A SECONDARY ANALYSIS OF CONCURRENT USE OF METFORMIN AND TOLVAPTAN IN ADPKD TOLVAPTAN TRIALS
Isabelle Kitty Stanley1, Anton Palma2, Andrea Viecelli1,3, David Johnson1,3, Carmel Hawley1,3, Christine Staatz4, Andrew Mallett1,5 1The University Of Queensland, Faculty of Medicine, Brisbane, Queensland, Australia2Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, New Jersey, USA3Department of Kidney and Transplant Services, Brisbane, Queensland, Australia4The University of Queensland, School of Pharmacy, Brisbane, Queensland, Australia5Townsville Institute of Health Research and Innovation, Townsville, Queensland, Australia
Abstract
Aim: We aimed to assess the safety and efficacy of concurrent use of metformin with tolvaptan, through post-hoc analysis of metformin treated participants in tolvaptan trials.
Background: Autosomal dominant polycystic kidney disease (ADPKD) currently only has one therapeutic agent that has demonstrated disease modifying benefit, tolvaptan. The anti-diabetic medication, metformin has been theorised to potential be beneficial; and has been found safe and tolerable in two phase II trials, with a non-significant slowing of eGFR decline and total kidney volume (TKV) expansion. Given the established role of tolvaptan and the potential role of metformin in the management of ADPKD, the safety and efficacy of combined therapy are also of interest.
Methods: Tolvaptan’s efficacy was established in two phase III trials: TEMPO 3:4 and REPRISE. We analysed pooled data from these trials to evaluate the safety and efficacy on eGFR and TKV change from baseline among participants prescribed metformin at baseline.
Results: Participants were classified into four distinct categories, tolvaptan only (n=1,390), placebo only (n=1,070), tolvaptan with metformin (n=18), and placebo with metformin (n=10). Participants receiving tolvaptan had a slower decline in kidney function and TKV expansion versus placebo. Those receiving both tolvaptan and metformin did not experience a statistically significant difference in eGFR decline or TKV expansion compared to other treatment groups. Adverse events were comparable between participants taking metformin with tolvaptan and other participant groups.
Conclusions: Overall, these data suggest that metformin may be safe to use in conjunction with tolvaptan and may not be associated with a higher incidence of adverse events. Low number of participants taking metformin at baseline resulted in insufficient data to determine the impact of co-therapy on clinical outcomes.
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