Comparison of effects of gliclazide, metformin and pioglitazone monotherapies on glycemic control and cardiovascular risk factors in patients with newly diagnosed uncontrolled type 2 diabetes mellitus. Efficacy of combination of Ezetimibe 10 mg and rosuvastatin 2.5 mg versus rosuvastatin 5 mg monotherapy for hypercholesterolemia in patients with type 2 diabetes Effects of Concomitant Administration of a Dipeptidyl Peptidase-4 Inhibitor in Japanese Patients with Type 2 Diabetes Showing Relatively Good Glycemic Control Under Treatment with a Sodium Glucose Co-Transporter 2 Inhibitor. Patients with Type 2 Diabetes Mellitus failing on oral agents and starting once daily insulin regimen; a small randomized study investigating effects of adding vildagliptin Effects of Extended-Release Niacin Added to Simvastatin/Ezetimibe on Glucose and Insulin Values in AIM-HIGH. Effect on glycemic control of the addition of 2.5 mg glipizide GITS to metformin in patients with T2DM. Efficacy of ezetimibe in patients with statin-resistant and statin-intolerant familial hyperlipidaemias Comparative Effectiveness of Dipeptidylpeptidase-4 Inhibitors in Type 2 Diabetes: A Systematic Review and Mixed Treatment Comparison The effect of simvastatin-ezetimibe combination therapy on adipose tissue hormones and systemic inflammation in patients with isolated hypercholesterolemia. Effect of vildagliptin on hsCRP and arterial stiffness in patients with type 2 diabetes mellitus Improved endothelial function with simvastatin but unchanged insulin sensitivity with simvastatin or ezetimibe. Usefulness of Nutraceuticals (Armolipid Plus) Versus Ezetimibe and Combination in Statin-Intolerant Patients With Dyslipidemia With Coronary Heart Disease. Double-blind randomized clinical trial of the effects of ezetimibe on postprandial hyperlipidaemia and hyperglycaemia. One-year outcome of a combination of weight loss therapies for subjects with type 2 diabetes: a randomized trial. Effects of metformin plus gliclazide versus metformin plus glimepiride on cardiovascular risk factors in patients with type 2 diabetes mellitus. Effects of Metformin in Patients with Poorly Controlled, Insulin-Treated Type 2 Diabetes Mellitus A randomised trial of three counselling strategies for lifestyle changes in patients with hypercholesterolemia treated with ezetimibe on top of statin therapy (TWICE).
OBJECTIVE The objective of this study was to evaluate and compare the effects of gliclazide-modified release ( gliclazide-MR ) , metformine ( MET ) and pioglitazone ( PIO ) monotherapies on glycemic control and conventional/non-conventional cardiovascular risk factors in patients with newly diagnosed type 2 diabetes mellitus ( T2DM ) . MATERIAL AND METHODS A single center , r and omized , 52-wk comparator-controlled clinical study was carried out in patients with newly diagnosed uncontrolled T2DM . A total of 57 patients were r and omized into gliclazide-MR , metformin and pioglitazone groups . Drugs were administered for 12 months . Anthropometric measurements , fasting plasma glucose ( FPG ) , postpr and ial plasma glucose ( PPG ) , HbA1c , insulin , HOMA-IR , lipid parameters , the markers of coagulation/fibrinolysis , inflammation and endothelial dysfunction were measured at baseline and at months 3 , 6 , and 12 . RESULTS In the gliclazide-MR group , HC , FPG , HbA1c , insulin , HOMA-IR , TC , trigylcerides , Lp ( a ) , E-selectin and Hcy were significantly decreased after treatment compared to baseline . In the MET group , BMI , WC , FPG , PPG , HbA1c , ICAM-1 and Hcy significantly decreased after treatment compared to baseline . In PIO group , WC , HC , FPG , PPG , HbA1c , C-peptid , HOMA-IR , trigylcerides , vWF , IL-6 , ICAM-1 , E-selectin and Hcy significantly decreased after treatment compared to baseline , whereas , HDL-C increased . At the end of the month 12 , the decreases in insulin and HOMA-IR score were more pronounced with PIO compared to gliclazide . CONCLUSIONS Gliclazide-MR , MET and PIO monotherapies , were equally effective in proving glycemic control in patients with newly diagnosed , oral antidiabetic (OAD)-naive T2DM . But , improvements in conventional/non-conventional cardiovascular risk factors were more pronounced in patients on PIO therapy compared to gliclazide and MET therapies . Also , all of the 3 drugs represent effective and safe first-line pharmacological treatment options in these patients Background Statins are used to treat hypercholesterolemia in patients with type 2 diabetes mellitus , but many of these patients fail to achieve the target LDL-C level . Recent reports have suggested that a synergistic effect can be obtained by concomitant administration of the cholesterol absorption inhibitor ezetimibe and a statin . However , in patients with type 2 diabetes who are already being treated with satins , it remains unclear whether it is more effective to add ezetimibe or to increase the statin dose . Therefore , this study was performed to examine the effects of these two regimens on LDL-C and lipoproteins . Methods The subjects were type 2 diabetic patients under treatment with rosuvastatin ( 2.5 mg daily ) , who had LDL-C levels ≥80 mg/dL. They were r and omly allocated to a group that received add-on therapy with ezetimibe at 10 mg/day ( combination group , n = 40 ) or an increase of the rosuvastatin dose to 5 mg/day ( dose escalation group , n = 39 ) . These two groups were compared at baseline and after 12 weeks of treatment . Results The percent change of LDL-C was −31 % in the combination group and −12 % in the dose escalation group . Both groups showed a significant decrease , but the decrease was greater in the combination group . In both groups , there was a significant decrease in the levels of small dense LDL-C , oxidized LDL and remnant-like lipoprotein cholesterol . For all of these parameters , the percent changes were greater in the combination group . Only the combination group showed a significant decrease of triglycerides . Multivariate analysis was performed to identify factors associated with reaching an LDL-C level < 80 mg/dL. As a result , add-on therapy with ezetimibe was extracted as a factor related to improvement of LDL-C. Conclusions Compared with increasing the dose of rosuvastatin , the combination of rosuvastatin and ezetimibe not only achieves quantitative but also qualitative improvement of serum lipid levels in type 2 diabetic patients , suggesting that this combination could suppress the progression of atherosclerosis . Trial registration We conducted this study to determine whether additional administration of a dipeptidyl peptidase-4 ( DPP-4 ) inhibitor might provide further improvement of the glycemic control in Japanese type 2 diabetes patients showing relatively good glycemic control under treatment with a sodium glucose co-transporter 2 ( SGLT2 ) inhibitor . Five SGLT2 inhibitor ( luseogliflozin , dapagliflozin , tofogliflozin , empagliflozin and canagliflozin ) preparations and five DPP-4 inhibitor ( sitagliptin , vildagliptin , alogliptin , anagliptin and linagliptin ) preparations were used . The results showed that monotherapy with SGLT2 inhibitor produced significant decreases of the body weight and BMI , hemoglobin A1c ( HbA1c ) also decreased , but not to a significant extent . However , decreases of the serum aspartate aminotransferase ( AST ) , alanine aminotransferase ( ALT ) , γ-glutamyltransferase ( γ-GTP ) and uric acid were observed in this group . On the other h and , in type 2 diabetes patients treated concomitantly with a DPP-4 inhibitor and SGLT2 inhibitor , significant decrease of the HbA1c was observed , indicating the favorable effect of the concomitant therapy . The body weight and BMI decreased . As for the serum lipid profile , elevation of the serum HDL-cholesterol ( HDL-C ) was observed . Furthermore , AST , ALT , γ-GTP and uric acid decreased in the combined treatment group . Then , the therapeutic responses to concurrent administration with SGLT2 inhibitor of each of the 5 individual DPP-4 inhibitors used in this study were analyzed . The results showed that concomitant administration of sitagliptin , a DPP-4 inhibitor , with the SGLT2 inhibitor yielded the best results in terms of the lowering of the HbA1c and improvement of the serum lipid profile Background The addition of a DDP4-inhibitor to existing insulin therapy reduces HbA1c . However , no data exist about the addition of these agents at the beginning of insulin treatment in type 2 diabetes while this could especially be interesting because it is during this period that considerable residual beta cell function is still present . The benefit of such a strategy could be a lower insulin dose required for glycemic control . The hypothesis of our study was that adding a DPP4-inhibitor at the beginning of insulin treatment could lead to less exogenous insulin requirement , a reduction of hyperinsulinemia and side effects ( hypoglycemia and weight gain ) , less glucose variability and improvement of insulin and glucagon dynamics during a mixed meal test . Results In this small clinical trial ( trial registration NTR2022 ) 9 patients were r and omized to receive  vildagliptin  and 6 to receive placebo in addition to start of once daily insulin treatment . Unfortunately , due to a difficult inclusion , the preset sample size of 40 patients could not be met . Median units of insulin at the end of the study was 47 U in the placebo group and 34 U in the vildagliptin group . Median glycemic variability ( SD ) at the end of study was 2.1 in the placebo group and 1.5 in the vildagliptin group . Median weight gain at the end of study was 3 kg in the placebo and 0.5 kg in the vildagliptin group . Occurrence of hypoglycemia was low in both groups . Insulin , C-peptide , glucose and glucagon levels were comparable during mixed meal tests . Conclusions This small r and omized study did not have sufficient power to detect effects of the addition of vildagliptin to the start of once daily long-acting insulin . However in our opinion adding a DPP4-inhibitor , especially in this group remains a very interesting approach . This study could be used as a guidance for larger studies that are required to investigate the effects of this intervention on insulin requirements , glycemic variability , hypoglycemia and weight gain BACKGROUND Niacin is an antidyslipidemic agent that may cause blood sugar elevation in patients with diabetes , but its effects on glucose and insulin values in nondiabetic statin-treated subjects with cardiovascular disease and at high risk for diabetes are less well known . METHODS This was a prespecified , intent-to-treat analysis of the Atherothrombosis Intervention in Metabolic syndrome with low high-density lipoprotein/high