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SITAGLIPTIN

Alias: EC 690-730-1; HSDB 7516; HSDB7516; HSDB-7516; Januvia; LEZ 763; LEZ-763; LEZ763; Tesavel; Xelevia; (R)-3-AMINO-1-(3-(TRIFLUOROMETHYL)-5,6-DIHYDRO-[1,2,4]TRIAZOLO[4,3-A]PYRAZIN-7(8H)-YL)-4-(2,4,5-TRIFLUOROPHENYL)BUTAN-1-ONE; sitagliptina; MK-0431; MK0431; MK 0431; MK-431; MK431; MK 431; Sitagliptin Phosphate; Sitagliptin Phosphate Monohydrate; trade name: Januvia Xelevia Janumet
Cat No.:V4388 Purity: ≥98%
Sitagliptin (formerly also known as MK-431; trade name Januvia), an antihyperglycemic agent and a antidiabetic drug, is a potent, orally bioavailable inhibitor of DPP-IV (dipeptidyl peptidase-4) with IC50 of 19 nM in Caco-2 cell extracts.
SITAGLIPTIN
SITAGLIPTIN Chemical Structure CAS No.: 486460-32-6
Product category: DPP-4
This product is for research use only, not for human use. We do not sell to patients.
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100mg
250mg
500mg
1g
2g
5g
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Other Sizes

Other Forms of SITAGLIPTIN:

  • 3-Trifluoromethyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride (Intermediate Ⅰ of sitagliptin phosphate)
  • (S)-Sitagliptin phosphate ((S)-MK-0431 phosphate)
  • Sitagliptin phosphate
  • Sitagliptin phosphate monohydrate
  • (Rac)-Sitagliptin ((Rac)-MK-0431)
  • Sitagliptin-d4 hydrochloride (MK-0431-d4 hydrochloride)
Official Supplier of:
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Sitagliptin (formerly also known as MK-431; trade name Januvia), an antihyperglycemic agent and aantidiabetic drug, is a potent, orally bioavailable inhibitor of DPP-IV (dipeptidyl peptidase-4) with IC50 of 19 nM in Caco-2 cell extracts. It is an enzyme-inhibiting medication used to treat type 2 diabetes. It can be taken either by itself or in conjunction with other oral antihyperglycemic medications like metformin or thiazolidinedione. One advantage of this medication is that it controls blood glucose levels with fewer side effects (such as hypoglycemia and weight gain). By influencing the incretin system, exenatide (Byetta) also functions.

