Animals ; Autophagy ; Diabetes Mellitus, Experimental/drug therapy* ; Mice ; Myocardium ; Sitagliptin Phosphate/pharmacology* ; Streptozocin

Animals ; Blood Glucose ; Diabetes Mellitus, Type 2/drug therapy* ; Insulin ; Insulin Resistance ; Islets of Langerhans ; Metformin/pharmacology* ; Mice ; Prediabetic State ; Sitagliptin Phosphate/pharmacology*

OBJECTIVES: This study was performed to clarify the effects of sitagliptin on METHODS: Healthy gingival samples were collected from the donors. HGFs were isolated with enzymic digestion method and identified. The effects of LPS and sitagliptin on cell viability were detected by cell-counting kit-8 (CCK8). The mRNA levels of inflammatory cytokines, namely, interleukin (IL)-6, IL-8, C-C motif ligand 2 (CCL2), and superoxide dismutase 2 (SOD2), were evaluated by quantity real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immune sorbent assay (ELISA) was used to measure the secretion protein levels of IL-6, IL-8, and CCL2. Western blot analysis was used to further investigate the activation of nuclear factor (NF)-κB signaling pathway. The effect of NF-κB pathway inhibitor BAY11-7082 on LPS-induced HGF inflammatory cytokines at the gene level was verified by qRT-PCR. RESULTS: Low concentrations of sitagliptin (0.1, 0.25, and 0.5 µmol·L CONCLUSIONS Sitagliptin could significantly inhibit LPS-induced HGF inflammatory response by blocking the NF-κB signaling pathway activation.
Fibroblasts ; Gingiva/metabolism* ; Humans ; Lipopolysaccharides ; NF-kappa B/metabolism* ; Signal Transduction ; Sitagliptin Phosphate

BACKGROUND: We evaluated the efficacy and safety of acarbose add-on therapy in Korean patients with type 2 diabetes mellitus (T2DM) who are inadequately controlled with metformin and sitagliptin. METHODS: A total of 165 subjects were randomized to metformin and sitagliptin (Met+Sita, n=65), metformin, sitagliptin, and acarbose (Met+Sita+Acarb, n=66) and sitagliptin and acarbose (Sita+Acarb, exploratory assessment, n=34) therapy in five institutions in Korea. After 16 weeks of acarbose add-on or metformin-switch therapy, a triple combination therapy was maintained from week 16 to 24. RESULTS: The add-on of acarbose (Met+Sita+Acarb group) demonstrated a 0.44%±0.08% (P<0.001 vs. baseline) decrease in glycosylated hemoglobin (HbA1c) at week 16, while changes in HbA1c were insignificant in the Met+Sita group (−0.09%±0.10%, P=0.113). After 8 weeks of triple combination therapy, HbA1c levels were comparable between Met+Sita and Met+Sita+Acarb group (7.66%±0.13% vs. 7.47%±0.12%, P=0.321). Acarbose add-on therapy demonstrated suppressed glucagon secretion (area under the curve of glucagon, 4,726.17±415.80 ng·min/L vs. 3,314.38±191.63 ng·min/L, P=0.004) in the absence of excess insulin secretion during the meal tolerance tests at week 16 versus baseline. The incidence of adverse or serious adverse events was similar between two groups. CONCLUSION: In conclusion, a 16-week acarbose add-on therapy to metformin and sitagliptin, effectively lowered HbA1c without significant adverse events. Acarbose might be a good choice as a third-line therapy in addition to metformin and sitagliptin in Korean subjects with T2DM who have predominant postprandial hyperglycemia and a high carbohydrate intake.
Acarbose ; Diabetes Mellitus, Type 2 ; Drug Therapy, Combination ; Glucagon ; Hemoglobin A, Glycosylated ; Humans ; Hyperglycemia ; Incidence ; Insulin ; Korea ; Meals ; Metformin ; Sitagliptin Phosphate

