Assessing the general safety and tolerability of vildagliptin: value of pooled analyses from a large safety database versus evaluation of individual studies

• Published in: Vascular health and risk management 2011-01, Vol.7, p.49-57
• Main Authors: Schweizer, Anja, Dejager, Sylvie, Foley, James E, Kothny, Wolfgang
• Format: Article
• Language: English
• Subjects: Adamantane - adverse effects; Adamantane - analogs & derivatives; Adamantane - therapeutic use; Clinical trials; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Consumer Product Safety; Databases, Factual; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; dipeptidyl peptidase-4; Dipeptidyl-Peptidase IV Inhibitors - adverse effects; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use; Edema; Evidence-Based Medicine; Humans; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; Nitriles - adverse effects; Nitriles - therapeutic use; Odds Ratio; Original Research; Pyrrolidines - adverse effects; Pyrrolidines - therapeutic use; Risk Assessment; Risk Factors; safety; Time Factors; Treatment Outcome; type 2 diabetes; Vildagliptin
• ISSN: 1178-2048; 1176-6344; 1178-2048
• DOI: 10.2147/VHRM.S16925

Analyzing safety aspects of a drug from individual studies can lead to difficult-to-interpret results. The aim of this paper is therefore to assess the general safety and tolerability, including incidences of the most common adverse events (AEs), of vildagliptin based on a large pooled database of Phase II and III clinical trials. Safety data were pooled from 38 studies of ≥ 12 to ≥ 104 weeks' duration. AE profiles of vildagliptin (50 mg bid; N = 6116) were evaluated relative to a pool of comparators (placebo and active comparators; N = 6210). Absolute incidence rates were calculated for all AEs, serious AEs (SAEs), discontinuations due to AEs, and deaths. Overall AEs, SAEs, discontinuations due to AEs, and deaths were all reported with a similar frequency in patients receiving vildagliptin (69.1%, 8.9%, 5.7%, and 0.4%, respectively) and patients receiving comparators (69.0%, 9.0%, 6.4%, and 0.4%, respectively), whereas drug-related AEs were seen with a lower frequency in vildagliptin-treated patients (15.7% vs 21.7% with comparators). The incidences of the most commonly reported specific AEs were also similar between vildagliptin and comparators, except for increased incidences of hypoglycemia, tremor, and hyperhidrosis in the comparator group related to the use of sulfonylureas. The present pooled analysis shows that vildagliptin was overall well tolerated in clinical trials of up to >2 years in duration. The data further emphasize the value of a pooled analysis from a large safety database versus assessing safety and tolerability from individual studies.