triglycerides : Impact on Global Health outcomes trial which r and omized 3,414 participants at 92 centers in the US and Canada to extended-release niacin ( ERN ) plus simvastatin/ezetimibe ( ERN ) or simvastatin/ezetimibe plus placebo ( Placebo ) . Baseline and annual fasting glucose and insulin values were measured . Those experiencing an adverse event indicative of diabetes or starting medications for diabetes were considered to have confirmed diabetes . In addition , nondiabetic subjects with 2 annual follow-up glucose measurements were categorized into normal , impaired fasting glucose or newly diagnosed diabetes ( presumed or confirmed ) states . RESULTS Compared with placebo , ERN increased annual fasting glucose from baseline to 1 year in both those with normal ( 7.9 ± 15.8 vs 4.3 ± 10.3 mg/dL ; P < .001 ) and impaired fasting glucose ( 4.1 ± 18.7 vs 1.4 ± 14.9 ; P < .02 ) and increased insulin levels . Both effects waned over the next 2 years . There were less consistent effects in those with baseline diabetes . There was an increased risk of progressing from normal to presumed or confirmed impaired fasting glucose ( ERN 197/336 ) cases ( 58.6 % ) vs placebo 135/325 cases ( 41.5 % ; P < .001 ) over time , but no difference in diabetes development in the 2 treatment groups except in those with normal fasting glucose at baseline . CONCLUSIONS The addition of ERN to simvastatin/ezetimibe had marginal effects on glycemia in those with diabetes at baseline , and there was a trend toward increased development of new-onset diabetes . In addition , ERN increased the risk of developing impaired fasting glucose , which may have deleterious consequences over time and warrants further study AIMS This study evaluated the effects on glycemic control of the addition of 2.5 mg glipizide GITS to metformin in patients with mild-to-moderate , but suboptimally controlled type 2 diabetes . METHODS In this multicenter , double-blind , placebo-controlled study , 122 patients with type 2 diabetes inadequately controlled ( A1c 7 - 8.5 % ) on metformin ( > or = 1000 mg/day for > or =3 months ) were r and omized to 16 weeks treatment with 2.5 mg/day glipizide GITS ( n=61 ) or placebo ( n=61 ) , in addition to their current metformin dose . The primary efficacy variable was the change in A1c from baseline to endpoint . Changes in fasting plasma glucose ( FPG ) , insulin concentrations , lipid profile and safety variables were also measured . RESULTS The addition of glipizide GITS to metformin gave significantly greater improvements in mean A1c and FPG from baseline to endpoint than placebo addition ( p<0.0002 ) . Significantly more patients in the glipizide GITS group than in the placebo group achieved the target A1c level of A1c<7.0 % ( p<0.0001 ) and an A1c<6.5 % ( p<0.0033 ) . Fasting insulin concentrations were similar in both groups and unchanged by treatment . Addition of glipizide GITS to metformin did not produce any significant or clinical ly relevant weight gain or changes in BMI . Both treatment regimens were well tolerated . CONCLUSIONS This study showed that the addition of 2.5 mg glipizide GITS to metformin significantly improved glucose control in patients with type 2 diabetes inadequately controlled by metformin monotherapy ABSTRACT Objective : To investigate the efficacy of the cholesterol absorption inhibitor ezetimibe in patients with refractory familial hyperlipidaemia or intolerant to statin therapy . Methods : This prospect i ve study assessed the safety and efficacy of ezetimibe in 200 patients with refractory familial hyperlipidaemias not achieving a low-density-lipoprotein ( LDL ) cholesterol < 3 mmol/L ( 116 mg/dL ) including 22 % intolerant to all statin therapy , many consuming sterol-containing products . Results : Ezetimibe monotherapy result ed in 7 % and 11 % reductions in LDL-cholesterol and apolipoprotein B respectively . Ezetimibe-statin combination therapy  reduced LDL-cholesterol by an additional 11 ± 27 % and apolipoprotein B by 11 ( + 79 to –18)% . There was a similar response between various sub-groups but a wide variation within groups with the greatest effect seen in patients under-responding to statins . The number of patients achieving the LDL‐C target of 3 mmol/L rose from 5.5 % to 18 % . Non-significant effects included a 5 ( + 78 to –470)% reduction in triglycerides , 8 ± 36 % increment in HDL‐cholesterol , 21 ( + 35 to –82)% reduction in C-reactive protein and a 1 ( + 20 to –50)% increase in alanine transaminase . No effects were seen on creatinine , creatine kinase , or insulin resistance . Fourteen patients ( 7 % ) discontinued ezetimibe : seven due to gastrointestinal side-effects , one patient developed an ezetimibe-induced hypercholesterolaemia ( × 1.5 ) , one developed ezetimibe-induced hypertriglyceridaemia ( × 7 ) and five discontinued for other reasons . Conclusion : Ezetimibe is a useful addition to statins in patients with familial hyperlipidaemias but shows a highly variable response profile Objective To compare the safety and efficacy of the dipeptidylpeptidase-4 ( DPP-4 ) inhibitors in patients with type 2 diabetes and inadequate glycemic control . Design Systematic review of r and omized controlled trials ( RCTs ) , health economic evaluation studies , systematic review s , and meta-analyses , followed by primary Bayesian mixed treatment comparison meta-analyses ( MTCs ) , and secondary frequentist direct-comparison meta-analyses using a r and om-effects model . Outcomes were reported as weighted mean change from baseline , or odds ratio ( OR ) with 95 % credible interval . Data sources MEDLINE , MEDLINE In-Process , EMBASE , and BIOSIS via Dialog ProQuest ; Cochrane Central Register of Controlled Trials and Cochrane Data base of Systematic Review s via EBSCO ; four diabetes and two technical congress abstract s ; and health technology assessment organization websites . Eligibility criteria Patients with type 2 diabetes and inadequate glycemic control receiving any pharmacological anti-diabetic treatment . Data extraction and analysis Title/ abstract s were review ed for eligibility , followed by full-text review of publications remaining after first pass . A three-person team filtered articles and an independent review er checked a r and om selection ( 10 % ) of filtered articles . Data extraction and quality assessment of studies were also independently review ed . Five DPP-4 inhibitors ( alogliptin , linagliptin , saxagliptin , sitagliptin , and vildagliptin ) were compared via meta- analysis ( where data were available ) as monotherapy , dual therapy ( plus metformin , sulfonylurea , pioglitazone , or insulin ) , and triple therapy ( plus metformin/sulfonylurea ) . Results The review identified 6,601 articles ; 163 met inclusion criteria and 85 publications from 83 RCTs contained sufficient or appropriate data for analysis . MTCs demonstrated no differences between DPP-4 inhibitors in mean change from baseline in glycosylated hemoglobin ( HbA1c ) or body weight , or the proportions of patients achieving HbA1c < 7 % or experiencing a hypoglycemic event , apart from in patients on alogliptin plus metformin , who achieved HbA1c < 7 % more frequently than those treated with saxagliptin plus metformin [ OR 6.41 ( 95 % CI 3.15–11.98 ) versus 2.17 ( 95 % CI 1.56–2.95 ) ] . Conclusions This systematic review and MTC showed similar efficacy and safety for DPP-4 inhibitors as treatment for type 2 diabetes , either as monotherapy or combination therapy BACKGROUND Pleiotropic effects of ezetimibe have only been investigated in a few studies . The aim of this article was to compare the effects of simvastatin and the combined treatment with simvastatin and ezetimibe on low- grade systemic inflammation and plasma levels of selected adipokines in patients with isolated hypercholesterolemia . METHODS The study included 69 patients with elevated cholesterol levels , who were allocated to one of the three groups treated for 12 weeks , respectively , with simvastatin ( 40 mg daily ) , simvastatin ( 40 mg daily ) plus ezetimibe ( 10 mg daily ) , or placebo .  Plasma levels of lipids , apolipoproteins , glucose homeostasis markers , leptin , adiponectin , visfatin , tumor necrosis factor-α ( TNF-α ) , free fatty acids ( FFA ) , and high-sensitive C-reactive protein ( hsCRP ) were determined on the allocation day and after 12 weeks of therapy . RESULTS Apart from improving lipid profile , simvastatin administered alone or in combination with ezetimibe , decreased plasma levels of hsCRP , FFA , leptin , visfatin , and TNF-α , as well as increased plasma levels of adiponectin . The combination therapy was superior to simvastatin in influencing plasma lipids/lipoproteins , hsCRP , FFA , and the investigated adipokines . The effect of the combination therapy , but not of simvastatin , on systemic inflammation and plasma adipokines was stronger in insulin-resistant than in insulin-sensitive subjects . CONCLUSIONS The obtained results suggest that insulin-resistant patients with hypercholesterolemia and high cardiovascular risk may benefit the most from the combined treatment with simvastatin and ezetimibe OBJECTIVE : To evaluate the effect of dipeptidyl-peptidase-4 ( DPP-4 ) inhibitor vildagliptin on high sensitivity C-reactive protein ( hsCRP ) and arterial stiffness ( AS ) in patients with type 2 diabetes ( T2DM ) . DESIGN : Sixty-four drug-naive diabetic patients , with inadequate glycemic control , participated in this r and omized , open-label study . Half of the patients received metformin 1700 mg/d and the other half of them received metformin 1700 mg/d plus vildagliptin 100 mg/d . AS was measured by carotid-femoral Pulse Wave Velocity ( cfPWV ) . Body weight ( BW ) , body mass index ( BMI ) , blood pressure ( BP ) , hsCRP , glycosylated hemoglobin ( HbA1c ) , fasting plasma glucose ( FPG ) , lipid profile , albumin/creatinine ratio ( ACR ) , fasting insulin , C-peptide , homeostasis model assessment of insulin resistance ( HOMA-IR ) and homeostasis model assessment of β-cell function ( HOMA-β ) were also assessed at baseline and after 6 months . RESULTS : Vildagliptin in combination with metformin had a beneficial influence on hsCRP , HbA1c , C-peptide and HOMA-β index ( p < 0.05 ) but had no effect on cfPWV , BP , BW , BMI , lipid profile , ACR and HOMA-IR compared with metformin alone ( p = NS ) . CONCLUSIONS : We have found that the addition of vildagliptin to metformin for a period of six months decreased hsCRP , improved glycemic control and β-cell function but had no effect on AS in drug-naive patients with T2DM In addition to their expected effects on lipid profile , lipid-lowering agents may reduce cardiovascular events because of effects on nonclassic risk factors such as insulin resistance