PURPOSE: Cardiovascular adverse events (AEs) after use of dipeptidyl peptidase-4 (DPP4) inhibitors have been reported and suspected since the launch of DPP-4 inhibitors in 2006. However, few studies have investigated the association between cardiovascular AEs and DPP-4 inhibitors. The objective of this study is to detect the signals of cardiovascular AEs after use of DPP-4 inhibitors by analyzing the Korea Institute of Drug Safety & Risk Management-Korea Adverse Event Reporting System Database (KIDS-KD). MATERIALS AND METHODS: Data on the use of oral antidiabetic drugs from 2008 to 2016 were extracted from KIDS-KD, and analyzed descriptively. Data mining was conducted by calculating three indices, which were proportional reporting ratios, reporting odds ratios, and information components, to detect signals from use of all oral antidiabetic drugs including DPP-4 inhibitors. Then, the suspected adverse drug reactions (ADRs) were confirmed by signal detection, and drug label information between the Korea Ministry of Food and Drug Safety and the U.S. Food and Drug Administration were compared. RESULTS: Cardiovascular AEs after taking DPP-4 inhibitors were detected in only three (1.0%) out of a total of 307 AE reports. Two of the three cardiovascular AEs were reported after using sitagliptin and one using gemiglipitin, but these were not statistically significant. CONCLUSION: Analysis of spontaneous ADR reports data on the use of DPP-4 inhibitors could not showed the association between DPP-4 inhibitors and cardiovascular AEs, due to a small number of cardiovascular AEs reports.
Cardiovascular Diseases ; Data Mining ; Drug-Related Side Effects and Adverse Reactions ; Hypoglycemic Agents ; Korea ; Odds Ratio ; Pharmacovigilance ; Sitagliptin Phosphate ; United States Food and Drug Administration

BACKGROUND AND OBJECTIVES: To compare cardiovascular disease (CVD) risk associated with 5 different dipeptidyl peptidase-4 inhibitors (DPP-4is) in people with type 2 diabetes. METHODS: We identified 534,327 people who were newly prescribed sitagliptin (n=167,157), vildagliptin (n=67,412), saxagliptin (n=29,479), linagliptin (n=220,672), or gemigliptin (n=49,607) between January 2013 and June 2015 using the claims database of the Korean National Health Insurance System. A Cox proportional hazards model was used to estimate hazard ratios (HRs) for major CVD events (myocardial infarction, stroke, or death) among users of different DPP-4is. The model was adjusted for sex, age, duration of DPP-4i use, use of other glucose-lowering drugs, use of antiplatelet agents, hypertension, dyslipidemia, atrial fibrillation, chronic kidney disease, microvascular complications of diabetes, Charlson comorbidity index, and the calendar index year as potential confounders. RESULTS: Compared to sitagliptin users, the fully adjusted HRs for CVD events were 0.97 (95% confidence interval [CI], 0.94–1.01; p=0.163) for vildagliptin, 0.76 (95% CI, 0.71–0.81; p < 0.001) for saxagliptin, 0.95 (95% CI, 0.92–0.98; p < 0.001) for linagliptin, and 0.84 (95% CI, 0.80–0.88; p < 0.001) for gemigliptin. CONCLUSIONS: Compared to sitagliptin therapy, saxagliptin, linagliptin, and gemigliptin therapies were all associated with a lower risk of cardiovascular events.
Atrial Fibrillation ; Cardiovascular Diseases ; Comorbidity ; Diabetes Mellitus, Type 2 ; Dipeptidyl-Peptidase IV Inhibitors ; Dyslipidemias ; Hypertension ; Infarction ; Korea ; Linagliptin ; National Health Programs ; Platelet Aggregation Inhibitors ; Proportional Hazards Models ; Renal Insufficiency, Chronic ; Sitagliptin Phosphate ; Stroke

Dipeptidyl peptidase4 (DPP4) inhibitors such as gemigliptin are anti-diabetic drugs elevating plasma concentration of incretins such as GLP-1. In addition to the DPP4 inhibition, gemigliptin might directly improve the functions of vessels under pathological conditions. To test this hypothesis, we investigated whether the acetylcholine-induced endothelium dependent relaxation (ACh-EDR) of mesenteric arteries (MA) are altered by gemigliptin pretreatment in Spontaneous Hypertensive Rats (SHR) and in Wistar-Kyoto rats (WKY) under hyperglycemia-like conditions (HG; 2 hr incubation with 50 mM glucose). ACh-EDR of WKY was reduced by the HG condition, which was significantly recovered by 1 µM gemigliptin while not by saxagliptin and sitagliptin up to 10 µM. The ACh-EDR of SHR MA was also improved by 1 µM gemigliptin while similar recovery was observed with higher concentration (10 µM) of saxagliptin and sitagliptin. The facilitation of ACh-EDR by gemigliptin in SHR was not observed under pretreatment with NOS inhibitor, L-NAME. In the endotheliumdenuded MA of SHR, sodium nitroprusside induced dose-dependent relaxation was not affected by gemigliptin. The ACh-EDR in WKY was decreased by treatment with 30 µM pyrogallol, a superoxide generator, which was not prevented by gemigliptin. Exendin-4, a GLP-1 analogue, could not enhance the ACh-EDR in SHR MA. The present results of ex vivo study suggest that gemigliptin enhances the NOS-mediated EDR of the HG-treated MA as well as the MA from SHR via GLP-1 receptor independent mechanism.
Animals ; Endothelium ; Glucagon-Like Peptide 1 ; Glucagon-Like Peptide-1 Receptor ; Hyperglycemia ; Hypertension ; Incretins ; Mesenteric Arteries* ; NG-Nitroarginine Methyl Ester ; Nitroprusside ; Plasma ; Pyrogallol ; Rats ; Rats, Inbred SHR* ; Relaxation ; Sitagliptin Phosphate ; Superoxides ; Vasodilation*

