New use of rosiglitazone decreased following publication of a meta-analysis suggesting harm. Effects of rosiglitazone on plasma brain natriuretic peptide levels and myocardial performance index in patients with type 2 diabetes mellitus. Beneficial effects of rosiglitazone on novel cardiovascular risk factors in patients with Type 2 diabetes mellitus. Rosiglitazone preserves islet beta-cell function of adult-onset latent autoimmune diabetes in 3 years follow-up study. A prospective randomized trial comparing the clinical and endocrinological outcome with rosiglitazone versus laparoscopic ovarian drilling in patients with polycystic ovarian disease resistant to ovulation induction with clomiphene citrate. Rosiglitazone produces a greater reduction in circulating platelet activity compared with gliclazide in patients with type 2 diabetes mellitus--an effect probably mediated by direct platelet PPARgamma activation. Rosiglitazone treatment increases subcutaneous adipose tissue glucose uptake in parallel with perfusion in patients with type 2 diabetes: a double-blind, randomized study with metformin. Effect of rosiglitazone versus insulin on the pancreatic beta-cell function of subjects with type 2 diabetes. Once- and twice-daily dosing with rosiglitazone improves glycemic control in patients with type 2 diabetes.
It is uncertain whether meta-analyses lead to changes in prescribing practices. We studied trends in the prescribing of glucose-lowering therapy before and after the publication of a meta-analysis suggesting harm from rosiglitazone.
                We examined the prescription records of all residents of Ontario, Canada, aged > or = 66 years. For each week between January and December 2007, we identified new users of five categories of glucose-lowering medications: rosiglitazone, pioglitazone, metformin, glibenclamide (glyburide) and insulin. The effect of the meta-analysis was assessed using interventional autoregressive integrated moving-average models.
                Following the release of the meta-analysis, there was a sudden decline in new users of rosiglitazone (P = 0.01), mirrored by a nearly identical but transient increase in new users of pioglitazone (P < 0.001). There was also a net decline in new users of thiazolidinediones as a class (P < 0.001). The number of new users of other glucose-lowering medications did not change.
                A highly-publicized meta-analysis regarding rosiglitazone's potential harms led to an abrupt decline in new users of the drug, as well as a transient surge in new use of pioglitazone. Thiazolidinediones (TZD) have become a powerful tool for lowering insulin resistance. The problem of cardiovascular adverse events including fluid retention and risk of heart failure should be well known and recognised. We aimed to evaluate the long-term effects of rosiglitazone on cardiac function and fluid dynamics. Forty-six type 2 diabetic patients were randomised to treatment with rosiglitazone or metformin or to a control group. There are no significant differences between the groups in the duration of diabetes, HbA1c, plasma brain natriuretic peptide (BNP) levels, body mass index and myocardial performance indexes (MPIs) before the treatment. After three and six months all these parameters were repeated. Rosiglitazone increased plasma BNP levels and worsened MPIs 3 months after the start of treatment. Also left ventricular end-systolic volume increased and weight gain was observed. But these results were statistically non-significant (all p>0.05). When we continued rosiglitazone treatment to six months the increase in BNP levels became soft and statistically significant improvements were seen in MPIs (p<0.01). Also left ventricular end-systolic volume decreased significantly (p=0.004) and weight gain was stopped. In patients with type 2 diabetes, TZD treatment might have slight adverse effects on ventricular contractility and fluid dynamics at the beginning of the therapy. However, these changes seem to stabilise in the long term. Impaired exercise capacity, adiponectin, MMPs and TIMPs have all been implicated in the development of cardiovascular disease. The aim of our study was to determine the effects of rosiglitazone on these factors in diabetic patients.
                Seventy individuals with Type 2 diabetes were assigned randomly to either a rosiglitazone group (8 mg/day, RG) or a control group (CG) for 6 months. All participants took gliclazide 160 mg plus metformin 1700 mg in stable dose. None of the individuals had diabetic complications or had previously participated in an exercise programme. Anthropometric parameters, VO2 peak, oxygen pulse, glycaemic indices, lipid profile, adiponectin, insulin resistance, blood pressure and serum MMP-9, TIMP-1, TIMP-2 levels were assessed at baseline and at the end of the study. After Bonferroni adjustment, a P-value < 0.017 was assumed to be statistically significant.
