with metabolic syndrome.

BACKGROUND: Metabolic syndrome is becoming a common disease due to a rise in obesity rates among adults. OBJECTIVES: The aim was to evaluate the effects of canrenone compared to placebo on metabolic and inflammatory parameters in patients affected by metabolic syndrome. A total of 145 patients were treated with placebo or canrenone, 50 mg/day, for 3 months and then 50 mg b.i.d. till the end of the study. Blood pressure, body weight, body mass index, fasting plasma glucose (FPG), fasting plasma insulin, HOMA-IR, lipid profile, plasma aldosterone, brain natriuretic peptide, high-sensitivity C-reactive protein (Hs-CRP), tumor necrosis factor-α (TNF-α) and M value were evaluated. RESULTS: A decrease of blood pressure was observed in canrenone group compared to baseline; moreover, systolic blood pressure value recorded after 6 months of canrenone therapy was lower than the one recorded with placebo. Canrenone gave a significant decrease of FPI and HOMA index, and an increase of M value both compared to baseline and to placebo. Canrenone also decreased triglycerides and FPG was not observed with placebo. Canrenone also decreased plasma aldosterone, Hs-CRP and TNF-α compared to baseline and to placebo. CONCLUSION: Canrenone seems to be effective in reducing some factors involved in metabolic syndrome and in improving insulin-resistance and the inflammatory state observed in these patients.

Berberis aristata/Silybum marianum fixed combination on lipid profile and insulin secretion in dyslipidemic patients.

BACKGROUND: Relatively large number of dietary supplements and nutraceuticals have been studied for their supposed or demonstrated ability to reduce cholesterolemia in humans. OBJECTIVES: The aim of this study was to evaluate the efficacy as antihypercholesterolemic and insulin-sensitizing agent of a combination of Berberis aristata/Silybum marianum extract (Berberol®) in a sample of dyslipidemic patients. A total of 102 dyslipidemic subjects were enrolled. After a 6 months run-in period of diet and physical activity, the patients were randomized to placebo or Berberis aristata/Silybum marianum extract 588 mg/105 mg, twice a day for 3 months. Berberis aristata/Silybum marianum and placebo were then interrupted for 2 months (washout period), and then restarted for further 3 months. Anthropometric and metabolic parameters were assessed; moreover, all patients underwent a glucagon stimulation test. RESULTS: Berberis aristata/Silybum marianum reduced total cholesterol, triglycerides and low-density lipoprotein cholesterol and increased high-density lipoprotein cholesterol after 3 months from randomization and compared to placebo group. When Berberis aristata/Silybum marianum was interrupted, lipid profile worsened, and it improved again when nutraceutical combination was reintroduced. During the glucagon stimulation test, a higher increase of C-peptide levels and a lower increase in glycemia after the test with Berberis aristata/Silybum marianum compared to placebo, to baseline and to randomization were recorded. No patients had serious adverse events in both groups. CONCLUSION: Berberis aristata/Silybum marianum is effective and safe in improving lipid profile and insulin secretion in euglycemic dyslipidemic patients.

Evaluation of safety and efficacy of a fixed olmesartan/amlodipine combination therapy compared to single monotherapies.