No abstract available.
Non-alcoholic Fatty Liver Disease* ; Sitagliptin Phosphate* ; Synbiotics*

BACKGROUND/AIMS: Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases in recent years. The aim of this study was to evaluate the effects of sitagliptin with and without a synbiotic supplement in the treatment of patients with NAFLD. METHODS: In total, 138 NAFLD patients aged 18-60 years were enrolled in the study. Patients were randomized to one of the following treatments for 16 weeks: Group I (n=68), sitagliptin 50 mg daily plus placebo (one capsule per day) or group II (n=70) sitagliptin 50 mg daily plus synbiotic (one capsule per day). Changes in fasting blood glucose (FBS), liver enzymes, lipid profile, and body mass index were compared between the groups. RESULTS: The mean change in FBS with sitagliptin-placebo from baseline was -10.47±5.77 mg/dL, and that with sitagliptin-synbiotic was -13.52±4.16 mg/dL. There was a significant difference between the groups (P < 0.001). The mean change in cholesterol (Chol) was -8.34±28.83 mg/dL with sitagliptin-placebo and -21.25±15.50 mg/dL with sitagliptinsynbiotic. There was a significant difference between the two groups (P=0.029). The administration of sitagliptin-placebo induced an increase of 6.13±27.04 mg/dL in low density lipoprotein (LDL), whereas sitagliptin-synbiotic induced a decrease of 14.92±15.85 mg/dL in LDL. A significant difference was observed between the two groups (P < 0.001). On the other hand, in the sitagliptin-synbiotic group, there was significant improvement in aspartate aminotransferase (AST) level compared to the sitagliptin-placebo group (P=0.018). CONCLUSIONS: Sitagliptin-synbiotic produced greater improvement in FBS, AST, Chol, and LDL compared to sitagliptin alone in patients with NAFLD.
Aspartate Aminotransferases ; Blood Glucose ; Body Mass Index ; Cholesterol ; Fasting ; Hand ; Humans ; Lipoproteins ; Liver ; Liver Diseases ; Non-alcoholic Fatty Liver Disease* ; Sitagliptin Phosphate* ; Synbiotics*

INTRODUCTIONWe aimed to evaluate the effectiveness and safety of canagliflozin as compared to sitagliptin in a real-world setting among multiethnic patients with Type 2 diabetes mellitus (T2DM) in Singapore.

METHODSThis was a new-user, active-comparator, single-centre retrospective cohort study. Patients aged 18-69 years with T2DM and estimated glomerular filtration rate ≥ 60 mL/min/1.73 m were eligible for inclusion if they were initiated and maintained on a steady daily dose of canagliflozin 300 mg or sitagliptin 100 mg between 1 May and 31 December 2014, and followed up for 24 weeks.

RESULTSIn total, 57 patients (canagliflozin 300 mg, n = 22; sitagliptin 100 mg, n = 35) were included. The baseline patient characteristics in the two groups were similar, with overall mean glycated haemoglobin (HbA1c) of 9.4% ± 1.4%. The use of canagliflozin 300 mg was associated with greater reductions in HbA1c (least squares [LS] mean change -1.6% vs. -0.4%; p < 0.001), body weight (LS mean change -3.0 kg vs. 0.2 kg; p < 0.001) and systolic blood pressure (LS mean change: -9.7 mmHg vs. 0.4 mmHg; p < 0.001), as compared with sitagliptin 100 mg. About half of the patients on canagliflozin 300 mg reported mild osmotic diuresis-related side effects that did not lead to drug discontinuation.

CONCLUSIONOur findings suggest that canagliflozin was more effective than sitagliptin in reducing HbA1c, body weight and systolic blood pressure in patients with T2DM, although its use was associated with an increased incidence of mild osmotic diuresis-related side effects.

Adolescent ; Adult ; Aged ; Blood Glucose ; drug effects ; Blood Pressure ; Body Mass Index ; Body Weight ; Canagliflozin ; administration & dosage ; Diabetes Mellitus, Type 2 ; drug therapy ; Female ; Glomerular Filtration Rate ; Hemoglobins ; analysis ; Humans ; Hypoglycemic Agents ; administration & dosage ; Least-Squares Analysis ; Male ; Middle Aged ; Osmosis ; Retrospective Studies ; Singapore ; Sitagliptin Phosphate ; administration & dosage ; Systole ; Treatment Outcome ; Young Adult