Biological Activity I Assay Protocols (From Reference)
Targets
DPP-4 (IC50 = 18 nM)
ln Vitro
Sitagliptin phosphate shows a strong inhibitory action on DPP-4 from extracts of Caco-2 cells, with an IC50 of 19 nM[1]. Via a mechanism involving cAMP/PKA/Rac1 activation, sitagliptin decreases the in vitro migration of isolated splenic CD4 T-cells[2]. A recent study shows that sitagliptin stimulates intestinal L cell GLP-1 secretion through a novel, direct action that is dependent on MEK-ERK1/2 and protein kinase A, but not on DPP-4. As a result, it lessens the impact of autoimmunity on graft survival[3].
ln Vivo
For sitagliptin phosphate to inhibit plasma DPP-4 activity in vivo, the ED50 value in freely fed Han-Wistar rats is estimated to be 2.3 mg/kg seven hours postdose and 30 mg/kg twenty-four hours postdose[1]. Elevated DPP-4 levels in the plasma are seen in the streptozotocin-induced type 1 diabetes mouse model, but these levels can be significantly reduced in mice fed Sitagliptin phosphate. This is accomplished by possibly prolonging islet graft survival through a beneficial effect on the regulation of hyperglycemia[4]. Sitagliptin phosphate's plasma clearance and volume of distribution are higher in rats (40–48 mL/min/kg, 7-9 L/kg) than in dogs (9 mL/min/kg, 3 L/kg); additionally, rats' half-lives are shorter—two hours versus four hours in dogs[5].
Enzyme Assay
Confluent Caco-2 cells are used to extract DPP-4. Following a 5-minute room temperature incubation period with lysis buffer (10 mM Tris-HCl, 150 mM NaCl, 0.04 U/mL aprotinin, 0.5% Nonidet P40, pH 8.0), the cells are centrifuged at 35,000 g for 30 minutes at 4 °C, and the supernatant is kept at -80°C afterwards. Twenty microliters of suitable compound dilutions are combined with fifty microliters of H-Ala-Pro-7-amido-4-trifluoromethylcoumarin (final concentration in the assay: 100 microliters) as the substrate for the DPP-4 enzyme, and thirty microliters of the Caco-2 cell extract (diluted 1000 times with 100 mM Tris-HCl, 100 mM NaCl, pH 7.8). Fluorescence is measured using a SpectraMax GeminiXS at excitation/emission wavelengths of 405/535 nm after plates are incubated for one hour at room temperature. After exposing Caco-2 cell extracts to high inhibitor concentrations (30 nM for BI 1356 and 3 μM for vildagliptin) for one hour, the dissociation kinetics of the inhibitors from the DPP-4 enzyme are ascertained. Once the preincubation mixture has been diluted 3000-fold with assay buffer, the enzymatic reaction is initiated by adding the substrate, H-Ala-Pro-7-amido-4-trifluoromethylcoumarini. The amount of an inhibitor that is still bound to the DPP-4 enzyme is indicated by the difference in DPP-4 activity at a given time in the presence or absence of the inhibitor. Using the SoftMax software of the SpectraMax, maximum reaction rates (fluorescence units/seconds × 1000) are calculated at 10-minute intervals and corrected for the rate of an uninhibited reaction [(vcontrol-vinhibitor)/vcontrol].
Cell Assay
Membrane inserts containing CD4T-cells are plated in serum-free RPMI 1640. Cell migration is measured using Corning Transwell chambers, either with or without DPP-4 inhibitor (100 μM) and purified porcine kidney DPP-4 (32.1 units/mg; final concentration of 100 mU/mL). Following an hour, cells that have moved into the lower compartment are counted and those on the upper surface are mechanically removed. The expression for the amount of migration is in relation to the control sample.
Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted into the circulation by the intestinal L cell. The dipeptidylpeptidase-IV (DPP-IV) inhibitor, sitagliptin, prevents GLP-1 degradation and is used in the clinic to treat patients with type 2 diabetes mellitus, leading to improved glycated hemoglobin levels. When the effect of sitagliptin on GLP-1 levels was examined in neonatal streptozotocin rats, a model of type 2 diabetes mellitus, a 4.9 ± 0.9-fold increase in basal and 3.6 ± 0.4-fold increase in oral glucose-stimulated plasma levels of active GLP-1 was observed (P < 0.001), in association with a 1.5 ± 0.1-fold increase in the total number of intestinal L cells (P < 0.01). The direct effects of sitagliptin on GLP-1 secretion and L cell signaling were therefore examined in murine GLUTag (mGLUTag) and human hNCI-H716 intestinal L cells in vitro. Sitagliptin (0.1-2 μM) increased total GLP-1 secretion by mGLUTag and hNCI-H716 cells (P < 0.01-0.001). However, MK0626 (1-50 μM), a structurally unrelated inhibitor of DPP-IV, did not affect GLP-1 secretion in either model. Treatment of mGLUTag cells with the GLP-1 receptor agonist, exendin-4, did not modulate GLP-1 release, indicating the absence of feedback effects of GLP-1 on the L cell. Sitagliptin increased cAMP levels (P < 0.01) and ERK1/2 phosphorylation (P < 0.05) in both mGLUTag and hNCI-H716 cells but did not alter either intracellular calcium or phospho-Akt levels. Pretreatment of mGLUTag cells with protein kinase A (H89 and protein kinase inhibitor) or MAPK kinase-ERK1/2 (PD98059 and U0126) inhibitors prevented sitagliptin-induced GLP-1 secretion (P < 0.05-0.01). These studies demonstrate, for the first time, that sitagliptin exerts direct, DPP-IV-independent effects on intestinal L cells, activating cAMP and ERK1/2 signaling and stimulating total GLP-1 secretion[3].
Animal Protocol
Mice: C57BL/6J mice that have been fasted overnight are challenged with an oral glucose load (2 g/kg) 45 minutes after the compound is administered. Tail bleed predose and successive time points following the glucose load are used to draw blood samples for glucose measurement. DPP-4 inhibitors or a vehicle are given 16 hours prior to the glucose challenge in order to assess how long the effect lasts on glucose tolerance.
Effects of MK0431 on islet graft survival in diabetic NOD mice were determined with metabolic studies and micropositron emission tomography imaging, and its underlying molecular mechanisms were assessed.
Results: Treatment of NOD mice with MK0431 before and after islet transplantation resulted in prolongation of islet graft survival, whereas treatment after transplantation alone resulted in small beneficial effects compared with nontreated controls. Subsequent studies demonstrated that MK0431 pretreatment resulted in decreased insulitis in diabetic NOD mice and reduced in vitro migration of isolated splenic CD4+ T-cells. Furthermore, in vitro treatment of splenic CD4+ T-cells with DPP-IV resulted in increased migration and activation of protein kinase A (PKA) and Rac1.
Conclusions: Treatment with MK0431 therefore reduced the effect of autoimmunity on graft survival partially by decreasing the homing of CD4+ T-cells into pancreatic beta-cells through a pathway involving cAMP/PKA/Rac1 activation.[2]
Effects of the DPP-IV inhibitor MK0431 (sitagliptin) on glycemic control and functional islet mass in a streptozotocin (STZ)-induced type 1 diabetes mouse model were determined with metabolic studies and microPET imaging.
Results: The type 1 diabetes mouse model exhibited elevated plasma DPP-IV levels that were substantially inhibited in mice on an MK0431 diet. Residual beta-cell mass was extremely low in STZ-induced diabetic mice, and although active GLP-1 levels were increased by the MK0431 diet, there were no significant effects on glycemic control. After islet transplantation, mice fed normal diet rapidly lost their ability to regulate blood glucose, reflecting the suboptimal islet transplant. By contrast, the MK0431 group fully regulated blood glucose throughout the study, and PET imaging demonstrated a profound protective effect of MK0431 on islet graft size.
Conclusions: Treatment with a DPP-IV inhibitor can prolong islet graft retention in an animal model of type 1 diabetes.[4]
The pharmacokinetics, metabolism, and excretion of sitagliptin [MK-0431; (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine], a potent dipeptidyl peptidase 4 inhibitor, were evaluated in male Sprague-Dawley rats and beagle dogs. The plasma clearance and volume of distribution of sitagliptin were higher in rats (40-48 ml/min/kg, 7-9 l/kg) than in dogs ( approximately 9 ml/min/kg, approximately 3 l/kg), and its half-life was shorter in rats, approximately 2 h compared with approximately 4 h in dogs. Sitagliptin was absorbed rapidly after oral administration of a solution of the phosphate salt. The absolute oral bioavailability was high, and the pharmacokinetics were fairly dose-proportional. After administration of [(14)C]sitagliptin, parent drug was the major radioactive component in rat and dog plasma, urine, bile, and feces. Sitagliptin was eliminated primarily by renal excretion of parent drug; biliary excretion was an important pathway in rats, whereas metabolism was minimal in both species in vitro and in vivo. Approximately 10 to 16% of the radiolabeled dose was recovered in the rat and dog excreta as phase I and II metabolites, which were formed by N-sulfation, N-carbamoyl glucuronidation, hydroxylation of the triazolopiperazine ring, and oxidative desaturation of the piperazine ring followed by cyclization via the primary amine. The renal clearance of unbound drug in rats, 32 to 39 ml/min/kg, far exceeded the glomerular filtration rate, indicative of active renal elimination of parent drug.[5]
ADME/Pharmacokinetics
Absorption, Distribution and Excretion
Sitagliptin is 87% orally bioavailable and taking it with or without food does not affect its pharmacokinetics. Sitagliptin reaches maximum plasma concentration in 2 hours.