                Rosiglitazone treatment significantly increased VO2 peak (P < 0.0001), the duration of the exercise test (P < 0.0001), oxygen pulse (P = 0.010) and TIMP-2 levels (P = 0.008) in comparison with CG. Insulin resistance, hyperglycaemia, diastolic blood pressure and MMP-9 levels were also reduced (P < 0.017). Fat mass, lipid profile, TIMP-1 levels and MMP9 : TIMP-1 ratio were unaltered after rosiglitazone treatment. There were no significant changes in these parameters in control subjects. In univariate analysis, the rosiglitazone-induced increment of VO2 peak was associated with alterations in plasma adiponectin (r = 0.691), HOMA-IR (r = -0.782) and HbA(1c) (r = -0.676) (P < 0.017). These relationships retained significance after multiple regression analysis (P = 0.005).
                Rosiglitazone treatment increases cardiorespiratory fitness and modulates favourably serum adiponectin, MMP-9 and TIMP-2 levels. Whether these effects produce cardiovascular benefits in the long term requires further investigation. The newly developed insulin sensitizer-thiazolidinediones have the potential to downregulate inflammation and autoimmune response. The objective of this study was to observe the beneficial effects on beta-cell function in the LADA patients treated with rosiglitazone. 54 LADA patients were assigned to oral hypoglycemic agents group (GAD-Ab<175 U/mL and FCP>0.3 nmol/L) or early insulin administration group (GAD-Ab>or=175 U/mL or GAD-Ab<175 U/mL and FCP<or=0.3 nmol/L). Then, those patients were randomly assigned to receive sulfonylureas (SUs group) or rosiglitazone (RSG group) therapy, or to receive insulin alone (INS group) or rosiglitazone plus insulin (INS+RSG group). Plasma glucose, HbA1c, fasting C-peptide (FCP) and C-peptide after 2h 75-g glucose load (PCP) were determined every 6 months. The levels of PCP and delta CP were higher in RSG group compared with those in SUs group after the 18th month. The PCP level (after the 12th month) and delta CP level (after the 18th month) in INS+/-RSG group were higher than those in INS group. Rosiglitazone combined with insulin wherever or not preserved beta-cell function in LADA patients after 3 years. Rosiglitazone, an insulin sensitizing agent is used currently in women with clomiphene citrate (CC) resistant polycystic ovarian syndrome (PCOS). Our study proposed to compare the efficacy of rosiglitazone and CC with laparoscopic ovarian drilling (LOD) and CC in terms of biochemical effects, ovulation rate and pregnancy rate in patients of PCOS resistant to CC.
                This prospective randomised trial included 43 patients of PCOS resistant to CC. Twenty-two women were assigned to the rosiglitazone (4 mg twice daily) and CC group and other 21 patients underwent unilateral LOD and then received CC and multivitamins. The treatment continued for six cycles in both the groups. The biochemical response, ovulation rate and pregnancy rate over a follow up period of 6 months were compared.
                Treatment with rosiglitazone and CC or LOD and CC resulted in increased ovulation (80.8 vs. 81.5%) and pregnancy (50 vs. 42.8%), respectively. There was no statistical difference between the two groups in terms of biochemical response, ovulation rate and pregnancy rate.
                To avoid the risk of adverse effects of LOD preference may be given to the use of rosiglitazone and CC therapy in patients of PCOS resistant to CC. Type 2 diabetes mellitus (T2DM) is associated with enhanced platelet activation. We conducted a randomised double-blind study to compare the effects of combination metformin and rosiglitazone or metformin and gliclazide therapy on platelet function in persons with T2DM.
                Fifty subjects on metformin monotherapy received either rosiglitazone 4 mg or gliclazide 80 mg. HbA1c, HOMA-R, markers of platelet activation, inflammation, endothelial activation and oxidative stress were measured at baseline and after 24 weeks of treatment. Separate in vitro platelet function studies were conducted on platelets pre-incubated with rosiglitazone and gliclazide.
                A significantly greater reduction in platelet aggregation was observed in the rosiglitazone treated group compared to gliclazide. HbA1c and markers of endothelial activation were reduced to a similar extent in both groups. A significant reduction in HOMA-R, markers of inflammation and oxidative stress was only observed with rosiglitazone. Reduction in platelet aggregation with rosiglitazone correlated with reduction in oxidative stress. In the in vitro study, rosiglitazone produced significantly greater reduction in platelet aggregation compared with gliclazide.
                Greater reduction in platelet activity observed with rosiglitazone may be related to reduced oxidative stress and a possible direct PPARgamma mediated effect on platelet function. We have shown that rosiglitazone increases whole-body and adipose tissue insulin sensitivity in humans.
                The aim of this study was to further examine whether possible changes in adipose perfusion could explain increased adipose tissue glucose uptake (GU).
                Thirty-seven patients with newly diagnosed type 2 diabetes were included.
                Patients were randomized into treatment with rosiglitazone, metformin, or placebo for 26 wk in a double-blinded trial.
