Sitagliptin does not reduce the risk of cardiovascular death or hospitalization for heart failure following myocardial infarction in patients with diabetes : observations from TECOS

Background To examine the effects of the DPP-4i sitagliptin on CV outcomes during and after incident MI in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Methods TECOS randomized 14,671 participants with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) to sitagliptin or placebo, in addition to usual care. For those who had a within-trial MI, we analyzed case fatality, and for those with a nonfatal MI, we examined a composite cardiovascular (CV) outcome (CV death or hospitalization for heart failure [hHF]) by treatment group, using Cox proportional hazards models left-censored at the time of the first within-trial MI, without and with adjustment for potential confounders, in intention-to-treat analyses. Results During TECOS, 616 participants had >= 1 MI (sitagliptin group 300, placebo group 316, HR 0.95, 95% CI 0.81-1.11, P = 0.49), of which 25 were fatal [11 and 14, respectively]). Of the 591 patients with a nonfatal MI, 87 (15%) died subsequently, with 66 (11%) being CV deaths, and 57 (10%) experiencing hHF. The composite outcome occurred in 58 (20.1%; 13.9 per 100 person-years) sitagliptin group participants and 50 (16.6%; 11.7 per 100 person-years) placebo group participants (HR 1.21, 95% CI 0.83-1.77, P = 0.32, adjusted HR 1.23, 95% CI 0.83-1.82, P = 0.31). On-treatment sensitivity analyses also showed no significant between-group differences in post-MI outcomes. Conclusions In patients with type 2 diabetes and ASCVD experiencing an MI, sitagliptin did not reduce subsequent risk of CV death or hHF, contrary to expectations derived from preclinical animal models. Trial registration clinicaltrials.gov no. NCT00790205Peer reviewe

Longitudinal medical resources and costs among type 2 diabetes patients participating in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS)

Aims: TECOS, a cardiovascular safety trial (ClinicalTrials.gov identifier: NCT00790205) involving 14 671 patients with type 2 diabetes and cardiovascular disease, demonstrated that sitagliptin was non-inferior to placebo for the primary composite cardiovascular outcome when added to best usual care. This study tested hypotheses that medical resource use and costs differed between these 2 treatment strategies. Materials and methods: Information concerning medical resource use was collected on case report forms throughout the trial and was valued using US costs for: Medicare payments for hospitalizations, medical procedures and outpatient visits, and wholesale acquisition costs (WAC) for diabetes-related medications. Hierarchical generalized linear models were used to compare resource use and US costs, accounting for variable intercountry practice patterns. Sensitivity analyses included resource valuation using English costs for a UK perspective. Results: There were no significant differences in hospitalizations, inpatient days, medical procedures, or outpatient visits during follow-up (mean and median 3.0 years in both groups). Hospitalization rates appeared to diverge after 2 years, with lower rates among sitagliptin-treated vs placebo patients after 2.5 years (relative rate, 0.90 [95% CI, 0.83-0.97]; P =.01). Mean medical costs, exclusive of study medication, were 11 937 USD in the sitagliptin arm and 12 409 USD in the placebo arm (P =.06). Mean sitagliptin costs based on undiscounted WAC were 9978 USD per patient. Differential UK total costs including study drug costs were smaller (911 GBP), primarily because of lower mean costs for sitagliptin (1072 GBP). Conclusions: Lower hospitalization rates across time with sitagliptin slightly offset sitagliptin treatment costs over 3 years in type 2 diabetes patients at high risk for cardiovascular events

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Randomized controlled pilot trial of a hand-held patient-oriented, insulin regimen optimizer

A robust, hand-held, patient-oriented insulin regimen optimizer (POIRO) has been developed. Relevant information is entered by selecting appropriate items from choices displayed on a touch-sensitive screen rather than a conventional keyboard. All data items are recorded, together with their time and date of entry, and may be recalled at any time with glucose values displayed graphically to provide an overview of glycaemic control. When requested, an integral, hybrid, statistical and rule-based expert system program uses all available data to suggest an optimum insulin dose within physician determined, pre-set limits. POIRO has been formally evaluated in a randomized crossover pilot trial, comparing two 3 week periods with and without decision support, in six patients with type 1 diabetes. Mean (SE) pre-prandial blood glucose levels were significantly lower during the period when decision support was available (7·5 (0·4) versus 8·9 (0·4) mmol/1, p = 0·015) with no increase in the frequency or severity of hypoglycaemia. The device, which was well received by the patients, may offer a relatively inexpensive method of providing expert diabetic advice at a distance. The persistence of improved glycaemic control, even after decision support was switched off, suggests the device could be used intermittently by patients and may have educational value. © 1996 Informa UK Ltd All rights reserved