Approximately 79% of sitagliptin is excreted in the urine as the unchanged parent compound. 87% of the dose is eliminated in the urine and 13% in the feces.
198L.
350mL/min.
Sitagliptin is secreted in the milk of lactating rats at a milk to plasma ratio of 4:1. It is not known whether sitagliptin is excreted in human milk.
Placental transfer of sitagliptin administered to pregnant rats was approximately 45% at 2 hours and 80% at 24 hours postdose. Placental transfer of sitagliptin administered to pregnant rabbits was approximately 66% at 2 hours and 30% at 24 hours.
Approximately 79% of sitagliptin is excreted unchanged in the urine with metabolism being a minor pathway of elimination.
Elimination of sitagliptin occurs primarily via renal excretion and involves active tubular secretion. Sitagliptin is a substrate for human organic anion transporter-3 (hOAT-3), which may be involved in the renal elimination of sitagliptin. The clinical relevance of hOAT-3 in sitagliptin transport has not been established. Sitagliptin is also a substrate of p-glycoprotein, which may also be involved in mediating the renal elimination of sitagliptin. However, cyclosporine, a p-glycoprotein inhibitor, did not reduce the renal clearance of sitagliptin.
For more Absorption, Distribution and Excretion (Complete) data for SITAGLIPTIN (10 total), please visit the HSDB record page.
Metabolism / Metabolites
Sitagliptin is mostly not metabolised, with 79% of the dose excreted in the urine as the unchanged parent compound. Minor metabolic pathways are mediated mainly by cytochrome p450(CYP)3A4 and to a lesser extent by CYP2C8. After 18 hours, 81% of the dose has remained unchanged, while 2% has been N-sulfated to the M1 metabolite, 6% has been oxidatively desaturated and cyclized to the M2 metabolite, <1% glucuronidated at an unknown site to the M3 metabolite, <1% has been carbamoylated and glucuronidated to the M4 metabolite, 6% has been oxidatively saturated and cyclized to the M5 metabolite, and 2% has been hydroxylated at an unknown site to the M6 metabolite. The M2 metabolite is the cis isomer while the M5 metabolite is the trans isomer of the same metabolite.
The metabolism and excretion of (14)C sitagliptin ... were investigated in humans after a single oral dose of 83 mg/193 muCi. Urine, feces, and plasma were collected at regular intervals for up to 7 days. The primary route of excretion of radioactivity was via the kidneys, with a mean value of 87% of the administered dose recovered in urine. Mean fecal excretion was 13% of the administered dose. Parent drug was the major radioactive component in plasma, urine, and feces, with only 16% of the dose excreted as metabolites (13% in urine and 3% in feces), indicating that sitagliptin was eliminated primarily by renal excretion. Approximately 74% of plasma AUC of total radioactivity was accounted for by parent drug. Six metabolites were detected at trace levels, each representing <1 to 7% of the radioactivity in plasma. These metabolites were the N-sulfate and N-carbamoyl glucuronic acid conjugates of parent drug, a mixture of hydroxylated derivatives, an ether glucuronide of a hydroxylated metabolite, and two metabolites formed by oxidative desaturation of the piperazine ring followed by cyclization. These metabolites were detected also in urine, at low levels. Metabolite profiles in feces were similar to those in urine and plasma, except that the glucuronides were not detected in feces. CYP3A4 was the major cytochrome P450 isozyme responsible for the limited oxidative metabolism of sitagliptin, with some minor contribution from CYP2C8.
Following a (14)C sitagliptin oral dose, approximately 16% of the radioactivity was excreted as metabolites of sitagliptin. Six metabolites were detected at trace levels and are not expected to contribute to the plasma DPP-4 inhibitory activity of sitagliptin. In vitro studies indicated that the primary enzyme responsible for the limited metabolism of sitagliptin was CYP3A4, with contribution from CYP2C8.
Biological Half-Life
Approximately 12.4 hours. Other studies have reported a half life of approximately 11 hours.
Two double-blind, randomized, placebo-controlled, alternating-panel studies evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of single oral doses of sitagliptin (1.5-600 mg) in healthy male volunteers. Sitagliptin was well absorbed (approximately 80% excreted unchanged in the urine) with an apparent terminal half-life ranging from 8 to 14 hours. ...
The apparent terminal half life following a 100 mg oral dose of sitagliptin was approximately 12.4 hours ... .
Toxicity/Toxicokinetics
Toxicity Summary
IDENTIFICATION AND USE: Sitagliptin is a viscous liquid. It is a dipeptidyl peptidase-4 inhibitor and used to improve glycemic control in patients with type 2 diabetes. HUMAN EXPOSURE AND TOXICITY: Sitagliptin improves glycemic control and is generally well-tolerated in patients with type 2 diabetes. Sitagliptin use has been associated with an increased risk of heart failure -related hospitalizations among patients with type 2 diabetes with pre-existing heart failure. More recently a study has pointed to the possible use of sitagliptin in the treatment of some neurodegenerative conditions of the peripheral nervous system. Sitagliptin appears to be free from the adverse effects of weight gain and hypoglycemia that are associated some other treatments. ANIMAL STUDIES: Renal and liver toxicity were observed in rodents at systemic exposure to sitagliptin at values 58 times the human exposure level. Transient treatment-related physical signs, some of which suggest neural toxicity, such as open-mouth breathing, salivation, white foamy emesis, ataxia, trembling, decreased activity, and/or hunched posture were observed in dogs at exposure levels approximately 23 times the clinical exposure level. Carcinogenicity studies in mice did not show an increased incidence of tumors in any organ up to 500 mg/kg, but in rats there was an increased incidence of combined liver adenoma/carcinoma in males and females and of liver carcinoma in females at 500 mg/kg. Reproductive effects in rats and rabbits were only seen at doses greater than 250 mg/kg. Incisor teeth abnormalities were observed in rats at exposure levels 67 times the clinical exposure level. Sitagliptin was not mutagenic or clastogenic with or without metabolic activation in the Ames bacterial mutagenicity assay, a Chinese hamster ovary (CHO) chromosome aberration assay, an in vitro cytogenetics assay in CHO cells, an in vitro rat hepatocyte DNA alkaline elution assay, and an in vivo micronucleus assay.
Hepatotoxicity
Liver injury due to sitagliptin is rare. In large clinical trials, serum enzyme elevations were no more common with sitagliptin therapy (0.5%) than with placebo (0.4%), and no instances of clinically apparent liver injury were reported. Since licensure, instances of serum enzyme elevations attributed to sitagliptin have been reported to the FDA and the sponsor. A single case report of clinically apparent liver injury has been published, but in a patient who also had hepatitis C. The pattern of serum enzyme elevations was hepatocellular and peak serum bilirubin was 9.4 mg/dL, with a rapid recovery upon stopping sitagliptin. Immunoallergic features and autoantibodies were absent.
Likelihood score: D (possible rare cause of clinically apparent liver injury).
Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the clinical use of sitagliptin during breastfeeding. Sitagliptin has a shorter half-life than most other dipeptidyl-peptidase IV inhibitors, so it might be a better choice among drugs in this class for nursing mothers. Monitoring of the breastfed infant's blood glucose is advisable during maternal therapy with sitagliptin. However, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.
Protein Binding
38%.
Interactions
Concomitant administration of cyclosporine and sitagliptin may increase absorption and plasma concentrations of sitagliptin. However, this interaction is not considered clinically important.
Sitagliptin and metformin have a potential additive effect on active glucagon-like peptide (GLP-1) concentrations. Pharmacokinetic interactions are unlikely. The relevance of these effects to glycemic control in patients with type 2 diabetes mellitus is unclear.
There was a slight increase in the area under the curve (AUC, 11%) and mean peak drug concentration (Cmax, 18%) of digoxin with the co-administration of 100 mg sitagliptin for 10 days. Patients receiving digoxin should be monitored appropriately. No dosage adjustment of digoxin or Januvia is recommended.
When sitagliptin was used in combination with a sulfonylurea or insulin, the incidence of hypoglycemia was greater than that in patients receiving placebo with a sulfonylurea or insulin. In a long-term (52-week) clinical noninferiority study, rates of hypoglycemia with sitagliptin/metformin combination therapy were lower than those observed with glipizide/metformin combination therapy. However, in a 24-week clinical study, rates of hypoglycemia in patients receiving sitagliptin and glimepiride with or without metformin were greater than those in patients receiving glimepiride and metformin. Patients receiving sitagliptin may require a lower dosage of a concomitant insulin secretagogue (e.g., sulfonylurea) or insulin to reduce the risk of hypoglycemia.
Non-Human Toxicity Values
LD50 Mouse oral 4000 mg/kg
LD50 Rat oral >3000 mg/kg
References