and inflammation . Ezetimibe specifically blocks the absorption of dietary and biliary cholesterol as well as plant sterols . Although it is known that an additional reduction of low-density lipoprotein cholesterol ( LDL-C ) levels can be induced by the combination of ezetimibe with statins , it is not known if this can enhance some pleiotropic effects , which may be useful in slowing the atherosclerotic process . This study assessed the effects of simvastatin and ezetimibe , in monotherapy or in combination , on markers of endothelial function and insulin sensitivity . Fifty prediabetic subjects with normo- or mild-to-moderate hypercholesterolemia were r and omly allocated to 2 groups receiving either ezetimibe ( 10 mg/d ) or simvastatin ( 20 mg/d ) for 12 weeks , after which the drugs were combined for both groups for an additional 12-week period . Clinical and laboratory parameters were measured at baseline and after 12 and 24 weeks of therapy . Homeostasis model assessment of insulin resistance index and the area under the curve of insulin were calculated . As expected , both groups receiving drugs in isolation significantly reduced total cholesterol , LDL-C , apolipoprotein B , and triglyceride levels ; and additional reductions were found after the combination period ( P < .05 ) . After 12 weeks of monotherapy , plasminogen activator inhibitor-1 levels and urinary albumin excretion were lower in the simvastatin than in the ezetimibe group . No change in homeostasis model assessment of insulin resistance index , area under the curve of insulin , and adiponectin levels was observed after either the monotherapies or the combined therapy . However , simvastatin combined with ezetimibe provoked significant reductions in E-selectin and intravascular cellular adhesion molecule-1 levels that were independent of LDL-C changes . Our findings support cl aims that simvastatin may be beneficial in preserving endothelial function in prediabetic subjects with normo- or mild-to-moderate hypercholesterolemia . Alternatively , a deleterious effect of ezetimibe on the endothelial function is suggested , considering the increase in intravascular cellular adhesion molecule-1 and E-selectin levels .  Simvastatin and ezetimibe , in isolation or in combination , do not interfere with insulin sensitivity Statins are extensively used to treat dyslipidemia , but , because of their low tolerability profile , they are discontinued in a significant proportion of patients . Ezetimibe and nutraceuticals have been introduced as alternative therapies and have proved to be effective and well tolerated . A single-blind , single-center , r and omized , prospect i ve , and parallel group trial comparing a combination of nutraceuticals ( red yeast rice , policosanol , berberine , folic acid , coenzyme Q10 and astaxanthin ) , called Armolipid Plus , and ezetimibe for 3 months in terms of efficacy and tolerability . Patients who did not achieve their therapeutic target ( low-density lipoprotein cholesterol < 100 mg/dl ) could add the alternative treatment on top of r and omized treatment for another 12 months : 100 patients who are dyslipidemic with ischemic heart disease treated with percutaneous coronary intervention were enrolled ( ezetimibe n = 50 , nutraceutical n = 50 ) . Efficacy ( lipid profile ) and tolerability ( adverse events , transaminases , and creatine kinase ) were assessed after 3 and 12 months . After 3 months , 14 patients in the nutraceutical group achieved their therapeutic target , whereas none of the patients in the ezetimibe group did . At 1-year follow-up , 58 patients ( 72.5 % ) of the combined therapy group ( n = 86 ) and 14 ( 100 % ) of the nutraceutical group reached the therapeutic goal . No patients experienced important undesirable effects . In conclusion , nutraceuticals alone or in combination with ezetimibe are well tolerated and improve the lipid profile in statin-intolerant patients with coronary heart disease . Further studies are needed to assess long-term effects of nutraceuticals on mortality AIM Ezetimibe selectively blocks intestinal cholesterol absorption by inhibiting Niemann-Pick C1-like 1 ( NPC1L1 ) and reducing LDL cholesterol ( LDL-C ) . In animals , ezetimibe reversed diet-induced obesity , liver steatosis , and insulin resistance . In humans , its potential effects on liver steatosis and insulin resistance have been suggested . We investigated the effects of ezetimibe on postpr and ial hyperlipidaemia and hyperglycaemia in obese subjects with dyslipidaemia in a double-blind r and omized crossover trial . METHODS Twenty obese men with hypertriglyceridaemia were assigned r and omly to an ezetimibe- or a placebo-precedence-treated group . Subjects in the ezetimibe group were treated with ezetimibe ( 10 mg/day ) for the first 4 weeks , followed by a 4-week interval and then treated with placebo for another 4 weeks . The placebo group received these treatments in reverse order . Subjects were requested to fast for at least 12 hours and then received a st and ard meal . Blood sample s were collected at 0 , 30 , 60 , 120 , 240 , 360 and 480 minutes after the meal on Days 0 , 28 , 56 and 84 and were used to measure the lipid and glucose metabolism markers . RESULTS Ezetimibe significantly decreased the postpr and ial serum triglyceride excursion ( p=0.01 ) and fasting serum LDL-C , remnant-like