Pioglitazone utilization, efficacy & safety in Indian type 2 diabetic patients

Abstract

Background & objectives:With pioglitazone ban and subsequent revoking in India along with varying regulatory decisions in other countries, it was decided to carry out a systematic review on its safety, efficacy and drug utilization in patients with type 2 diabetes mellitus (T2DM) in India and compare with the data from the European Medicines Agency Assessment Report (EMA-AR).Methods:Systematic review was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching Medline/PubMed, Google Scholar and Science Direct databases using ‘pioglitazone AND India AND human’ and ‘pioglitazone AND India AND human AND patient’ and compared with EMA-AR. Spontaneous reports in World Health Organization VigiBase from India were compared with VigiBase data from other countries.Results:Sixty six publications, 26 (efficacy), 32 (drug utilization) and eight (safety), were retrieved. In India, pioglitazone was used at 15-30 mg/day mostly with metformin and sulphonylurea, being prescribed to 26.7 and 8.4 per cent patients in north and south, respectively. The efficacy in clinical trials (CTs) was similar to those in EMA-AR. Incidence of bladder cancer in pioglitazone exposed and non-exposed patients was not significantly different in an Indian retrospective cohort study. There were two cases and a series of eight cases of bladder cancer published but none reported in VigiBase.Interpretation & conclusions:In India, probably due to lower dose, lower background incidence of bladder cancer and smaller sample size in epidemiological studies, association of bladder cancer with pioglitazone was not found to be significant. Reporting of CTs and adverse drug reactions to Clinical Trials Registry of India and Pharmacovigilance Programme of India, respectively, along with compliance studies with warning given in package insert and epidemiological studies with larger sample size are needed.

Post-marketing safety signals

“…Reports about an increased risk of pioglitazone led to its withdrawal from the French market 3 . The USFDA did not suspend the market authorization but added a black box warning for bladder cancer risks 3 .…”

“…Reports about an increased risk of pioglitazone led to its withdrawal from the French market 3 . The USFDA did not suspend the market authorization but added a black box warning for bladder cancer risks 3 . Indian drug regulatory authorities withdrew pioglitazone in June 2013 3 but then revoked the ban 3 due to lack of sufficient evidence and recommendation by the Drug Technical Advisory Board.…”

“…In view of such regulatory decisions, Pai and Kshirsagar 3 carried out a systematic review of publications on pioglitazone safety, efficacy and drug utilization in patients with type 2 diabetes in India and compared it with the data from European Medicines Agency Assessment Report (EMA-AR). No cases of bladder cancer were reported from India in VigiBase (WHO global database of individual case safety reports submitted by member countries) though there were eight cases reported in literature.…”

“…No cases of bladder cancer were reported from India in VigiBase (WHO global database of individual case safety reports submitted by member countries) though there were eight cases reported in literature. The information from published literature suggested that pioglitazone was used in lower than recommended dose, mostly with metformin and sulfonylurea 3 . There was regional variation also.…”

“…There was regional variation also. Pioglitazone was prescribed to 26.7 per cent patients in north and 8.4 per cent patients in the southern region in India 3 . The efficacy in clinical trials was similar to EMA-AR.…”