Safety and Tolerability of Sitagliptin in Type 2 Diabetes: Pooled Analysis of 25 Clinical Studies

Abstract

IntroductionIn a previous pooled analysis of 19 double-blind clinical studies conducted by Merck, which included data available as of July 2009 on 10,246 patients with type 2 diabetes (T2DM), treatment with sitagliptin was shown to be generally well tolerated compared with treatment with control agents. As the sitagliptin clinical development program continues, additional studies with sitagliptin have been completed. The present analysis updates the safety and tolerability assessment of sitagliptin by examining pooled data from 25 double-blind clinical studies.MethodsThe present analysis included data from 14,611 patients in 25 studies with T2DM who received either sitagliptin 100 mg/day (n = 7,726; sitagliptin group) or a comparator agent (n = 6,885; non-exposed group). These studies represent all randomized, double-blind trials conducted by Merck 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 December 2011. These studies assessed sitagliptin, versus comparator agents, 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 metformin + pioglitazone or rosiglitazone). Patient-level data from each study were used to evaluate between-group differences in the exposure-adjusted incidence rates of adverse events (AEs).ResultsOverall incidence rates of AEs and drug-related AEs were higher in the non-exposed group compared with the sitagliptin group. Incidence rates of specific AEs were generally similar between the two groups, except for higher 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 of constipation in the sitagliptin group. Treatment with sitagliptin was not associated with an increased risk of major adverse cardiovascular events, malignancy, or pancreatitis.ConclusionIn this updated pooled safety analysis of data from 14,611 patients with T2DM, sitagliptin 100 mg/day was generally well tolerated in clinical trials of up to 2 years in duration.

A randomized clinical trial of the efficacy and safety of sitagliptin compared with dapagliflozin in patients with type 2 diabetes mellitus and mild renal insufficiency: The CompoSIT‐R study

“…When the background medication included a sulfonylurea, the rates of hypoglycaemia were higher and similar in both groups, as expected due to the influence of this class of agent 14, 15, 16. With regard to the small increase in the observed incidences of abdominal pain and vomiting with sitagliptin compared with dapagliflozin, and of edema peripheral with dapagliflozin compared with sitagliptin, imbalances of this type have not previously been noted in pooled safety analyses of either treatment 17, 18…”

Efficacy and Safety of Saxagliptin in Older Participants in the SAVOR-TIMI 53 Trial

“…Two meta-analyses suggested that the DPP-4 inhibitors are associated with reduced CV risk (23,24). Importantly, however, these data were obtained predominantly from relatively small and/or short-term investigations (18,19,30), systematic reviews (21,28,29), and pooled analyses (20,22,(25)(26)(27)31,32) in by-and-large younger and healthier study participants with very limited, and generally unadjudicated, CV safety information.…”

Impaired expression of sex hormone receptors in male reproductive organs of diabetic rat in response to oral antidiabetic drugs

“…Since that date the use of dipeptidyl peptidase-4 (DPP-4) inhibitors for the management of type 2 diabetic patients has increased. Continued assessment of adverse events of sitagliptin reported from clinical trials and post--marketing environment is ongoing [14]. Pioglitazone (a thiazolidinedione) acts as an insulin sensitizer and is used for treating type 2 diabetes [15].…”