Recull factici de fragments de llibres litúrgics

Localització: Barcelona, Biblioteca de Catalunya, UAB Ms. 34.PergamíNotació musical amb tetragrames (UAB Ms. 34/2, 4-5, 8, 12, 15-16); excepte en el UAB Ms. 34/1 que no hi ha línies.En alguns documents, hiha anotacions manuscrites amb la transcripció dels textos (UAB Ms. 34/3, 12, 14, 18)Data aprox. deduïda del contingut i característiques dels textos.Els UAB Ms. 34/18-30 són una munió de petits fragments muntats sobre 13 fulls de plàstic; juntament amb els 34/22 i 34/30, muntats sobre f. de plàstic, hi ha a cada un 2 petits fragments sense muntar.Rúbriques en vermell. Caplletres alternant el vermell i blau, algunes amb filigranes.Fragments de diferents llibres litúrgics, alguns d'ells identificats, que corresponen a textos bíblics, patrístics, sobre màrtirs, misses, oficis de Pasqua, festes de sants i himnes

Safety of sitagliptin in patients with type 2 diabetes and chronic kidney disease: Outcomes from TECOS.

<h4>Aims</h4> <p>To characterize the incidence of diabetes-associated complications and assess the safety of sitagliptin in participants with chronic kidney disease (CKD) in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS).</p> <h4>Materials and Methods</h4> <p>For participants with baseline eGFR measurements (n=14,528), baseline characteristics and safety outcomes were compared for the CKD cohort (eGFR <60 mL/min per 1.73 m2) versus those without CKD. Within the CKD cohort, the same analyses were performed comparing sitagliptin- and placebo-assigned participants. Baseline characteristics were summarized for all participants, and serious adverse events were analyzed in those who received at least one dose of study medication. Adverse events of interest and diabetes complications were summarized for the intention-to-treat population.</p> <h4>Results</h4> <p>CKD was present in 3324 (23%) participants at entry into TECOS. The mean (SD) age for this CKD cohort was 68.8 (7.9) years, mean diabetes duration was 13.7 (9.0) years, and 62% were men. Incidences of serious adverse events, malignancy, bone fracture, severe hypoglycemia and most categories of diabetes complications were higher in the CKD cohort compared with those without CKD. Over ~2.8 median years’ follow-up, CKD participants assigned to sitagliptin had similar rates of diabetic eye disease, diabetic neuropathy, renal failure, malignancy, bone fracture, pancreatitis and severe hypoglycemia as placebo-assigned participants.</p> <h4>Conclusions</h4> <p>Participants in TECOS with CKD had higher incidences of serious adverse events and diabetes complications than those without CKD. Treatment with sitagliptin was generally well tolerated with no meaningful differences observed in safety outcomes between those with CKD assigned sitagliptin or placebo.</p

Safety of sitagliptin in patients with type 2 diabetes and chronic kidney disease: Outcomes from TECOS.

Aims To characterize the incidence of diabetes-associated complications and assess the safety of sitagliptin in participants with chronic kidney disease (CKD) in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Materials and Methods For participants with baseline eGFR measurements (n=14,528), baseline characteristics and safety outcomes were compared for the CKD cohort (eGFR &lt;60 mL/min per 1.73 m2) versus those without CKD. Within the CKD cohort, the same analyses were performed comparing sitagliptin- and placebo-assigned participants. Baseline characteristics were summarized for all participants, and serious adverse events were analyzed in those who received at least one dose of study medication. Adverse events of interest and diabetes complications were summarized for the intention-to-treat population. Results CKD was present in 3324 (23%) participants at entry into TECOS. The mean (SD) age for this CKD cohort was 68.8 (7.9) years, mean diabetes duration was 13.7 (9.0) years, and 62% were men. Incidences of serious adverse events, malignancy, bone fracture, severe hypoglycemia and most categories of diabetes complications were higher in the CKD cohort compared with those without CKD. Over ~2.8 median years’ follow-up, CKD participants assigned to sitagliptin had similar rates of diabetic eye disease, diabetic neuropathy, renal failure, malignancy, bone fracture, pancreatitis and severe hypoglycemia as placebo-assigned participants. Conclusions Participants in TECOS with CKD had higher incidences of serious adverse events and diabetes complications than those without CKD. Treatment with sitagliptin was generally well tolerated with no meaningful differences observed in safety outcomes between those with CKD assigned sitagliptin or placebo.</p