sitagliptin-phosphate and Renal-Insufficiency

To compare the efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin with the sodium-glucose transporter-2 inhibitor dapagliflozin in patients with type 2 diabetes and mild renal insufficiency.. In patients with type 2 diabetes, mild renal insufficiency and inadequate glycaemic control on metformin ± sulfonylurea, sitagliptin treatment resulted in greater improvement in glycaemic control compared with dapagliflozin and was generally well tolerated.

Topics: Adult; Aged; Benzhydryl Compounds; Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glomerular Filtration Rate; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Kidney; Least-Squares Analysis; Male; Middle Aged; Postprandial Period; Renal Insufficiency; Sitagliptin Phosphate; Treatment Outcome

To evaluate weekly subcutaneous albiglutide versus daily sitagliptin in renally impaired patients with type 2 diabetes and inadequately controlled glycemia on a regimen of diet and exercise and/or oral antihyperglycemic medications.. In this phase III, randomized, double-blind, multicenter, 52-week study, the primary study end point was HbA1c change from baseline at week 26 in patients with renal impairment, as assessed with estimated glomerular filtration rate and categorized as mild, moderate, or severe (≥60 to ≤89, ≥30 to ≤59, and ≥15 to ≤29 mL/min/1.73 m(2), respectively). Secondary end points included fasting plasma glucose (FPG), weight, achievement of treatment targets, hyperglycemic rescue, and safety.. Baseline demographics were similar across treatment and renal impairment groups with overall mean age of 63.3 years, BMI of 30.4 kg/m(2), HbA1c of 8.2% (66 mmol/mol), and diabetes disease duration of 11.2 years. HbA1c change from baseline at week 26 was significantly greater for albiglutide than sitagliptin (-0.83% vs. -0.52%, P = 0.0003). Decreases in HbA1c, FPG, and weight were seen through week 52. Time to hyperglycemic rescue through week 52 was significantly longer for albiglutide than sitagliptin (P = 0.0017). Results of safety assessments were similar between groups, and most adverse events (AEs) were mild or moderate. The incidences of gastrointestinal AEs for albiglutide and sitagliptin were as follows: overall, 31.7%, 25.2%; diarrhea, 10.0%, 6.5%; nausea, 4.8%, 3.3%; and vomiting, 1.6%, 1.2%, respectively.. Once-weekly albiglutide therapy in renally impaired patients with type 2 diabetes provided statistically superior glycemic improvement with almost similar tolerability compared with daily sitagliptin therapy.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Double-Blind Method; Drug Administration Schedule; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Male; Middle Aged; Pyrazines; Receptors, Glucagon; Renal Insufficiency; Sitagliptin Phosphate; Treatment Outcome; Triazoles

Methotrexate (MTX), a cytotoxic chemotherapeutic and immunosuppressant agent, is widely used in the treatment of autoimmune diseases and different types of cancers. However, its use has been limited by its life-threatening side effects, including nephrotoxicity and hepatotoxicity. The purpose of this study was to investigate the protective effect of sitagliptin on methotrexate (MTX)-induced nephrotoxicity in rats. Twenty-four rats were divided into four groups: control group, which received the vehicle for 6 days; MTX group, which received a single dose of MTX, followed by five daily doses of vehicle dosing; MTX + sitagliptin group, which received a single dose of MTX 1 h after the first sitagliptin treatment and six daily doses of sitagliptin; and sitagliptin group, which received sitagliptin for 6 days. Both MTX and sitagliptin were given as intraperitoneal injections at a dose of 20 mg/kg body weight. All rats were euthanized on the seventh day of the study. Kidney tissues were harvested and blood samples were collected. Serum levels of blood urea nitrogen (BUN) and creatinine were evaluated. Furthermore, catalase, glutathione peroxidase, superoxide dismutase activities, and malondialdehyde (MDA) levels were determined in kidney tissue. In addition, histopathological analysis was conducted. Histopathological evaluation showed that MTX-induced marked kidney injury. Biochemical analysis revealed a significant increase of BUN and creatinine in the serum of the MTX group. Furthermore, oxidative stress and depressed antioxidant system of the kidney tissues were evident in the MTX group. Sitagliptin did not affect these endpoints when administered alone, but it significantly attenuated the observed MTX-induced effects. These results suggest that sitagliptin exhibits potent anti-oxidant properties against the nephrotoxicity induced by MTX in rats.

