The impact of diabetes mellitus on the pharmacokinetics of rifampicin among tuberculosis patients: A systematic review and meta-analysis study

Background and aims Diabetes mellitus has a negative impact on the treatment outcome of tuberculosis, increasing the incidence of treatment failure and relapse. There is a scarcity of knowledge concerning the impact of diabetes mellitus on the pharmacokinetics of rifampicin. This study was conducted to evaluate the impact of diabetes mellitus on the pharmacokinetics of rifampicin among patients with tuberculosis. Methods We explored the Web of Science, Cochrane Library, PubMed, and Scopus databases for articles that reported the pharmacokinetic parameters of rifampicin in diabetic and nondiabetic patients with tuberculosis published until September 2020. Based on the presence or absence of heterogeneity, pooled estimates were calculated using a random or fixed effect model. Results Seven studies were relevant and included in this study. The Tmax of rifampicin increased in diabetic patients with tuberculosis compared with nondiabetic patients with tuberculosis (MD 0.84, 95% CI (0.32, 1.35), p = 0.002). No significant differences were detected in rifampicin Cmax (MD 0.18, 95% CI (-0.52, 0.88), p = 0.61), AUC0-24 (SMD -0.02, 95% CI (-0.34, 0.30), p = 0.90), Vd (MD -3.89, 95% CI (-11.17, 3.38), p = 0.29), CL (MD -0.13, 95%CI (-0.88, 0.61), p = 0.72), and MRT (MD 1.89, 95% CI (-0.03, 3.81), p = 0.05) between diabetic and nondiabetic patients with tuberculosis. Conclusion Diabetes mellitus increased the Tmax of rifampicin without further impact on other rifampicin pharmacokinetic parameters such as Cmax, AUC0-24, Vd, CL and MRT. Early therapeutic drug monitoring of rifampicin is necessary for diabetic tuberculosis patients.