[1]. (R)-8-(3-amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylm ethyl)-3,7-dihydro-purine-2,6-dione (BI 1356), a novel xanthine-based dipeptidyl peptidase 4 inhibitor, has a superior potency and longer duration of acti.

[2]. Dipeptidyl peptidase IV inhibition with MK0431 improves islet graft survival in diabetic NOD mice partially via T-cell modulation. Diabetes, 2009. 58(3): p. 641-51.

[3]. Novel biological action of the dipeptidylpeptidase-IV inhibitor, sitagliptin, as a GLP-1 secretagogue. Endocrinology, 2012. 153(2): p. 564-73.

[4]. Inhibition of dipeptidyl peptidase IV with sitagliptin (MK0431) prolongs islet graft survival in streptozotocin-induced diabetic mice. Diabetes, 2008. 57(5): p. 1331-9.

[5]. Disposition of the dipeptidyl peptidase 4 inhibitor sitagliptin in rats and dogs. Drug Metab Dispos, 2007. 35(4): p. 525-32.

Additional Infomation
Therapeutic Uses
Hypoglycemic Agents
Januvia is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. /Included in US product label/
Januvia should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings.
Type 2 diabetes mellitus is a common chronic disease that causes significant morbidity and mortality worldwide. The primary goal of treatment is to target glycemic control by maintaining the glycosylated hemoglobin level near 6-7% without predisposing patients to hypoglycemia. Diabetes results from a combination of increased hepatic glucose production, decreased insulin secretion from beta cells, and insulin resistance in the peripheral tissues. Currently available antidiabetic agents work by different mechanisms to lower blood glucose levels. Unfortunately, each of them has its tolerability and safety concerns that limit its use and dose titration. Sitagliptin is the first antidiabetic agent from the class of dipeptidyl peptidase-4 enzyme inhibitors. It increases the amount of circulating incretins, which stimulate insulin secretion and inhibit glucose production. Sitagliptin was approved by the US Food and Drug Administration (FDA) for use with diet and exercise to improve glycemic control in adult patients with type 2 diabetes. It can be used alone or in combination with metformin or a thiazolidinedione (pioglitazone or rosiglitazone) when treatment with either drug alone provides inadequate glucose control. The usual adult dose is 100 mg once daily. A dose of 25-50 mg once daily is recommended for patients with moderate-to-severe renal impairment. In randomized, placebo-controlled trials that lasted for up to 6 months, sitagliptin lowered glycosylated hemoglobin levels by 0.5-0.8%. In a 52-week clinical trial, sitagliptin was shown to be noninferior to glipizide as an add-on agent in patients inadequately controlled on metformin alone. Sitagliptin was well tolerated with the most common side effects being gastrointestinal complaints (up to 16%), including abdominal pain, nausea and diarrhea; hypoglycemia and body weight gain occurred at similar rates compared with placebo. Overall, sitagliptin provides a treatment option for patients with type 2 diabetes as a monotherapy, or as an adjunct to metformin or a thiazolidinedione when patients achieve inadequate glycemic control while on either of the agents. It is also an alternative therapy for those patients who have contraindications or intolerability to other antidiabetic agents.
For more Therapeutic Uses (Complete) data for SITAGLIPTIN (6 total), please visit the HSDB record page.
Drug Warnings
/BOXED WARNING/ WARNING: LACTIC ACIDOSIS. Lactic acidosis is a rare, but serious, complication that can occur due to metformin accumulation. The risk increases with conditions such as sepsis, dehydration, excess alcohol intake, hepatic impairment, renal impairment, and acute congestive heart failure. The onset of lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. Laboratory abnormalities include low pH, increased anion gap, and elevated blood lactate. If acidosis is suspected, Janumet should be discontinued and the patient hospitalized immediately. /Sitagliptin and metformin hydrochloride combination product/
FDA is evaluating unpublished new findings by a group of academic researchers that suggest an increased risk of pancreatitis and pre-cancerous cellular changes called pancreatic duct metaplasia in patients with type 2 diabetes treated with a class of drugs called incretin mimetics. These findings were based on examination of a small number of pancreatic tissue specimens taken from patients after they died from unspecified causes. FDA has asked the researchers to provide the methodology used to collect and study these specimens and to provide the tissue samples so the Agency can further investigate potential pancreatic toxicity associated with the incretin mimetics. Drugs in the incretin mimetic class include exenatide (Byetta, Bydureon), liraglutide (Victoza), sitagliptin (Januvia, Janumet, Janumet XR, Juvisync), saxagliptin (Onglyza, Kombiglyze XR), alogliptin (Nesina, Kazano, Oseni), and linagliptin (Tradjenta, Jentadueto). These drugs work by mimicking the incretin hormones that the body usually produces naturally to stimulate the release of insulin in response to a meal. They are used along with diet and exercise to lower blood sugar in adults with type 2 diabetes. FDA has not reached any new conclusions about safety risks with incretin mimetic drugs. This early communication is intended only to inform the public and health care professionals that the Agency intends to obtain and evaluate this new information. ... FDA will communicate its final conclusions and recommendations when its review is complete or when the Agency has additional information to report. The Warnings and Precautions section of drug labels and patient Medication Guides for incretin mimetics contain warnings about the risk of acute pancreatitis. FDA has not previously communicated about the potential risk of pre-cancerous findings of the pancreas with incretin mimetics. FDA has not concluded these drugs may cause or contribute to the development of pancreatic cancer. At this time, patients should continue to take their medicine as directed until they talk to their health care professional, and health care professionals should continue to follow the prescribing recommendations in the drug labels. ...
Acute pancreatitis, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis, has been reported during postmarketing experience in patients receiving sitagliptin or sitagliptin/metformin. The most common manifestations associated with pancreatitis were abdominal pain, nausea, and vomiting. Hospitalization was required in 66% of 88 reported cases, including 2 cases of hemorrhagic or necrotizing pancreatitis that necessitated prolonged hospitalization and intensive-care unit (ICU) care. Pancreatitis occurred within 30 days of initiation of sitagliptin or sitagliptin/metformin therapy in 21% of cases; discontinuance of the drug led to resolution of pancreatitis in 53% of patients. At least one other risk factor (e.g., obesity, high cholesterol and/or triglyceride concentrations) was noted in 51% of cases.
Renal function should be assessed prior to initiation of sitagliptin and periodically thereafter. Worsening of renal function, including acute renal failure that sometimes required dialysis, has been reported in some patients during postmarketing experience. A subset of these patients had renal insufficiency, some of whom were prescribed inappropriate dosages of sitagliptin. A return to baseline levels of renal insufficiency has been observed with supportive treatment and discontinuance of potentially causative agents. Cautious reinitiation of sitagliptin can be considered if another etiology is deemed likely to have precipitated the acute worsening of renal function. The manufacturer states that sitagliptin has not been found to be nephrotoxic in clinical trials or in preclinical studies at clinically relevant dosages.
For more Drug Warnings (Complete) data for SITAGLIPTIN (17 total), please visit the HSDB record page.
Pharmacodynamics
Sitagliptin inhibits DPP-4 which leads to increased levels of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide(GIP), decreased levels of glucagon, and a stronger insulin response to glucose.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C16H15F6N5O
Molecular Weight
407.32
Exact Mass
407.118
Elemental Analysis
C, 47.18; H, 3.71; F, 27.99; N, 17.19; O, 3.93
CAS #
486460-32-6
Related CAS #
Sitagliptin phosphate;654671-78-0;Sitagliptin phosphate monohydrate;654671-77-9;(S)-Sitagliptin phosphate;823817-58-9;(Rac)-Sitagliptin;823817-56-7;Sitagliptin-d4 hydrochloride
PubChem CID
4369359
Appearance
White to off-white solid powder
Density
1.6±0.1 g/cm3
Boiling Point
529.9±60.0 °C at 760 mmHg
Flash Point
274.3±32.9 °C
Vapour Pressure
0.0±1.4 mmHg at 25°C
Index of Refraction
1.590
LogP
1.3
Hydrogen Bond Donor Count
1
Hydrogen Bond Acceptor Count
10
Rotatable Bond Count
4
Heavy Atom Count
28
Complexity
566
Defined Atom Stereocenter Count
1
SMILES
FC(C1=NN=C2C([H])([H])N(C(C([H])([H])[C@@]([H])(C([H])([H])C3=C([H])C(=C(C([H])=C3F)F)F)N([H])[H])=O)C([H])([H])C([H])([H])N21)(F)F
InChi Key
MFFMDFFZMYYVKS-SECBINFHSA-N
InChi Code
InChI=1S/C16H15F6N5O/c17-10-6-12(19)11(18)4-8(10)3-9(23)5-14(28)26-1-2-27-13(7-26)24-25-15(27)16(20,21)22/h4,6,9H,1-3,5,7,23H2/t9-/m1/s1
Chemical Name
(3R)-3-amino-1-[3-(trifluoromethyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one
Synonyms
EC 690-730-1; HSDB 7516; HSDB7516; HSDB-7516; Januvia; LEZ 763; LEZ-763; LEZ763; Tesavel; Xelevia; (R)-3-AMINO-1-(3-(TRIFLUOROMETHYL)-5,6-DIHYDRO-[1,2,4]TRIAZOLO[4,3-A]PYRAZIN-7(8H)-YL)-4-(2,4,5-TRIFLUOROPHENYL)BUTAN-1-ONE; sitagliptina; MK-0431; MK0431; MK 0431; MK-431; MK431; MK 431; Sitagliptin Phosphate; Sitagliptin Phosphate Monohydrate; trade name: Januvia Xelevia Janumet
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: >50 mg/mL
Water: N/A
Ethanol: N/A
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.14 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: ≥ 2.5 mg/mL (6.14 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 3: 2.5 mg/mL (6.14 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; Need heat to 60°C.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.


 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.4551 mL 12.2754 mL 24.5507 mL
5 mM 0.4910 mL 2.4551 mL 4.9101 mL
10 mM 0.2455 mL 1.2275 mL 2.4551 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

  • Calculate the Mass of a compound required to prepare a solution of known volume and concentration
  • Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
  • Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume
An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
  • Enter 5 in the Volume box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
  • Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
  • Enter 25 into the Concentration (End) box and select the correct unit (mM)
  • Enter 25 into the Volume (End) box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
  • To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
/

Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

  • Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
  • Click the “Calculate” button
  • The answer appears in the Volume (to add to vial) box
In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

Clinical Trial Information
Study to Evaluate the Efficacy and Safety of DA-1241 in Subjects With Presumed NASH
CTID: NCT06054815
Phase: Phase 2    Status: Completed
Date: 2024-11-14
Emulation of the SOUL Diabetes Trial in Healthcare Claims
CTID: NCT06659718
Phase:    Status: Active, not recruiting
Date: 2024-11-01
Comparative Effectiveness of Two Initial Combination Therapies in Patients With Recent Onset Diabetes
CTID: NCT06246799
Phase: Phase 3    Status: Not yet recruiting
Date: 2024-10-09
A Research Study Comparing a New Medicine Oral Semaglutide to Sitagliptin in People With Type 2 Diabetes
CTID: NCT04017832
Phase: Phase 3    Status: Completed
Date: 2024-10-01
Sitagliptin or BeiDouGen Capsule Improve the Pregnancy Outcome in Patients with PCOS
CTID: NCT06587698
Phase: N/A    Status: Recruiting
Date: 2024-09-19
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Anti-Diabetic Medications to Fight PD and LBD
CTID: NCT06263673
Phase: Phase 4    Status: Recruiting
Date: 2024-08-15