BACKGROUND: Hypertension is known to be one of the main risk factors for cardiovascular disease. OBJECTIVES: To evaluate the safety and efficacy of a fixed olmesartan/amlodipine (Olme/Amlo) combination in improving blood pressure control, lipid profile, insulin sensitivity and some inflammatory and insulin resistance markers. Two hundred and seventy-six hypertensive patients were randomly assigned to olmesartan 20 mg, amlodipine 10 mg or a single pill containing an Olme/Amlo combination 20/5 mg for 12 months. We evaluated after 6 and 12 months: body weight, body mass index (BMI), systolic and diastolic blood pressure (SBP and DBP, respectively), fasting plasma glucose (FPG), fasting plasma insulin (FPI), lipid profile, vaspin, visfatin, interleukins 8 and 10 (IL-8 and IL-10, respectively). Patients also underwent an euglycemic, hyperinsulinemic clamp. RESULTS: Olme/Amlo combination was more effective in decreasing SBP, and DPB compared to single monotherapies after 12 months. Olme/Amlo combination, but not amlodipine, decreased FPG after 12 months. FPI and HOMA index were decreased, and M value increased by Olme/Amlo combination compared to olmesartan monotherapy, and to amlodipine monotherapy. Olme/Amlo significantly decreased IL-8 and IL-10 better than each monotherapy. CONCLUSIONS: Olme/Amlo single pill combination can be a safe and effective option to reduce blood pressure, improve insulin sensitivity and decrease inflammatory markers.

Variation in inflammatory markers and glycemic parameters after 12 months of exenatide plus metformin treatment compared with metformin alone: a randomized placebo-controlled trial.

STUDY OBJECTIVE: To evaluate the effects of exenatide on some inflammatory markers and to quantify the effect of exenatide on ß-cell function. DESIGN: A randomized, double-blind, placebo-controlled trial. SETTING: Seven hospitals in Italy. PATIENTS: A total of 174 white treatment-naive adults with type 2 diabetes and a glycated hemoglobin (HbA(1c)) level higher than 7.5%. INTERVENTION: After an open-label run-in period of 8 ± 2 months with metformin, patients were randomized to take exenatide (5 µg twice/day for the first 4 weeks, 10 µg twice/day thereafter) or a placebo volume equivalent for 12 months. MEASUREMENTS AND MAIN RESULTS: Body mass index, HbA(1c), fasting plasma glucose, postprandial plasma glucose, fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index, homeostasis model assessment ß-cell function index (HOMA-ß), fasting plasma proinsulin (FPPr), proinsulin-to-fasting plasma insulin ratio (Pr:FPI ratio), C-peptide, glucagon, vaspin, chemerin, and resistin were evaluated at baseline, at randomization, and at 3, 6, 9, and 12 months. Patients also underwent a combined euglycemic, hyperinsulinemic, and hyperglycemic clamp with subsequent arginine stimulation to assess insulin sensitivity and insulin secretion. HbA(1c) was significantly improved with exenatide plus metformin compared with placebo plus metformin. Exenatide plus metformin was also significantly more effective than placebo plus metformin in increasing HOMA-ß C-peptide, and all measures of ß-cell function after the euglycemic hyperinsulinemic and hyperglycemic clamp. We observed that exenatide plus metformin also reduced resistin compared with placebo plus metformin. No variations in vaspin and chemerin were noted in group-to-group comparisons. We observed a significant correlation between M value increase, an index of insulin sensitivity, and a decrease in inflammatory parameters in the exenatide plus metformin group. CONCLUSIONS: The combination of exenatide plus metformin was more effective than metformin alone in improving glycemic control, ß-cell function, and inflammatory parameters.

RETRACTED: Evaluation of the positive effects on insulin-resistance and ß-cell measurements of vildagliptin in addition to metformin in type 2 diabetic patients.

We evaluated the positive effects of vildagliptin in addition to metformin on glycemic control and ß-cell function in type 2 diabetic patients. One hundred and seventy-one type 2 diabetic patients were instructed to add vildaglipin 50mg twice a day or placebo to metformin for 12 months. Body mass index (BMI), glycemic control, fasting plasma insulin (FPI), HOMA-IR, HOMA-ß, fasting plasma proinsulin (FPPr), proinsulin/fasting plasma insulin ratio (Pr/FPI ratio), C-peptide, glucagon, vaspin, visfatin, and omentin-1 were evaluated. Before, and after 12 months since the addition of vildagliptin, patients underwent a combined euglycemic hyperinsulinemic and hyperglycemic clamp, with subsequent arginine stimulation. Vildagliptin+metformin were more effective than placebo+metformin in reducing body weight and BMI, glycemic control, HOMA-IR, glucagon and insulin resistance measurements. Vildagliptin+metformin gave also a better increase of HOMA-ß, and of all ß-cell parameters after the clamp. We also recorded a significant correlation between M value increase and the decrease of vaspin, visfatin, and omentin-1 obtained with vildagliptin+metformin. Vildagliptin, in addition to metformin, proved to be effective in improving ß-cell function and in reducing insulin resistance measurements.