particles(RLP ) and ApoB48 levels ( p<0.05 ) . Postpr and ial glucose excursion , serum insulin levels , serum glucose-dependent insulinotropic polypeptide ( GIP ) and active glucagon-like peptide-1 ( GLP-1 ) were not significantly affected by ezetimibe treatment . CONCLUSION Ezetimibe restored the postpr and ial dysregulation of lipid but did not affect glucose metabolism in a double-blind r and omized crossover trial OBJECTIVE The purpose of this study was to evaluate the effects of a combination weight loss program using intermittent low-calorie diets , energy-controlled meal replacement products , and sibutramine on weight loss , diabetes control , and cardiovascular risk factors in overweight or obese subjects with type 2 diabetes . RESEARCH DESIGN AND METHODS Overweight or obese individuals with type 2 diabetes treated with diet or oral medication were r and omly assigned to either a st and ard therapy or combination therapy group . Both groups received a st and ardized program to facilitate weight loss . The combination therapy group also received 10 - 15 mg sibutramine daily , low-calorie diets using meal replacement products for 1 week every 2 months , and between low-calorie diet weeks , once daily use of meal replacement product and snack bars to replace one usual meal and snack . Primary outcome measures were changes in body weight , glycemic control , plasma lipids , blood pressure , pulse , and body composition at 1 year . RESULTS At 1 year , combination therapy , compared with st and ard therapy , result ed in significantly more weight loss ( -7.3 + /- 1.3 kg vs. -0.8 + /- 0.9 kg , P < 0.001 ) and reduction in HbA(1c ) ( -0.6 + /- 0.3 vs. 0.0 + /- 0.2 % , P = 0.05 ) . Combination therapy result ed in reduced requirement for diabetes medications and decreased fat mass and lean body mass . A 5-kg decrease in weight at 1 year was associated with a decrease of 0.4 % in HbA(1c ) ( P = 0.006 ) . Changes in fasting glucose , lipids , pulse , and blood pressure did not differ between groups . CONCLUSIONS This combination weight loss  program result ed in greater weight loss and improved diabetes control compared with a st and ard weight loss program in overweight or obese subjects with type 2 diabetes High blood glucose level , lipid profile disturbances and plasma homocysteine ( Hcy ) are important risk factors for cardiovascular diseases in patients with type 2 diabetes . This study was conducted to evaluate and compare effects of glimepiride/metformin combination versus gliclazide/metformin combination on cardiovascular risk factors in type-2 diabetes mellitus ( T2DM ) patients . One hundred and eighty T2DM patients were r and omly allocated for treatment with placebo ( control ) , metformin ( 500 mg twice daily ) , glimepiride ( 3 mg once daily ) , gliclazide ( 80 mg once daily ) , metformin plus glimepiride or metformin plus gliclazide for 3 months . We evaluated plasma levels of glucose ( PG ) , glycated hemoglobin ( HbA1C ) , Hcy , vitamin B12 , folic acid and lipid profile before treatment and 3 months post treatment . Compared to metformin treated patients , glimepiride plus metformin induced significant reductions in : fasting plasma glucose , postpr and ial PG level , HbA1C % and Hcy level . Conversely , plasma folic acid and vitamin B12 were significantly increased . The levels of total cholesterol and triglyceride were significantly decreased ; low-density lipoprotein was markedly decreased , whereas high-density lipoprotein was significantly increased and hence risk ratio was signiﬁcantly decreased . Similar results but with lower values were obtained using combination of metformin plus gliclazide on glycemic control only . Combination of glimepiride with metformin was superior to gliclazide plus metformin in alleviating the cardiovascular risk factors in type 2 diabetes mellitus patients Type 2 diabetes mellitus is more prevalent among persons and population s in which obesity or a family history of the disease is present .  Modification of dietary habits and subsequent weight loss ( important steps in the management of both obesity and diabetes ) improve glycemic control . However , glycemic goals are usually not achieved by dietary restriction alone , and pharmacologic intervention is often necessary . Until 1995 , sulfonylurea compounds were the only oral antihyperglycemic agents available in the United States for initial drug therapy for type 2 diabetes ( 1 - 3 ) . These agents have a high rate of secondary failure ( 1 - 3 ) , however , and the addition of other oral agents or insulin is often necessary . Because many persons with type 2 diabetes are overweight and insulin resistant , high doses of insulin are often required to achieve adequate glycemic control . However , insulin therapy is associated with weight gain , which could somewhat vitiate the expected improvement in glycemic control . It is now common to combine therapeutic agents that have complementary mechanisms of action , such as sulfonylurea compounds and insulin ( 1 - 5 ) . With the development of new oral medications-such as biguanides , -glucosidase inhibitors , and thiazolidinediones-that have different modes of action design ed to improve diabetes control , combination therapy has become even more common ( 1 - 6 ) . Metformin , a biguanide , has been approved in the United States for use alone or in combination with