                Femoral adipose flow and GU were measured with [15O]H2O, [18F]fluorodeoxyglucose and positron emission tomography during euglycemic hyperinsulinemia. Adipose masses were measured using magnetic resonance imaging.
                Metformin and rosiglitazone treatment improved glycemic control, but only rosiglitazone increased whole-body insulin sensitivity. Rosiglitazone treatment increased flow by 72% (P < 0.01) and GU by 23% (P < 0.05) and thereby decreased adipose tissue glucose extraction by 18% (P < 0.05); no changes were observed in the metformin or placebo-treated groups. When the adipose masses were taken into account, rosiglitazone treatment increased flow by 73% (P < 0.01) and GU by 24% (P < 0.05). During hyperinsulinemia, flow correlated with GU (r = 0.63; P < 0.01).
                In conclusion, s.c. GU is associated with flow in patients with type 2 diabetes. Rosiglitazone treatment enhances GU and flow but decreases glucose extraction, suggesting that perfusion may contribute to adipose tissue insulin sensitization by rosiglitazone. In a previous study, we found observational evidence of improvement in beta-cell function when rosiglitazone was added to a failing oral antihyperglycemic regimen consisting of sulfonylureas and metformin. To confirm our previous observations, we designed and performed a prospective, randomized, and controlled study.
                A total of 17 subjects with type 2 diabetes, inadequately controlled on a maximized oral antihyperglycemic double regimen of glimepiride and metformin, were randomized to the addition of rosiglitazone or insulin to their treatment regimens for a period of 6 months. At baseline and at 6 months, the following were performed: measurement of fasting plasma glucose, fasting proinsulin, and insulin levels; frequently sampled intravenous glucose tolerance test; and glucagon stimulation test for C-peptide.
                Nine subjects were randomized to the addition of 8 mg rosiglitazone, and eight subjects were randomized to the addition of one injection of insulin (premixed 70/30) before their evening meal. The treatment groups were well matched for age, duration of diabetes, and BMI. Most important, the HbA(1c) was well matched between groups before treatment (8.7 +/- 0.3 and 9.0 +/- 0.3%; NS) and at the end of the 6 months (7.8 +/- 0.5 and 7.8 +/- 0.3%; NS). After 6 months, at the end of the study, there was a significant improvement in acute insulin response to glucose in the rosiglitazone group (+15.3 microIU x ml(-1) x 10 min(-1); P < 0.001) that led to an increase in the disposition index from 0.18 at baseline to 4.18 at 6 months (P = 0.02). Furthermore, at the end of the study, the proinsulin-to-insulin ratio had decreased in the rosiglitazone group by 36% (P = 0.03) but did not change significantly in the insulin treatment group.
                Rosiglitazone, but not insulin, induced a recovery of pancreatic beta-cell function, as evidenced by the restoration of the first-phase insulin response to glucose, improvement in the disposition index, and a decrease in the proinsulin-to-insulin ratio in subjects with type 2 diabetes in whom oral antihyperglycemic therapy failed. This improvement was independent of the correction of glucotoxicity. To determine the efficacy of rosiglitazone compared with placebo in reducing hyperglycemia.
                After a 4-week placebo run-in period, 959 patients were randomized to placebo or rosiglitazone (total daily dose 4 or 8 mg) for 26 weeks. The primary measure of efficacy was change in the HbA1c concentration.
                Rosiglitazone produced dosage-dependent reductions in HbA1c of 0.8, 0.9, 1.1, and 1.5% in the 4 mg o.d., 2 mg b.i.d., 8 mg o.d., and 4 mg b.i.d. groups, respectively, compared with placebo. Clinically significant decreases from baseline in HbA1c were observed in drug-naive patients at all rosiglitazone doses and in patients previously treated with oral monotherapy at rosiglitazone 8 mg o.d. and 4 mg b.i.d. Clinically significant decreases from baseline in HbA1c were also observed with rosiglitazone 4 mg b.i.d. in patients previously treated with combination oral therapy. Approximately 33% of drug-naive patients treated with rosiglitazone achieved HbA1c < or =7% at study end. The proportions of patients with at least one adverse event were comparable among the rosiglitazone and placebo groups. There was no evidence of hepatotoxicity in any treatment group. There were statistically significant increases in weight and serum lipids in all rosiglitazone treatment groups compared with placebo. For LDL and HDL cholesterol, the observed increase appeared to be dose related.
                Rosiglitazone at total daily doses of 4 and 8 mg significantly improved glycemic control in patients with type 2 diabetes and was well tolerated.
New studies should focus on patient-oriented outcomes to clarify the benefit-risk ratio of rosiglitazone therapy. Safety data and adverse events of all investigations (published and unpublished) should be made available to the public.