Sitagliptin drug class
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Sitagliptin Drug Class: Dipeptidyl Peptidase-4 (DPP-4) Inhibitors
Introduction to Sitagliptin and Its Mechanism of Action
Sitagliptin, marketed under various brand names such as Januvia, Glactiv, and Tesavel, is an oral antihyperglycemic agent used primarily for the treatment of type 2 diabetes mellitus. It belongs to the drug class known as dipeptidyl peptidase-4 (DPP-4) inhibitors 123. DPP-4 inhibitors work by enhancing the body's ability to regulate blood glucose levels. They achieve this by increasing the active levels of incretins, specifically glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), which in turn stimulate insulin release and inhibit glucagon secretion 346.
Clinical Efficacy and Glycemic Control
Sitagliptin has been extensively studied in clinical trials, demonstrating its efficacy in improving glycemic control. It has been shown to significantly reduce glycosylated hemoglobin (HbA1c) levels when used as monotherapy or in combination with other antihyperglycemic agents such as metformin, pioglitazone, sulfonylureas, and insulin 135. In comparative studies, sitagliptin was found to be noninferior to metformin and glipizide in terms of HbA1c reduction, and it generally did not differ significantly from rosiglitazone when used as an add-on treatment 1.
Pharmacokinetics and Pharmacodynamics
Sitagliptin is an orally active and highly selective DPP-4 inhibitor. It is well-absorbed, with an oral bioavailability of approximately 87%, and is primarily excreted unchanged in the urine 247. The drug exhibits a dose-dependent inhibition of plasma DPP-4 activity, leading to increased levels of active GLP-1 and improved glycemic control without causing significant hypoglycemia 47.
Safety and Tolerability
Sitagliptin is generally well-tolerated, with a safety profile comparable to placebo in clinical trials. It has a low risk of hypoglycemia, particularly when not used in combination with other agents that may cause hypoglycemia, such as sulfonylureas or insulin 135. Additionally, sitagliptin is weight-neutral, making it a favorable option for patients concerned about weight gain 135.
Potential Risks and Controversies
Despite its benefits, there have been concerns regarding the potential risk of pancreatitis and other pancreatic adverse events associated with DPP-4 inhibitors, including sitagliptin. However, current evidence and regulatory reviews have not established a causal relationship between sitagliptin and these adverse events 610. Long-term studies and postmarketing surveillance continue to monitor these potential risks.
Conclusion
Sitagliptin, as a member of the DPP-4 inhibitor class, offers a valuable treatment option for patients with type 2 diabetes. Its efficacy in improving glycemic control, favorable safety profile, and convenient oral administration make it a widely used antihyperglycemic agent. While ongoing research is necessary to fully understand its long-term safety, current evidence supports its use as both an initial and add-on therapy for managing type 2 diabetes 1356.
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Most relevant research papers on this topic
Sitagliptin
Sitagliptin is a well-tolerated and effective treatment option for type 2 diabetes, with oral administration, a generally weight-neutral effect, and low risk of hypoglycemia.
RCT
Highly CitedPharmacokinetics and pharmacodynamics of sitagliptin, an inhibitor of dipeptidyl peptidase IV, in healthy subjects: Results from two randomized, double‐blind, placebo‐controlled studies with single oral doses
Sitagliptin shows promising pharmacokinetics and pharmacodynamics in healthy subjects, with potential for treating type 2 diabetes.
RCTHighly CitedSitagliptin, a DPP-4 inhibitor for the treatment of patients with type 2 diabetes: a review of recent clinical trials
Sitagliptin is an effective and well-tolerated oral DPP-4 inhibitor for glycemic control in patients with type 2 diabetes, offering potential as initial therapy or add-on therapy.
Systematic ReviewHighly CitedPharmacokinetic and pharmacodynamic properties of multiple oral doses of sitagliptin, a dipeptidyl peptidase-IV inhibitor: a double-blind, randomized, placebo-controlled study in healthy male volunteers.
Multiple oral doses of sitagliptin show similar pharmacokinetic and pharmacodynamic properties and tolerability in healthy male volunteers with type 2 diabetes mellitus.
RCTHighly CitedSitagliptin, a DPP-4 inhibitor for the treatment of patients with type 2 diabetes: a review of recent clinical trials.
Sitagliptin is an effective and well-tolerated oral DPP-4 inhibitor for glycemic control in patients with type 2 diabetes, and may be considered for initial therapy or add-on therapy.
Systematic ReviewHighly CitedSitagliptin: A Review of Its Use in Patients with Type 2 Diabetes Mellitus
Sitagliptin is an effective and generally well-tolerated treatment option for patients with type 2 diabetes, improving glycemic control and reducing the risk of hypoglycemia.
Literature ReviewHighly CitedSitagliptin phosphate: a DPP-4 inhibitor for the treatment of type 2 diabetes mellitus.
Sitagliptin phosphate significantly reduces HbA(1c) levels in type 2 diabetes patients when used alone or in combination with metformin or pioglitazone, and is well-tolerated.
Systematic ReviewHighly CitedEfficacy of sitagliptin for the hospital management of general medicine and surgery patients with type 2 diabetes (Sita-Hospital): a multicentre, prospective, open-label, non-inferiority randomised trial.
Sitagliptin-basal insulin is as effective as a basal-bolus insulin regimen for managing type 2 diabetes in hospitalized patients, with similar duration of stay and blood glucose control.
RCTHighly CitedBiowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Sitagliptin phosphate monohydrate.
The BCS-based biowaiver can be implemented for solid immediate-release oral dosage forms containing sitagliptin phosphate monohydrate, as an alternative to pharmacokinetic studies in human volunteers, provided the test product is formulated solely with common excipients and meets all in vitro dissolution
Literature ReviewThe Biological Impacts of Sitagliptin on the Pancreas of a Rat Model of Type 2 Diabetes Mellitus: Drug Interactions with Metformin
Sitagliptin has a cytoprotective effect on beta-cell damage and does not show any detrimental effects on the exocrine pancreas in a rat model of type 2 diabetes mellitus.
RCT
Animal Study