sulfonylurea compounds since 1995.Its main mechanisms of action are to decrease hepatic glucose output ( 3 , 7 - 12 ) and improve peripheral insulin sensitivity ( 1 - 3 , 7 , 8) . The use of metformin alone or in combination with sulfonylurea compounds has been shown to improve glycemic control in patients with type 2diabetes ( 1 , 2 , 10 , 12 ) . Blood lipid abnormalities , particularly hypertriglyceridemia , have also improved with metformin use ( 1 - 3 , 7 , 10 , 12 - 14 ) , and weight loss has been reported in many persons ( 1 - 3 , 7 , 10 , 15 , 16).Some physicians recommend metformin as the first drug of choice in the treatment of obese patients with type 2 diabetes ( 9 , 17 ) ; this recommendation has been supported by the recent findings of the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) ( 16 , 18 ) . Metformin-insulin therapy has been used successfully in Europe ( 13 ) , but few reports of this potentially useful combination have been published . The probable clinical importance of the combination of metformin and insulin includes improvements in glycemic control and insulin sensitivity and avoidance of the weight gain that often accompanies improved glycemic control . We evaluated the effect of metformin on glycemic control and exogenous insulin requirements when given in combination with insulin to patients with type 2 diabetes that was poorly controlled by insulin alone . Methods Patients Study patients were required to meet the following criteria : type 2 diabetes diagnosed after 30 years of age and treated for at least 2 years with at least 50 units of insulin per day , age at enrollment younger than 70 years , and a hemoglobin A1c level 8.0 % . We excluded pregnant women ; women trying to become pregnant ; patients with a serum creatinine concentration greater than 132.6 mmol/L ( 1.5mg/dL ) or hepatic enzyme levels greater than twice the upper limit of normal ; and patients with medical conditions that could promote lactic acidosis , such as renal or hepatic disease , congestive heart failure , or chronic obstructive pulmonary disease . All patients provided written informed consent before study entrance . The institutional review board of the University of Texas Southwestern Medical Center at Dallas approved the study protocol . Follow-up Patients who met the inclusion criteria were r and omly assigned in a double-blind fashion to receive metformin or placebo in addition to their current insulin therapy .  Glycemic control , insulin dose requirements , study drug tolerance , body weight , and blood pressure changes were assessed at weeks 2 , 4 , 8 , 12 , 16 , and 24 . Evaluation of Other Study End Points Body weight and blood pressure were measured at every office visit . Patients were weighed while wearing street clothes , and blood pressure was measured when the patient was in a sitting position . Complete medical histories , physical examinations , fasting lipid and lipoprotein profiles , C-peptide concentrations , and serum chemistries were determined at the beginning and end of the study . Intervention Metformin was administered as 500-mg tablets . Metformin and placebo tablets had a similar appearance , thereby preventing identification of the tablets by the investigators or the patients . During the first 2 weeks of the study , patients were instructed to ingest one tablet of the study drug with breakfast and one tablet with supper in addition to their current insulin therapy . At week 2 , the dosage of the study drug was increased to 1500 mg/d(one tablet three times daily with meals ) . At week 4 , the dosage of the study drug was increased to 2000 mg/d , and the insulin dose was adjusted accordingly . At week 8 , the dosage was increased to the maximum dose of 2500 mg/d ( five tablets per day ) . Compliance was assessed by pill count , which was performed at each office visit . During the titration phase , drug tolerance was assessed at every visit . Hypoglycemic episodes and such symptoms as nausea , vomiting , abdominal pain , bloating , flatulence , diarrhea , and anorexia were also assessed at each visit . The dose of the study drug was adjusted when necessary to prevent adverse effects . The patients continued to receive the maximum tolerated dosage from weeks 8 to 24 . Assessment of Glycemic Control and Insulin Dose Adjustments The goal of therapy was to achieve normoglycemia in the absence of serious hypoglycemia . The patients were asked to perform  blood glucose monitoring  at least twice per day ( before breakfast and before supper ) and as necessary ( that is , when symptoms of hypoglycemia occurred ) . Postpr and ial blood glucose monitoring was not done . Daily self-monitoring records and fasting plasma glucose concentrations were review ed at every visit . A patient-directed insulin dose algorithm was not used . At every visit , the insulin dose was adjusted in amount or frequency depending on the patient 's monitoring results , meal schedule , daily schedule , and reported symptoms of hypoglycemia . The insulin dose was decreased if the fasting plasma glucose concentrations were consistently 5.55 mmol/L ( 100 mg/dL ) or if the patient reported symptomatic or asymptomatic hypoglycemia ( blood glucose concentrations 2.78 mmol/L [ 50 mg/dL ] ) . All changes in insulin dose were made by study personnel . Hemoglobin A1c levels were measured by using high-pressure liquid