Topics: Animals; Antioxidants; Creatinine; Kidney; Methotrexate; Rats; Renal Insufficiency; Sitagliptin Phosphate

A measure correlating the time course of the effect with the time course of concentrations could be helpful in drug dosing. We propose a new equation with explicit solutions for calculating the effect duration. A specific effect fraction is selected (fr) and the time of fractional effect duration (TED.fr) can be derived as a function of the elimination half-life by combining linear elimination kinetics with sigmoid effect dynamics. This new measure is applied to the example of sitagliptin, whose elimination half-life increases from 10.1 to 28.4 h in patients with kidney failure. Under normal multiple-dose conditions, the 24-h sitagliptin administration interval corresponds to a 0.90 time of fractional effect duration (TED.90). A dose reduction to one-fourth or 25 mg every 24 h is proposed for patients with kidney failure; this results in a TED.90 of 45 h, i.e. 21 h longer than the proposed 24-h administration interval (+88 %). The proportional dosing alternative of 100 mg every 96 h would result in a TED.90 of 64 h, which is 32 h less than the 96-h administration interval (-33 %). With a half dose of 50 mg and a doubled administration interval of 48 h, the TED.90 is 51 h in kidney failure, only 3 h longer than the latter administration interval (+6 %). We conclude that our general equation can be applied to rapidly calculate the specific time of effect duration for the different dose schedules.

Topics: Half-Life; Humans; Pyrazines; Renal Insufficiency; Sitagliptin Phosphate; Time Factors; Triazoles

Sitagliptin (Januvia) was the first selective inhibitor of dipeptidyl peptidase-4 commercialized for the management of type 2 diabetes. It is also available as a fixed-dose combination with meformin (Janumet). Almost 5 years after its launch in Belgium, the present review summarizes the most recent data regarding the clinical efficacy of this antidiabetic agent, the controversy about its safety profile, its use at lower dosage in case of moderate to severe renal insufficiency, the various indications that have been successively accepted and reimbursed, and, finally, the perspectives offered by a large ongoing cardiovascular outcome trial (TECOS).

Topics: Belgium; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Dose-Response Relationship, Drug; Drug Combinations; Humans; Hypoglycemic Agents; Metformin; Pyrazines; Renal Insufficiency; Sitagliptin Phosphate; Sitagliptin Phosphate, Metformin Hydrochloride Drug Combination; Triazoles

Topics: Aged; Dipeptidyl-Peptidase IV Inhibitors; Female; Humans; Pyrazines; Renal Insufficiency; Sitagliptin Phosphate; Triazoles

Topics: Amiodarone; Contraindications; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Liver-Specific Organic Anion Transporter 1; Male; Organic Anion Transporters; Pyrazines; Renal Insufficiency; Rhabdomyolysis; Simvastatin; Sitagliptin Phosphate; Triazoles; United Kingdom; United States

Sitagliptin is recommended for initial and maintenance dosing at 100 mg daily. Downward dose adjustment is recommended in patients with moderate or severe renal insufficiency.. To determine the prevalence of the potentially inappropriate initial dosing of sitagliptin based on estimated glomerular filtration rate (GFR) at baseline for pharmacist versus nonpharmacist prescribers in an internal medicine department of a private physician-owned multispecialty clinic that included a pharmacist-managed diabetes program.. This was a retrospective cross-sectional cohort analysis using data from an electronic medical record database of a private physicianowned multispecialty clinic that included a pharmacist-managed diabetes program. For patients prescribed sitagliptin between October 17, 2006, and June 5, 2008, the variables of interest were (a) the initial sitagliptin dose; (b) the GFR, calculated for each patient using the 4-point Modification of Dosing in Renal Disease (MDRD) formula at the time of initiation of sitagliptin; and (c) whether the clinician initiating the dose was a pharmacist or nonpharmacist (i.e., internal medicine physician, nurse practitioner, or physician assistant).. Of the 290 patients prescribed sitagliptin for the first time between October 17, 2006, and June 5, 2008, 35 (12.1%) received a potentially inappropriate initial dose according to product labeling regarding renal function; 21 were over-dosed and 14 were under-dosed. Potentially inappropriate dosing occurred in 1 of 158 patients (0.6%) who had initial dosing prescribed by a pharmacist compared with 34 of 132 patients (25.8%) for nonpharmacists (P < 0.001, Fisher's exact test).. Potentially inappropriate initial dosing of sitagliptin based on assessment of renal function was more likely to occur with nonpharmacist prescribers than with a pharmacist prescriber.

Topics: Ambulatory Care Facilities; Cohort Studies; Cross-Sectional Studies; Databases, Factual; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Monitoring; Drug Utilization Review; Glomerular Filtration Rate; Humans; Hypoglycemic Agents; Kidney Function Tests; Medication Errors; Pharmacists; Private Sector; Professional Role; Pyrazines; Renal Insufficiency; Retrospective Studies; Sitagliptin Phosphate; Triazoles; United States

Topics: Adolescent; Adult; Aged; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Female; Humans; Hypoglycemic Agents; Male; Middle Aged; Pyrazines; Renal Insufficiency; Sitagliptin Phosphate; Triazoles