Risk of new-onset heart failure in patients using sitagliptin: a population-based cohort study.

AIMS: To examine whether patients using sitagliptin at the time of an acute coronary syndrome event are at increased risk of incident heart failure compared with those not exposed. METHODS: Using US claims data, people with diabetes without a history of heart failure in the 3 years before hospitalization for acute coronary syndrome were identified for the period 2004 to 2010. We used a nested case-control design, whereby cases were patients who developed incident heart failure <30 days after admission to hospital for acute coronary syndrome and were matched by age and sex with up to 10 controls with no heart failure. Subjects exposed or not exposed to sitagliptin in the 90 days before acute coronary syndrome admission were compared using conditional logistic regression after adjustment for clinical and laboratory data, healthcare utilization and propensity scores. RESULTS: In total, 457 cases of heart failure developing de novo after diagnosis of acute coronary syndrome were matched to 4570 controls. The average age of the subjects was 55 years and 65% were male. Overall, 11 of 147 (7%) people exposed to sitagliptin developed heart failure compared with 446 of the 4880 people not exposed (9%, adjusted odds ratio 0.75, 95% CI 0.38-1.46; P=0.40). Sitagliptin exposure before acute coronary syndrome was not associated with an increased risk of death or heart failure combined (7% vs 9%, adjusted odds ratio 0.66, 95% CI 0.34-1.28). CONCLUSIONS: In our sample of patients who are at high risk of heart failure after acute coronary syndrome, sitagliptin exposure was not associated with an increased risk of de novo heart failure.

Comparison of basal insulin therapies with regard to the risk of acute myocardial infarction in patients with type 2 diabetes: an observational cohort study.

AIMS: To assess the risk of acute myocardial infarction (AMI) in patients with type 2 diabetes mellitus treated with long-acting insulin analogues in comparison with other basal insulin therapy. METHODS: We used German insurance claims data from the years 2004-2009 to conduct a study in a retrospective cohort of patients with type 2 diabetes. Naïve insulin users were defined as patients who had an insulin-free history before the first prescription of long-acting analogue insulin, human NPH insulin or premixed insulin and who were pretreated with oral antidiabetic drugs. Adjusted hazard ratios (HRs) of AMI and corresponding 95% confidence intervals (CIs) were calculated using sex-stratified Cox models. Propensity-score-matched analyses were conducted as sensitivity analyses. RESULTS: We identified 21,501 new insulin users. Patients treated with premixed insulin were older than patients treated with analogue or NPH insulin (mean age 70.7 vs. 64.1 and 61.6 years, respectively) and had more comorbidities. Regarding the risk of AMI, adjusted HRs showed no statistically significant difference between NPH and analogue insulin (HR 0.94, 95% CI 0.74-1.19), but a higher risk for premixed than for analogue insulin (HR 1.27, 95% CI 1.02-1.58). Contrary to the primary analysis, the propensity-score-matched analysis did not show an increased risk for premixed insulin. CONCLUSIONS: In contrast to a former database study, no difference was observed for the risk of AMI between long-acting analogue and NPH insulin in this study. Neither long-acting analogue insulin nor premixed insulin appears to be associated with AMI in patients with type 2 diabetes.

Comparative cardiovascular safety of insulin secretagogues following hospitalization for ischemic heart disease among type 2 diabetes patients: a cohort study.

AIM: To evaluate the association between insulin secretagogues and adverse cardiovascular sequelae in type 2 diabetes patients hospitalized for ischemic heart disease (IHD). METHODS: Administrative health records from Alberta, Canada between 1998 and 2010 were used to identify 2,254 gliclazide, 3,289 glyburide and 740 repaglinide users prior to an IHD-related hospitalization. Multivariable Cox regression models were used to compare the 30-day risk of a composite outcome of all-cause mortality or new onset of atrial fibrillation, stroke, heart failure or myocardial infarction according to insulin secretagogue use. RESULTS: Mean (SD) age was 76.1 (6.9) years, and 60.7% were men. The composite outcome occurred in 322 (30.2%) gliclazide users, 455 (28.1%) glyburide users and 81 (23.4%) repaglinide users within 30 days of IHD hospitalization. There were no differences in risk for glyburide use (adjusted hazard ratio [aHR] 0.91; 95% confidence interval [CI] 0.78-1.05) or repaglinide use (aHR 0.80; 95% CI 0.63-1.03) compared to gliclazide. Similar results were observed in analyses for each element of the composite outcome. CONCLUSIONS: In older patients with type 2 diabetes hospitalized for IHD, prior use of gliclazide, glyburide, or repaglinide appears to be associated with a similar risk of adverse cardiovascular sequelae.

Development of heart failure in Medicaid patients with type 2 diabetes treated with pioglitazone, rosiglitazone, or metformin.

