Safety and tolerability of sitagliptin in clinical studies: a pooled analysis of data from 10,246 patients with type 2 diabetes

Abstract

BackgroundIn a previous pooled analysis of 12 double-blind clinical studies that included data on 6,139 patients with type 2 diabetes, treatment with sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, was shown to be generally well tolerated compared with treatment with control agents. As clinical development of sitagliptin continues, additional studies have been completed, and more patients have been exposed to sitagliptin. The purpose of the present analysis is to update the safety and tolerability assessment of sitagliptin by pooling data from 19 double-blind clinical studies.MethodsThe present analysis included data from 10,246 patients with type 2 diabetes who received either sitagliptin 100 mg/day (N = 5,429; sitagliptin group) or a comparator agent (placebo or an active comparator) (N = 4,817; non-exposed group). The 19 studies from which this pooled population was drawn represent the double-blind, randomized studies that included patients treated with the usual clinical dose of sitagliptin (100 mg/day) for between 12 weeks and 2 years and for which results were available as of July 2009. These 19 studies assessed sitagliptin taken as monotherapy, initial combination therapy with metformin or pioglitazone, or as add-on combination therapy with other antihyperglycemic agents (metformin, pioglitazone, a sulfonylurea ± metformin, insulin ± metformin, or rosiglitazone + metformin). Patients in the non-exposed group were taking placebo, metformin, pioglitazone, a sulfonylurea ± metformin, insulin ± metformin, or rosiglitazone + metformin. The analysis used patient-level data from each study to evaluate between-group differences in the exposure-adjusted incidence rates of adverse events.ResultsSummary measures of overall adverse events were similar in the sitagliptin and non-exposed groups, except for an increased incidence of drug-related adverse events in the non-exposed group. Incidence rates of specific adverse events were also generally similar between the two groups, except for increased incidence rates of hypoglycemia, related to the greater use of a sulfonylurea, and diarrhea, related to the greater use of metformin, in the non-exposed group and constipation in the sitagliptin group. Treatment with sitagliptin was not associated with an increased risk of major adverse cardiovascular events.ConclusionsIn this updated pooled safety analysis of data from 10,246 patients with type 2 diabetes, sitagliptin 100 mg/day was generally well tolerated in clinical trials of up to 2 years in duration.

A Physiologic and Pharmacological Basis for Implementation of Incretin Hormones in the Treatment of Type 2 Diabetes Mellitus

“…41 However, a recent safety meta-analysis evaluated the general safety and tolerability profile of sitagliptin from more than 10,000 patients with type 2 DM. 53 The incidence of infections was no different than with comparators. There were no between-group differences using the terms nasopharyngitis, bronchitis, and urinary tract infection.…”

“…There were no between-group differences using the terms nasopharyngitis, bronchitis, and urinary tract infection. 53 Bruce et al 51 recently reported the results of a metaanalysis to evaluate the safety and tolerability of exenatide and included 11 comparator-controlled clinical trials. Data from 2251 exenatide-treated patients and 1603 comparator-treated patients were reviewed.…”

Sitagliptin counteracts seasonal fluctuation of glycemic control

“…Further investigations are needed to confirm whether better glycemic control by using sitagliptin with or without other oral hypoglycemic agents can improve pre-existing atheroma and thus prevent major cardiovascular events [19][20][21][22][23][24][25][26] .…”

An Inhibitory Antibody against Dipeptidyl Peptidase IV Improves Glucose Tolerance in Vivo

“…They are linagliptin, sitagliptin, vildagliptin, saxagliptin, and alogliptin (13,20,21). In humans, the approved compounds are generally well tolerated and demonstrate various degrees of efficacy in treating type 2 diabetes at recommended doses, sug-gesting that inhibition of DPP-IV activity represents a desirable therapeutic approach for type 2 diabetes (13,(22)(23)(24)(25). However, adverse effects such as nausea, common cold-like symptoms, and pancreatitis have been reported for approved DPP-IV inhibitors (25).…”

“…In humans, the approved compounds are generally well tolerated and demonstrate various degrees of efficacy in treating type 2 diabetes at recommended doses, sug-gesting that inhibition of DPP-IV activity represents a desirable therapeutic approach for type 2 diabetes (13,(22)(23)(24)(25). However, adverse effects such as nausea, common cold-like symptoms, and pancreatitis have been reported for approved DPP-IV inhibitors (25). Most of the small molecules are competitive reversible inhibitors with different degrees of selectivity toward other family members of prolyl peptidases such as DPP-VIII and DPP-IX.…”