Ultrasonography modifications of visceral and subcutaneous adipose tissue after pioglitazone or glibenclamide therapy combined with rosuvastatin in type 2 diabetic patients not well controlled by metformin.

AIM: To compare pioglitazone or glibenclamide alone and in combination with rosuvastatin on hepatic steatosis in type 2 diabetic patients. MATERIALS AND METHODS: After 3 months of metformin, patients were randomized to add pioglitazone 15 mg twice a day or glibenclamide 5 mg twice a day for 6 months, and then rosuvastatin 5 mg was added for other 6 months. Patients underwent an ultrasound examination for evaluation of steatosis degree, subcutaneous adipose tissue, and visceral adipose tissue diameter, an euglycemic hyperinsulinemic clamp, and blood sample collection for evaluation of glycemic control, fasting plasma insulin, lipid profile, adipocytokines at randomization, and after 6 and 12 months. RESULTS: Both pioglitazone and glibenclamide improved glycemic control. Pioglitazone reduced fasting plasma insulin, whereas glibenclamide increased it. Pioglitazone increased the glucose infusion rate compared with glibenclamide. Pioglitazone, but not glibenclamide, improved the lipid profile, and, when rosuvastatin was added, there was a greater improvement with pioglitazone and rosuvastatin. Adiponectin was increased by pioglitazone (+0.5 µg/ml), with a further increase (+0.4 µg/ml) when rosuvastatin was added. A significant decrease in leptin (-3.1 ng/ml) and interleukin-6 (-0.4 pg/ml) was found only with pioglitazone; a similar trend (-2.5 ng/ml and -0.3 pg/ml, respectively) was maintained after the addition of rosuvastatin.Rosuvastatin+pioglitazone decreased tumor necrosis factor-α (-0.3 ng/ml) and were superior to glibenclamide+rosuvastatin in reducing high-sensitivity C-reactive protein (-0.4 mg/l).Pioglitazone decreased ultrasound parameters, and the addition of rosuvastatin further decreased them both compared with randomization and glibenclamide. CONCLUSION: Pioglitazone was more effective than glibenclamide in improving inflammation and hepatic steatosis indices.

Adipocytokine levels in obese and non-obese subjects: an observational study.

We evaluated the levels of some inflammatory adipocytokines in 363 obese and 365 non-obese subjects. We measured: body mass index (BMI), waist circumference (WC), fasting plasma glucose, fasting plasma insulin (FPI), homeostasis model assessment (HOMA) index, blood pressure, lipid profile, retinol binding protein-4 (RBP-4), vaspin, omentin-1, leptin, interleukin-6 (IL-6), visfatin, resistin, adiponectin (ADN), adipsin, tumor necrosis factor-α (TNF-α), and high sensitivity C-reactive protein (Hs-CRP). We observed higher BMI, WC, FPI, HOMA index, TC, LDL-C, RBP-4, leptin, IL-6, adipsin, Hs-CRP, vaspin, resistin and TNF-α levels, and lower visfatin, and ADN levels in obese compared to non-obese subjects. Higher WC correlated with lower ADN and visfatin levels, and higher vaspin levels. Higher HOMA index correlated with higher resistin, adipsin, RBP-4, and leptin concentrations, while higher leptin levels correlated with higher TNF-α, Hs-CRP, and IL-6 concentration, and lower ADN values. We confirmed obese subjects' predisposition to develop dysmetabolic disease and hormonal dysfunctions.