chromatography at baseline and at weeks 8 , 16 , and 24 . Levels within the range of persons without diabetes ( 5.6 % ) were the goal for both groups . Diet Dietary counseling was offered to every patient at screening and at subsequent visits as needed . General guidelines regarding portion sizes from all food groups were given without calculated caloric plans . Changes in daily caloric intake were assessed through review of a 3-day food record at baseline and at the end of the study . Patients were encouraged to maintain baseline levels of physical activity throughout the study . Analytical Determinations Plasma glucose concentrations were determined by using an automated glucose oxidase method ( Glucose Analyser 2 , Beckman Instruments , Fullerton , California ) . C-peptide concentrations were measured by radioimmunoassay using polyclonal antisera . Fasting lipid and lipoprotein concentrations were assessed by using st and ard laboratory methods . Statistical Analysis The efficacy analysis included all patients who met inclusion criteria and had a baseline hemoglobin A1c measurement and at least one postbaseline hemoglobin A1c measurement . Baseline characteristics and incidences of various events between groups were examined by using contingency-table analysis and Wilcoxon rank-sum tests . Paired t-tests with 95 % CIs were used to compare baseline and posttreatment body weight , fasting plasma glucose concentrations , hemoglobin A1c concentrations , daily insulin dose , fasting C-peptide level , fasting lipid profile , and daily caloric intake within and between groups . The Fisher exact test was used to compare the incidence of side effects between groups . A P value less than 0.05 was considered statistically significant . All analyses were conducted by using SPSS software , version 9.0 ( SPSS , Inc. , Chicago , Illinois ) . All results are reported as the mean SD . Skewed data are shown as the mean SD ( median [ minimum , maximum ] ) . Role of the Funding Source Funding for this study was provided in part by a grant from Bristol-Myers Squibb . The study protocol was developed and implemented by the authors . Other than a preliminary statistical evaluation , the analysis and reporting were done by the authors independently of Bristol-Myers Squibb . Dr. Raskin is a member of the Bristol-Myers Squibb speaker 's bureau . Results Baseline Patient Characteristics Fifty-four patients gave informed consent and were r and omly assigned to receive placebo or metformin .  Forty-three patients ( 21 assigned to receive metformin and 22 assigned to receive placebo ) met the entrance criteria and were followed for the entire 24 weeks . Baseline characteristics of the study patients are presented in Tables 1 and 2 . Both groups were comparable in age , body weight , sex , ethnicity , duration of diabetes , duration of insulin therapy , daily insulin dose , mean hemoglobin A1c levels , and all of the analyzed study variables . Table 1 . Baseline Characteristics of Study Patients Table 2 . Comparison of Changes from Baseline Eleven patients did not complete the study . Eight patients were screened but did not return for follow-up and were therefore not r and omly assigned to a treatment group . One patient developed acute congestive heart failure before r and omization and AIMS To compare the impact of three patient counselling strategies for lifestyle changes and to assess the safety and efficacy of ezetimibe on top of statin therapy in hypercholesterolemic high risk patients . METHODS Open , cluster r and omized 3-parallel group trial . Physicians were r and omized between patient motivation on : diet or physical exercise or both . Counselling was adapted to the patient 's baseline Prochaska stage of change . High cardiovascular risk patients , with LDL-C above or equal to 3 mmol/L despite statin therapy for at least 3 months , were enrolled .  Ezetimibe ( 10mg/day ) and patient counselling were started at the same time . Target goal was defined as total cholesterol less than 5 mmol/L and LDL-C above 3 mmol/L. RESULTS Overall 428 physicians enrolled 1,496 patients . At baseline , LDL-C was 3.9+/-0.9 mmol/L and total cholesterol was 6.1+/-1.1 mmol/L. LDL-C decreased by -30.4+/-19.3 % and 869 ( 62 % ) patients achieved target goal . No difference was shown between r and omisation groups . However , improvements in diet consumption patterns were more easily obtained than improvement in physical activity stage of change in non-active patient at baseline . CONCLUSIONS The marked short-term impact ( -30 % ) on LDL-C , although similar between the three groups , slightly exceeds usual LDL-C reductions achieved by this dose of ezetimibe . Decreasing fat consumption seems easier than increasing physical activity . This study confirms the good efficacy , short-term tolerability and safety of ezetimibe on top of statins
Conclusions Compared with high-dose statin therapy , ezetimibe with low-dose statin for more than 3 months may have a beneficial tendency of effects on glycemic control
Purpose Given the increased risk of incident diabetes and the side effects on glycemic control with statin treatment , statin and ezetimibe combination therapy has been widely used .
However , whether the same concern exists in ezetimibe remains uncertain .
This meta- analysis aim ed to investigate the influence of ezetimibe treatment on glycemic control .