Effects of Sitagliptin in Individuals With Genetically Decreased DPP4
CTID: NCT04323189
Phase: Phase 4    Status: Recruiting
Date: 2024-07-29
Doxycycline in Type II Diabetes
CTID: NCT06329882
Phase: Phase 1/Phase 2    Status: Recruiting
Date: 2024-07-16
Effects of SGLT2i on the Cognitive Function in T2DM Patient (ESCDP)
CTID: NCT04304261
Phase: Phase 3    Status: Completed
Date: 2024-05-30
High-Dose Post-Transplant Cyclophosphamide, Bortezomib, and Sitagliptin for the Prevention of GVHD
CTID: NCT05895201
Phase: Phase 1/Phase 2    Status: Withdrawn
Date: 2024-04-29
Oral Hypoglycemic Therapy for Monogenic Variant Carriers of the Joslin Medalist Study
CTID: NCT04409795
Phase: Phase 2/Phase 3    Status: Enrolling by invitation
Date: 2024-03-08
Mechanism(s) Underlying Hypotensive Response to ARB/NEP Inhibition - Aim 1
CTID: NCT03738878
Phase: Phase 4    Status: Active, not recruiting
Date: 2024-03-05
A Clinical Trial to Evaluate the Food Effect on Pharmacokinetic Profiles and Safety of CKD-379
CTID: NCT06204107
Phase: Phase 1    Status: Completed
Date: 2024-01-12
Efficay and Safety of Empagliflozin Versus Sitagliptin for the In-patient Management of Hyperglycemia
CTID: NCT06187285
Phase: N/A    Status: Recruiting
Date: 2024-01-05
HbA1c Variability in Type II Diabetes
CTID: NCT02879409
Phase: N/A    Status: Active, not recruiting
Date: 2023-12-14
To Compare the Safety and Efficacy of Dapagliflozin Plus Metformin Versus Sitagliptin Plus Metformin for Treatment of Diabetes in Patients With Compensated and Stable Decompensated Cirrhosis
CTID: NCT06147518
Phase: N/A    Status: Not yet recruiting
Date: 2023-12-08
Effect of Dapagliflozin vs Sitagliptin on Liver Fat Accumulation and Body Composition in Patients With Diabetes Mellitus and Liver Transplantation
CTID: NCT05042505
Phase: N/A    Status: Recruiting
Date: 2023-10-19
SITAgliptin Plus GLARgine to Glycemic Control in the Hospital Setting (SITAGLAR-H)
CTID: NCT05579119
Phase: Phase 4    Status: Completed
Date: 2023-09-26
Using Sitagliptin as a Treatment to Prevent New Onset Diabetes After Kidney Transplantation
CTID: NCT00936663
Phase: Phase 4    Status: Terminated
Date: 2023-09-13
Perioperative Sitagliptin Medication for Reduction of the Inflammatory Response Associated With Cardiopulmonary Bypass
CTID: NCT05725798
Phase:    Status: Completed
Date: 2023-08-22
Effect of Sitagliptin on Polycystic Ovarian Syndrome Patients
CTID: NCT05972928
Phase: Phase 2/Phase 3    Status: Not yet recruiting
Date: 2023-08-02
Sitagliptin for the Treatment of Type 2 Diabetes
CTID: NCT04495881
Phase: Phase 4    Status: Recruiting
Date: 2023-07-28
Replication of the DAPA-CKD (Chronic Kidney Disease) Trial in Healthcare Claims Data
CTID: NCT04882813
Phase:    Status: Completed
Date: 2023-07-28
Replication of the TECOS Diabetes Trial in Healthcare Claims
CTID: NCT03936062
Phase:    Status: Completed
Date: 2023-07-27
Replication of the GRADE Diabetes Trial in Healthcare Claims Data
CTID: NCT05099198
Phase:    Status: Completed
Date: 2023-07-27
Impact of Sitagliptin on Cardiovascular Exercise Performance in Type 2 Diabetes
CTID: NCT01951339
Phase: N/A    Status: Completed
Date: 2023-07-12
Effects of Sitagliptin in Relatives of T1D Patients
CTID: NCT05219409
Phase: Phase 2/Phase 3    Status: Not yet recruiting
Date: 2023-05-10
Sitagliptin for Prevention of aGVHD After Alternative Donor Transplantation
CTID: NCT05149365
Phase: Phase 3    Status: Recruiting
Date: 2023-03-30
Drug Interaction Study Between Dorzagliatin and Sitagliptin
CTID: NCT03790839
Phase: Phase 1    Status: Completed
Date: 2023-02-28
Sitagliptin in Combination With Beidougen Capsule for Type 2 Diabetes
CTID: NCT05667220
Phase: Phase 4    Status: Unknown status
Date: 2023-01-03
Efficacy Study of Sitagliptin to Prevent New-onset Diabetes After Kidney Transplant
CTID: NCT01928199
Phase: Phase 4    Status: Completed
Date: 2022-12-30
Semaglutide vs Sitagliptin
CTID: NCT05195944
Phase: Phase 4    Status: Unknown status
Date: 2022-11-08
Cardiovascular Effects of GLP-1 Receptor Activation
CTID: NCT03101930
Phase: Phase 4    Status: Completed
Date: 2022-10-18
Efficacy of Ipragliflozin Compared With Sitagliptin in Uncontrolled Type 2 Diabetes With Sulfonylurea and Metformin
CTID: NCT03076112
Phase: Phase 3    Status: Completed
Date: 2022-10-04
Study to Assess Safety & Efficacy of Sitagliptin as Initial Oral Therapy for Treatment of Type 2 Diabetes Mellitus in Pediatric Participants. (MK-0431-083)
CTID: NCT01485614
Phase: Phase 3    Status: Completed
Date: 2022-09-23
Sitagliptin Plus Granulocyte-colony Stimulating Factor in Acute Myocardial Infarction
CTID: NCT00650143
Phase: Phase 2/Phase 3    Status: Completed
Date: 2022-08-25
Non-alcoholic Fatty Liver Disease and Its Treatment
CTID: NCT05480007
Phase: N/A    Status: Completed
Date: 2022-07-29
Cognitive Protective Effect of Newer Antidiabetic Drugs
CTID: NCT05347459
Phase:    Status: Unknown status
Date: 2022-07-26
Efficacy and Safety of Oral Semaglutide Using a Flexible Dose Adjustment Based on Clinical Evaluation Versus Sitagliptin in Subjects With Type 2 Diabetes Mellitus.
CTID: NCT02849080
Phase: Phase 3    Status: Completed
Date: 2022-07-20
Efficacy and Long-term Safety of Oral Semaglutide Versus Sitagliptin in Subjects With Type 2 Diabetes
CTID: NCT02607865
Phase: Phase 3    Status: Completed
Date: 2022-07-20
Phase 1 Bioequivalence Study of Dapagliflozin/Sitagliptin FDC vs Loose Combination of Single Components
CTID: NCT05266404
Phase: Phase 1    Status: Completed
Date: 2022-07-05
Effect of Exenatide, Sitagliptin or Glimepiride on Functional ß -Cell Mass
CTID: NCT00775684
Phase: N/A    Status: Completed
Date: 2022-06-07
The Effect of Glimepiride Compared With Sitagliptin as an add-on Therapy to Metformin in Severe Insulin Deficiency Diabetes
CTID: NCT05386186
Phase: Phase 4    Status: Unknown status
Date: 2022-05-23
Which is Better to Start With DPP-4 Inhibitors or SGLT-2 Inhibitors in Egyptian Diabetic Patients?
CTID: NCT05359341
Phase: N/A    Status: Completed
Date: 2022-05-03
The Combination of Sitagliptin and Danazol as the Treatment of Steroid-resistant/Relapse Immune Thrombocytopenia
CTID: NCT05353673
Phase: Phase 2    Status: Unknown status
Date: 2022-04-29
Sitagliptin in Type I Diabetic Patients
CTID: NCT01741103
Phase: N/A    Status: Withdrawn
Date: 2022-03-24
Glucagon-like Peptide-1 Levels, Insulin Resistance and Insulin Sensitivity Index in Type 2 Diabetes Mellitus