BACKGROUND: Medicaid covers a high-risk population typically underrepresented in clinical trial data and largely absent in observational studies of real-world cardiovascular risks associated with thiazolidinediones (TZDs), such as pioglitazone and rosiglitazone, which are used to manage type 2 diabetes. In November 2013, the FDA removed prescribing restrictions for rosiglitazone in light of new evidence that rosiglitazone did not increase the risk of heart attack compared with standard type 2 diabetes medications. Further investigation is needed to elucidate whether the risk of heart failure (HF) associated with TZDs may be exacerbated in the Medicaid population. OBJECTIVE: To determine the relative risk of incident HF in patients initiating rosiglitazone, pioglitazone, and metformin therapy in a Medicaid population. METHODS: We retrospectively examined claims data for patients with type 2 diabetes enrolled in Maryland State Medicaid and managed care or fee-for-service programs between July 2005 and June 2010. Patients initiated on metformin, pioglitazone, or rosiglitazone treatments were extracted for analysis. Relative risks of incident HF after initiating treatment were compared using survival analysis, adjusting for switching or adding antidiabetic therapies during follow-up and other baseline risk factors for HF. RESULTS: Of 6,271 patients meeting inclusion criteria, 88% were started on metformin; 7% were started on pioglitazone; and 5% were started on rosiglitazone. Patients who initiated rosiglitazone had higher risk of HF than patients who initiated metformin using either univariate (HR = 1.81, 95% CI = 1.37-2.39), multivariate (HR = 1.57, 95% CI = 1.15-2.15), or propensity score-matched (HR = 1.79, 95% CI = 1.16-2.76) analysis. There was no significant difference in risk between patients who initiated pioglitazone and metformin therapy. CONCLUSIONS: Compared with metformin, there may be higher risk of developing HF in Medicaid patients started on rosiglitazone but not pioglitazone. While pioglitazone was associated with a lower risk of developing HF compared with rosiglitazone, health care professionals should continue to work closely with their patients to determine the treatment options most appropriate.

Assessment of left ventricular myocardial systolic acceleration in diabetic rats using velocity vector imaging.

OBJECTIVES: The purpose of this study was to investigate how the myocardial acceleration during isovolumic contraction changed in rats with diabetic cardiomyopathy and a normal left ventricular ejection fraction (LVEF) by using velocity vector imaging. METHODS: Velocity vector imaging was performed in 12 control rats and 15 rats with streptozotocin-induced diabetic cardiomyopathy 12 weeks after streptozotocin injection. The segmental radial displacement, velocity, acceleration, and percent wall thickening were measured at the mid-left ventricular (LV) level. RESULTS: Compared to control rats, rats with cardiomyopathy had a significant decrease in the peak radial acceleration during isovolumic contraction in most segments of the LV wall (including the anterior, anterolateral, inferolateral, and inferior segments; P < .05) but a similar LVEF, fractional shortening, and segmental displacement. Rats with cardiomyopathy also had a significant increase in LV end-diastolic and end-systolic diameters when corrected for body mass (P < .001; P = .003, respectively) and a significant decrease in the radial peak systolic velocities of the inferolateral and inferior wall segments (P < .05). In addition, rats with cardiomyopathy had a significant decrease in the peak radial diastolic acceleration in most segments of the LV wall (except for the anterolateral one; P< .05) but similar peak radial diastolic velocities in all LV wall segments compared to controls. Pathologic examination in rats with cardiomyopathy revealed ultrastructural impairment of the capillary and cardiocyte without any atherosclerotic lesion in the coronary artery compared to control rats. CONCLUSIONS: Myocardial acceleration during isovolumic contraction decreases in rats with diabetic cardiomyopathy and a preserved LVEF, suggesting the presence of regional LV systolic dysfunction.

Assessment of cardiac inflammation and remodeling during the development of streptozotocin-induced diabetic cardiomyopathy in vivo: a time course analysis.

In this study, we examined cardiac inflammation, fibrosis and left ventricular (LV) function during the development of streptozotocin (STZ)-induced diabetic cardiomyopathy using an animal model of diabetes mellitus (DM). Diabetes was induced in 22 Sprague­Dawley rats by an intraperitoneal single injection of STZ (70 mg/kg). Non-diabetic animals served as the controls (n=6). LV function was documented using the conductance catheter technique 2 and 6 weeks after the induction of diabetes. Cardiac tissue was analyzed for cardiac immune cell infiltration, oxidative stress and remodeling in rats with STZ-induced diabetes at 2 different time points by immunohistochemistry. Cardiac function was significantly impaired in the diabetic animals. After 2 weeks, the induction of diabetes resulted in impaired cardiac function indexed by a decrease in systolic and diastolic LV function. This impairment of LV performance continued for up to 6 weeks after the STZ injection. This was associated with an increase in cardiac CD3+ and CD8a+ immune cell invasion and fibrosis, indexed by an increase in collagen content (p<0.05). Furthermore, oxidative stress response and matrix remodeling were increased after 2 weeks and this continued for up to 6 weeks after the induction of diabetes. In conclusion, cardiac dysfunction is associated with cardiac inflammation and adverse remodeling in experimental diabetic cardiomyopathy. Our results suggest that the model of STZ-induced diabetic cardiomyopathy is a robust model for investigating cardiac immune response and LV remodeling processes under diabetic conditions.