sitagliptin-phosphate and Drug-Related-Side-Effects-and-Adverse-Reactions

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).. 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 m. 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 hypoglycaemia and most categories of diabetes complications were higher in the CKD cohort compared with those without CKD. Over ~2.8 median years of follow-up, CKD participants assigned to sitagliptin had rates of diabetic eye disease, diabetic neuropathy, renal failure, malignancy, bone fracture, pancreatitis and severe hypoglycaemia similar to those of placebo-assigned participants.. 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 in safety outcomes observed between those with CKD assigned to sitagliptin or placebo.

Topics: Aged; Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Drug-Related Side Effects and Adverse Reactions; Female; Glomerular Filtration Rate; Humans; Male; Middle Aged; Placebos; Renal Insufficiency, Chronic; Sitagliptin Phosphate; Treatment Outcome

Fractures are significantly associated with increased morbidity and mortality in older individuals; additionally, patients with diabetes mellitus are highly prone to fractures. The aim of the present study was to examine the association between dipeptidyl peptidase-4 (DPP-4) inhibitor use and the risk of fracture in older patients by analyzing data obtained from spontaneous adverse event reporting databases from the United States and Japan.. Data on older patients registered in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) from the first quarter of 2013 to the end of 2019 and data registered in the Japanese Adverse Drug Event Report database (JADER) from April 2004 to December 2019 were used. Reporting odds ratio (ROR) and information component (IC) values were used for disproportionality analysis.. Significant inverse associations between DPP-4 inhibitor use and fracture were found for DPP-4 inhibitors as a whole (ROR = 0.80; 95% CI = 0.73 - 0.88; IC = -0.31, 95% CI = -0.46 to -0.17); linagliptin (ROR = 0.74; 95% CI = 0.59 - 0.94; IC = -0.42, 95% CI = -0.75 to -0.08); and sitagliptin (ROR = 0.77; 95% CI = 0.68 - 0.88; IC = -0.36, 95% CI = -0.55 to -0.17) in the analyses of FAERS data. Similarly, significant inverse associations were also found for DPP-4 inhibitors as whole (ROR = 0.71; 95% CI = 0.59 to 0.86; IC = -0.46, 95% CI = -0.74 to -0.18); sitagliptin (ROR = 0.70; 95% CI = 0.52 - 0.95; IC = -0.49, 95% CI = -0.93 to -0.05); and vildagliptin (ROR = 0.54; 95% CI = 0.35 - 0.83; IC = -0.85, 95% CI = -1.49 to -0.22) in the analyses of JADER data.. Our analysis of adverse event databases using different algorithms revealed that DPP-4 inhibitor use was inversely associated with fracture in older patients.

Topics: Adverse Drug Reaction Reporting Systems; Aged; Databases, Factual; Dipeptidyl-Peptidase IV Inhibitors; Drug-Related Side Effects and Adverse Reactions; Humans; Hypoglycemic Agents; Pharmaceutical Preparations; Sitagliptin Phosphate; United States; United States Food and Drug Administration

Topics: Cough; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug-Related Side Effects and Adverse Reactions; Humans; Nasopharyngitis; Observer Variation; Risk Assessment; Sitagliptin Phosphate

Identifying the potential side effects of drugs is crucial in clinical trials in the pharmaceutical industry. The existing side effect prediction methods mainly focus on the chemical and biological properties of drugs. This study proposes a method that uses diverse information such as drug-drug interactions from DrugBank, drug-drug interactions from network, single nucleotide polymorphisms, and side effect anatomical hierarchy as well as chemical structures, indications, and targets. The proposed method is based on the assumption that properties used in drug repositioning studies could be utilized to predict side effects because the phenotypic expression of a side effect is similar to that of the disease. The prediction results using the proposed method showed a 3.5% improvement in the area under the curve (AUC) over that obtained when only chemical, indication, and target features were used. The random forest model delivered outstanding results for all combinations of feature types. Finally, after identifying candidate side effects of drugs using the proposed method, the following four popular drugs were discussed: (1) dasatinib, (2) sitagliptin, (3) vorinostat, and (4) clonidine.

Topics: Area Under Curve; Clonidine; Dasatinib; Drug Interactions; Drug Repositioning; Drug-Related Side Effects and Adverse Reactions; Humans; Machine Learning; Polymorphism, Single Nucleotide; Sitagliptin Phosphate; Vorinostat

Topics: Diabetes Mellitus, Type 2; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Evidence-Based Medicine; Humans; Metformin; Sitagliptin Phosphate

In Italy, the reimbursed use of incretin mimetics and incretin enhancers was subject to enrollment of patients into a web-based system recording the general demographic and clinical data of patients. We report the utilization data of glucagon-like peptide 1 (GLP1) receptor agonists and dipeptidylpeptidase-4 (DPP4) inhibitors in clinical practice as recorded by the Italian Medicines Agency (AIFA) Monitoring Registry.. From February 2008 to August 2010, 75,283 patients with type 2 diabetes were entered into the registry and treated with exenatide, sitagliptin, or vildagliptin. The treatment was administered to patients in a wide range of ages (≥75 years, n = 6125 cases), body mass index (BMI) (≥35 kg/m(2), n = 22,015), and metabolic control (HbA(1c) ≥ 11% ((96 mmol/mol), n = 3151). Overall, 1116 suspected adverse drug reactions were registered, including 12 cases of acute pancreatitis (six on exenatide). Hypoglycemic episodes mainly occurred in combination with sulfonylureas. Treatment discontinuation for the three drugs (logistic regression analysis) was negatively associated with the male gender and positively with baseline HbA1c, diabetes duration, and, limitedly to DPP-4 inhibitors, with BMI. Treatment discontinuation (including loss to follow-up, accounting for 21-26%) was frequent. Discontinuation for treatment failure occurred in 7.7% of cases (exenatide), 3.8% (sitagliptin), and 4.1% (vildagliptin), respectively, corresponding to 27-40% of all discontinuations, after excluding lost to follow-up. HbA1c decreased on average by 0.9-1.0% (9 mmol/mol). Body weight decreased by 3.5% with exenatide and by 1.0-1.5% with DPP-4 inhibitors.. In the real world of Italian diabetes centers, prescriptions of incretins have been made in many cases outside the regulatory limits. Nevertheless, when appropriately utilized, incretins may grant results at least in line with pivotal trials.

Topics: Adamantane; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Utilization; Drug-Related Side Effects and Adverse Reactions; Exenatide; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Italy; Male; Metformin; Middle Aged; Monitoring, Physiologic; Nitriles; Peptides; Pyrazines; Pyrrolidines; Registries; Sex Factors; Sitagliptin Phosphate; Triazoles; Venoms; Vildagliptin

Topics: Adverse Drug Reaction Reporting Systems; Drug Approval; Drug Industry; Drug-Related Side Effects and Adverse Reactions; Marketing; Pyrazines; Sitagliptin Phosphate; Time Factors; Triazoles