CTID: NCT03659461
Phase: N/A    Status: Completed
Date: 2022-03-15
Effect of Chronic Incretin-based Therapy in Cystic Fibrosis
CTID: NCT01879228
Phase: N/A    Status: Completed
Date: 2022-03-08
Effect of Chronic ACE and DPP4 Inhibition on Blood Pressure
CTID: NCT02130687
Phase: N/A    Status: Completed
Date: 2022-03-02
Triple Combination Therapy in Type 2 Diabetic Patients Who Had Inadequate Glycemic Control With Combination Therapy
CTID: NCT02338921
Phase: Phase 4    Status: Completed
Date: 2022-01-04
Sitagliptin Cardiovascular Outcomes Study (MK-0431-082)
CTID: NCT00790205
Phase: Phase 3    Status: Completed
Date: 2021-11-23
Mechanistic Evaluation of Glucose-lowering Strategies in Patients With Heart Failure
CTID: NCT02917031
Phase: Phase 4    Status: Completed
Date: 2021-11-08
The Effect of Sitagliptin Treatment in COVID-19 Positive Diabetic Patients
CTID: NCT04365517
Phase: Phase 3    Status: Unknown status
Date: 2021-09-28
Effect of CPL-2009-0031 in the Treatment of Patients With Uncontrolled Type 2 Diabetes Mellitus
CTID: NCT04801199
Phase: Phase 3    Status: Completed
Date: 2021-08-17
Interaction of Bexagliflozin With Metformin, Glimepiride and Sitagliptin
CTID: NCT02956044
Phase: Phase 1    Status: Completed
Date: 2021-07-22
Safety and Efficacy of Bexagliflozin Compared to Sitagliptin as Add-on Therapy to Metformin in Type 2 Diabetes Subjects
CTID: NCT03115112
Phase: Phase 3    Status: Completed
Date: 2021-06-22
Safety and Efficacy of Antidiabetic Drugs in Recently Diagnosed Patients With Type 2 Diabetes
CTID: NCT04916093
Phase: Phase 4    Status: Completed
Date: 2021-06-07
Effect of Neprilysin on Glucagon-Like Peptide-1 in Patients With Type 2 Diabetes
CTID: NCT03893526
Phase: Phase 4    Status: Completed
Date: 2021-05-05
Metabolic Responses of Dapagliflozin vs Sitagliptin in T2DM Patients Inadequately Controlled With Insulin Therapy
CTID: NCT03959501
Phase: Phase 4    Status: Completed
Date: 2021-04-29
Comparing the Effect of Sitagliptin/Metformin and Metformin in PCOS Patients
CTID: NCT04268563
Phase: Phase 1/Phase 2    Status: Unknown status
Date: 2021-03-22
Efficacy and Safety of Semaglutide Once-weekly Versus Sitagliptin Once-daily as add-on to Metformin in Subjects With Type 2 Diabetes (SUSTAIN - CHINA MRCT)
CTID: NCT03061214
Phase: Phase 3    Status: Completed
Date: 2021-03-02
Sitagliptin and the Risk for Hypoglycaemia in Type 2 Diabetes Patients
CTID: NCT03359590
Phase: Phase 2    Status: Completed
Date: 2021-02-21
Beta-cell Function in Glucose Abnormalities and Acute Myocardial Infarction
CTID: NCT00627744
Phase: Phase 4    Status: Completed
Date: 2021-02-12
A Study to Evaluate the Safety, Tolerability, PK and PD of DA-1241 in Healthy Male Subjects and Subjects With T2DM
CTID: NCT03646721
Phase: Phase 1    Status: Completed
Date: 2021-02-11
Sitagliptin for the Treatment of Grade 3-4 and Refractory Acute Graft-versus-host Disease
CTID: NCT04448587
Phase: Phase 2    Status: Unknown status
Date: 2021-02-02
Sitagliptin for Prevention of Acute Graft Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation
CTID: NCT02683525
Phase: Phase 2    Status: Completed
Date: 2021-01-22
Efficacy and Long-Term Safety of Vildagliptin as Add-on Therapy to Metformin in Patients With Type 2 Diabetes
CTID: NCT00860288
Phase: Phase 2/Phase 3    Status: Completed
Date: 2020-12-29
Clinical Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LEZ763
CTID: NCT01619332
Phase: Phase 1/Phase 2    Status: Completed
Date: 2020-12-17
Safety and Tolerability of Vildagliptin Versus Sitagliptin in Patients With Type 2 Diabetes and Severe Renal Insufficiency
CTID: NCT00616811
Phase: Phase 3    Status: Completed
Date: 2020-12-17
Safety and Tolerability of Vildagliptin Versus Sitagliptin in Patients With Type 2 Diabetes and Severe Renal Insufficiency (28-week Extension Study)
CTID: NCT00770081
Phase: Phase 3    Status: Completed
Date: 2020-12-17
Efficacy of Metformin Versus Sitagliptin on Benign Thyroid Nodules in Type 2 Diabetes
CTID: NCT04298684
Phase: Phase 4    Status: Unknown status
Date: 2020-09-11
SNP Study of DPP-4 and GLP-1R in Chinese People (Including Diabetes Patients)
CTID: NCT03108521
Phase: Phase 4    Status: Completed
Date: 2020-07-30
Dipeptidyl Peptidase-4 Inhibition in Psoriasis Patients With Diabetes (DIP): A Randomized Clinical Trial.
CTID: NCT01991197
Phase: Phase 2    Status: Completed
Date: 2020-05-14
Sitagliptin Therapy and Kinetics of Inflammatory Markers
CTID: NCT02536248
Phase: Phase 3    Status: Completed
Date: 2020-05-13
The Effect of Dipeptidyl Peptidase 4 Inhibition on Growth Hormone Secretion in Women With Polycystic Ovarian Syndrome
CTID: NCT02122380
Phase: Phase 4    Status: Completed
Date: 2020-05-08
Response of Gut Microbiota in Type 2 Diabetes to Hypoglycemic Agents
CTID: NCT04287387
Phase: Phase 4    Status: Unknown status
Date: 2020-02-27
Effects of Liraglutide in Young Adults With Type 2 DIAbetes (LYDIA)
CTID: NCT02043054
Phase: Phase 3    Status: Completed
Date: 2020-01-30
Dose Response Finding Study of MK-0431/ONO-5435 in Japanese Subjects With Impaired Glucose Tolerance (MK-0431-105)
CTID: NCT01405911
Phase: Phase 2    Status: Completed
Date: 2020-01-18
Sitagliptin for Hyperglycemia in Patients With T2DM Undergoing Cardiac Surgery
CTID: NCT02556918
Phase: Phase 4    Status: Completed
Date: 2019-12-23
An Efficacy Study of Canagliflozin or Sitagliptin to Determine Glucose Variability in Mexican Participants With Type 2 Diabetes Mellitus Inadequately Controlled on Metformin
CTID: NCT03267576
Phase: Phase 4    Status: Completed
Date: 2019-11-29
Assessment of the Effects of a DPP-4 Inhibitor (Sitagliptin) Januvia on Immune Function in Healthy Individuals
CTID: NCT00813228
Phase: Phase 1    Status: Completed
Date: 2019-11-29
Study of Real-world Evidence With SGLT2i (Dapagliflozin) and DPP4i (Sitagliptin) in Type 2 Diabetes Patients in Spain
CTID: NCT04149067
Phase:    Status: Completed
Date: 2019-11-04
Treatment of Diabetes in Patients With Systolic Heart Failure
CTID: NCT02920918
Phase: Phase 4    Status: Completed
Date: 2019-10-29
Study of Chiglitazar Compare With Sitagliptin in Type 2 Diabetes Patients
CTID: NCT02173457
Phase: Phase 3    Status: Completed
Date: 2019-10-25
A Comparison of Two Treatment Strategies in Older Participants With Type 2 Diabetes Mellitus (T2DM)
CTID: NCT02072096
Phase: Phase 4    Status: Terminated
Date: 2019-10-09
A Study of LY2409021 in Participants With Type 2 Diabetes Mellitus
CTID: NCT02111096
Phase: Phase 2    Status: Terminated
Date: 2019-10-09
Drug Transporter Interaction Study PHENTRA_2015_KPUK
CTID: NCT02743260
Phase: Phase 4    Status: Completed
Date: 2019-09-10
Involvement of Dipeptidyl Peptidase-4 and Sodium-glucose Co-transporter-2 in Extrapancreatic Glucagon Secretion
CTID: NCT04061473
Phase: N/A    Status: Completed
Date: 2019-09-04
Omarigliptin (MK-3102) Clinical Trial - Placebo- and Sitagliptin-Controlled Monotherapy Study in Japanese Patients With Type 2 Diabetes Mellitus (MK-3102-020)
CTID: NCT01703221
Phase: Phase 3    Status: Completed
Date: 2019-08-28
Randomized Evaluation of Anagliptin Versus Sitagliptin On Low-density lipoproteiN Cholesterol in Diabetes Trial
CTID: NCT02330406
Phase: Phase 4    Status: Completed
Date: 2019-08-28
Empagliflozin Versus Sitagliptin Therapy for Improvement of Myocardial Perfusion Reserve in Diabetic Patients With Coronary Artery Disease
CTID: NCT03208465
Phase: Phase 4    Status: Completed
Date: 2019-08-07
Sitagliptin Effects on Arterial Vasculature and Inflammation in Obesity
CTID: NCT02576288
Phase: Phase 2    Status: Completed
Date: 2019-07-17
The Effects of Neprilysin on Glucagon-like Peptide-1
CTID: NCT03717688
Phase: Phase 4    Status: Completed
Date: 2019-07-08
Dietary Impacts on Glucose-lowering Effects of Sitagliptin in Type 2 Diabetes
CTID: NCT02312063
Phase: Phase 4    Status: Completed
Date: 2019-07-01
Efficacy and Safety of Semaglutide Once-weekly Versus Sitagliptin Once-daily as add-on to Metformin and/or TZD in Subjects With Type 2 Diabetes
CTID: NCT01930188
Phase: Phase 3    Status: Completed
Date: 2019-06-13
Study of Management of Pasireotide-induced Hyperglycemia in Adult Patients With Cushing's Disease or Acromegaly
CTID: NCT02060383
Phase: Phase 4    Status: Completed
Date: 2019-05-29
Effects of Glutamine on GLP-1 and Insulin Secretion in Man
CTID: NCT00673894
Phase: N/A    Status: Completed
Date: 2019-05-13
Ertugliflozin vs. Glimepiride in Type 2 Diabetes Mellitus (T2DM) Participants on Metformin (MK-8835-002)
CTID: NCT01999218
Phase: Phase 3    Status: Completed
Date: 2019-04-02
Metformin and Sitagliptin in Women With Previous Gestational Diabetes
CTID: NCT01336322
Phase: Phase 2    Status: Completed
Date: 2019-03-25
A Study of the Safety and Efficacy of Sitagliptin Addition During Metformin Up-titration (MK-0431-848)
CTID: NCT02791490
Phase: Phase 3    Status: Completed
Date: 2019-02-28
Risk of Nocturnal Hypoglycemia and Arrhythmias With Sitagliptin Versus Glimepiride in Patients With Type 2 Diabetes
CTID: NCT02373865
Phase: Phase 4    Status: Terminated
Date: 2019-02-27
Randomized Sitagliptin Withdrawal Study (MK-0431-845)
CTID: NCT02738879
Phase: Phase 3    Status: Completed
Date: 2019-02-25
12-Week Study of DS-8500a in Subjects With Type 2 Diabetes Mellitus on Metformin
CTID: NCT02647320
Phase: Phase 2    Status: Completed
Date: 2019-02-25
Sitagliptin and Glucagon Counterregulation
CTID: NCT02256189
Phase: Phase 4    Status: Completed
Date: 2019-02-20
A Phase 2 Study of DS-8500a in Japanese Subjects With Type 2 Diabetes Mellitus (T2DM)
CTID: NCT02628392
Phase: N/A    Status: Completed
Date: 2019-02-12
Multicenter Phase II of CD26 Using Sitagliptin for Engraftment After UBC Transplant
CTID: NCT01720264
Phase: Phase 2    Status: Completed
Date: 2019-01-08
Dipeptidyl Peptidase-4 Inhibitor (Sitagliptin) Therapy in the Inpatients With Type 2 Diabetes
CTID: NCT01378117
Phase: Phase 4    Status: Completed
Date: 2018-12-07
A Study to Assess the Addition of Sitagliptin to Metformin Compared With the Addition of Dapagliflozin to Metformin in Participants With Type 2 Diabetes Mellitus (T2DM) and Mild Renal Impairment Who Have Inadequate Glycemic Control on Metformin With or Without a Sulfonylurea (MK-0431-838)
CTID: NCT02532855
Phase: Phase 3    Status: Completed
Date: 2018-11-20
A Pilot Study to Evaluate the Safety of a 3 Weeks Sitagliptin Treatment in HCC Patients Undergoing Liver Resection
CTID: NCT02650427
Phase: Phase 1    Status: Completed
Date: 2018-10-18
Efficacy and Safety of Switching From Sitagliptin to Liraglutide in Subjects With Type 2 Diabetes Not Achieving Adequate Glycaemic Control on Sitagliptin and Metformin
CTID: NCT01907854
Phase: Phase 4    Status: Completed
Date: 2018-10-02
Study Of Safety And Efficacy Of Ertugliflozin (PF-04971729, MK-8835) In Participants With Type 2 Diabetes (MK-8835-016)
CTID: NCT01059825
Phase: Phase 2    Status: Completed
Date: 2018-09-13
Efficacy and Safety of Ertugliflozin (MK-8835/PF-04971729) With Sitagliptin in the Treatment of Participants With Type 2 Diabetes Mellitus (T2DM) With Inadequate Glycemic Control on Diet and Exercise (MK-8835-017)
CTID: NCT02226003
Phase: Phase 3    Status: Completed
Date: 2018-09-13
A Trial Comparing the Safety and Efficacy of Semaglutide Once Weekly Versus Sitagliptin Once Daily in Japanese Subjects With Type 2 Diabetes
CTID: NCT02254291
Phase: Phase 3    Status: Completed
Date: 2018-09-13
Safety and Efficacy of Ertugliflozin in the Treatment of Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin and Sitagliptin (MK-8835-006; VERTIS SITA2)
CTID: NCT02036515
Phase: Phase 3    Status: Completed
Date: 2018-09-13
Ertugliflozin and Sitagliptin Co-administration Factorial Study (VERTIS FACTORAL, MK-8835-005)
CTID: NCT02099110
Phase: Phase 3    Status: Completed
Date: 2018-09-12
Study to Evaluate the Safety and Efficacy of the Addition of Omarigliptin (MK-3102) Compared With the Addition of Sitagliptin in Participants With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin (MK-3102-026)
CTID: NCT01841697
Phase: Phase 3    Status: Completed
Date: 2018-09-10
Double-blind Ipragliflozin Add-on Study in Japanese Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Sitagliptin (MK-0431J-843)
CTID: NCT02577003
Phase: Phase 3    Status: Completed
Date: 2018-09-04
Ipragliflozin Add-on Long-term Study in Japanese Participants With Type 2 Diabetes Mellitus on Sitagliptin (MK-0431J-849)
CTID: NCT02564211
Phase: Phase 3    Status: Completed
Date: 2018-09-04
Double-blind Sitagliptin Add-on Study in Japanese Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Ipragliflozin (MK-0431J-842)
CTID: NCT02577016
Phase: Phase 3    Status: Completed
Date: 2018-08-31
Effect of DPP4 Inhibition on Vasoconstriction
CTID: NCT02639637
Phase: Phase 4    Status: Completed
Date: 2018-08-27
A Study of the Efficacy and Safety of MK-0431D (a Fixed-dose Combination of Sitagliptin and Simvastatin) for the Treatment of Participants With Type 2 Diabetes Mellitus (T2DM) With Inadequate Glycemic Control on Metformin Monotherapy (MK-0431D-266)
CTID: NCT01678820
Phase: Phase 3    Status: Terminated
Date: 2018-08-24
A Study of LY3325656 in Healthy Participants and Participants With Type 2 Diabetes
CTID: NCT03115099
Phase: Phase 1    Status: Completed
Date: 2018-08-23
Metformin Add-on Regimen Comparison Study in Japanese Participants With Type 2 Diabetes Mellitus (MK-0431A-136)
CTID: NCT01545388
Phase: Phase 3    Status: Completed
Date: 2018-08-22
Efficacy of Sitagliptin and Glibenclamide on the Glucose Variability in Japanese Participants With Type 2 Diabetes Mellitus (MK-0431-355)
CTID: NCT02318693
Phase: Phase 4    Status: Completed
Date: 2018-08-21
A Study of the Safety and Efficacy of Glimepiride, Gliclazide, Repaglinide or Acarbose When Added to Sitagliptin + Metformin Combination Therapy in Chinese Participants With Diabetes (MK-0431-313)
CTID: NCT01709305
Phase: Phase 4    Status: Completed
Date: 2018-08-21
Study of Sitagliptin for the Treatment of Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Insulin (MK-0431-260)
CTID: NCT01462266
Phase: Phase 3    Status: Completed
Date: 2018-08-17
A Study in China Evaluating the Safety and Efficacy of Adding Sitagliptin to Stable Therapy With Sulfonylurea With or Without Metformin in Participants With Type 2 Diabetes Mellitus (T2DM) (MK-0431-253)
CTID: NCT01590771
Phase: Phase 3    Status: Completed
Date: 2018-08-17
A Study in China Evaluating the Safety and Efficacy of Adding Sitagliptin to Stable Therapy With Insulin With or Without Metformin in Participants With Type 2 Diabetes Mellitus (T2DM) (MK-0431-254)
CTID: NCT01590797
Phase: Phase 3    Status: Completed
Date: 2018-08-17
Evogliptin in Type 2 Diabetes Mellitus (EVOLUTION: EVOgLiptina no Diabetes Mellitus TIpO 2)
CTID: NCT02689362
Phase: Phase 2    Status: Completed
Date: 2018-08-14
Protective Effects of Sitagliptin on β Cell Function in Patients With Adult-onset Latent Autoimmune Diabetes (LADA)
CTID: NCT01159847
Phase: Phase 1/Phase 2    Status: Completed
Date: 2018-07-31
Effects of a Dipeptidyl Peptidase-4 Inhibitor Sitagliptininsulin on the Progression of Coronary Atherosclerosis in Patients With Type 2 Diabetes
CTID: NCT03602638
Phase: Phase 4    Status: Unknown status
Date: 2018-07-27
A Study of the Co-administration of Sitagliptin and Atorvastatin in Inadequately Controlled Type 2 Diabetes Mellitus (MK-0431E-211)
CTID: NCT01477853
Phase: Phase 3    Status: Terminated
Date: 2018-07-26
Sitagliptin and Brown Adipose Tissue
CTID: NCT02294084
Phase: Phase 4    Status: Completed
Date: 2018-07-16
Sitagliptin Dose Determination Study
CTID: NCT01530178
Phase: Phase 4    Status: Completed
Date: 2018-07-16
Sitagliptin in Non-Diabetic Patients Undergoing General Surgery
CTID: NCT02741687
Phase: Phase 4    Status: Completed
Date: 2018-06-27
A Method to Evaluate Glucose-Dependent Insulin Secretion in Healthy Males (MK-0431-179)
CTID: NCT00888238
Phase: Phase 1    Status: Completed
Date: 2018-06-26
Prevention of Cystic Fibrosis Diabetes
CTID: NCT00967798
Phase: Phase 3    Status: Terminated
Date: 2018-06-25
Sitagliptin for Reducing Inflammation and Immune Activation
CTID: NCT02513771
Phase: Phase 2    Status: Completed
Date: 2018-06-18
Use of Sitagliptin for Stress Hyperglycemia or Mild Diabetes Following Cardiac Surgery
CTID: NCT01970462
Phase: Phase 4    Status: Terminated
Date: 2018-06-18
Study to Evaluate the Efficacy and Safety of Saxagliptin Co-administered With Dapagliflozin in Combination With Metformin Compared to Sitagliptin in Combination With Metformin in Adult Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Therapy Alone
CTID: NCT02284893
Phase: Phase 3    Status: Completed
Date: 2018-06-01
Effect of DPP4 Inhibition on Growth Hormone Secretion
CTID: NCT01701973
Phase: Phase 4    Status: Completed
Date: 2018-05-29
GLP-1 Signaling in Truncally Vagotomized Subjects
CTID: NCT02940184
Phase: N/A    Status: Unknown status
Date: 2018-05-22
Effectiveness of Sitagliptin for HIV Insulin Resistance and Inflammation
CTID: NCT01552694
Phase: Phase 3    Status: Completed
Date: 2018-05-08
Sitagliptin in Non-Diabetic Patients Undergoing Cardiac Surgery
CTID: NCT02443402
Phase: Phase 4    Status: Completed
Date: 2018-02-06
Effect of Sitagliptin on Progression of Coronary Intermediate Lesion
CTID: NCT02655757
Phase: Phase 4    Status: Completed
Date: 2018-01-25
Sitagliptin in the Elderly
CTID: NCT00451113
Phase: Phase 2    Status: Completed
Date: 2018-01-18
A Study in Type 2 Diabetics of Single and Multiple Doses of Orally Administered GSK1292263 to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics
CTID: NCT01119846
Phase: Phase 2    Status: Completed
Date: 2018-01-17
A Study to Investigate the Glucose Lowering Effects of Dextromethorphan Alone or in Combination With Sitagliptin in Subjects With Type 2 Diabetes Mellitus (T2DM) After an Oral Glucose Tolerance Test
CTID: NCT01936025
Phase: Phase 2    Status: Completed
Date: 2017-11-07
A Study Investigating Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK2330672 Administered With Metformin to Type 2 Diabetes Patients
CTID: NCT02202161
Phase: Phase 2    Status: Completed
Date: 2017-11-06
Effect of Sitagliptin on Graft Function Following Islet Transplantation
CTID: NCT00853944
Phase: Phase 3    Status: Terminated
Date: 2017-10-30
Response To Oral Agents in Diabetes (ROAD)- Pilot Study
CTID: NCT00780715
Phase: Phase 4    Status: Completed
Date: 2017-10-26
A Study in Type 2 Diabetic Subjects on Stable Metformin Therapy to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Co-administering Single and Multiple Oral Doses of GSK1292263
CTID: NCT01128621
Phase: Phase 2    Status: Completed
Date: 2017-10-16
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Biological Data
  • SITAGLIPTIN

    The effects of MK0431 in diabetic NOD mice after islet transplantation.Diabetes.2009 Mar;58(3):641-51.
  • SITAGLIPTIN

    MK0431 regulates the migration of CD4+ T-cells.Diabetes.2009 Mar;58(3):641-51.
  • SITAGLIPTIN

    Time-course monitoring of glucose responses, plasma chemistry, and islet graft survival after islet transplantation.Diabetes.2009 Mar;58(3):641-51.
  • SITAGLIPTIN

  • SITAGLIPTIN

  • SITAGLIPTIN

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