Ippazio Cosimo Antonazzo1, Elisabetta Poluzzi1, Emanuele Forcesi1, Francesco Salvo2,3,4, Antoine Pariente2,3,4, Giulio Marchesini5, Fabrizio De Ponti1, Emanuel Raschi6. 1. Pharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Via Irnerio, 48, 40126, Bologna, BO, Italy. 2. University of Bordeaux, U657, 33000, Bordeaux, France. 3. INSERM U657, 33000, Bordeaux, France. 4. CIC Bordeaux CICI1401, 33000, Bordeaux, France. 5. Unit of Metabolic Diseases and Clinical Dietetics, Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy. 6. Pharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Via Irnerio, 48, 40126, Bologna, BO, Italy. emanuel.raschi@unibo.it.
Abstract
AIMS: To investigate the occurrence of myopathy with oral glucose-lowering drugs (OGLDs) and statins, with a focus on dipeptidyl peptidase-4 inhibitors (DPP4-is). METHODS: The FDA adverse event reporting system (FAERS) was queried (2004-2016) to compare the proportion of adverse events with OGLDs, alone and in combination with statins, using the reporting odds ratio (ROR) with relevant 95% confidence interval (95%Cl), adjusted for sex, age and concomitant presence of other OGLDs/lipid-lowering drugs. Drug-drug interaction is claimed whenever the frequency of an event is enhanced by combination treatment. Consistency/robustness of findings was tested by applying additive/multiplicative models and accounting for competition bias (i.e., adverse events previously known to be associated with OGLDs were removed). RESULTS: Over a 13-year period, we retrieved 142,888 cases of myopathy. The use of DPP4-is alone was not associated with higher reporting of myopathy (no. of cases = 4898; adjusted ROR = 1.00; 95%CI = 0.96-1.04), with the notable exclusion of vildagliptin (262; 1.64; 1.42-1.88). No increased occurrence emerged when used in combination with statins, with consistent findings from additive/multiplicative models for all DPP4-is. Likewise, no increased reporting was found for other OGLDs (28,964; 0.64; 0.62-0.67); data on the interaction with statins were consistent/robust across analyses only for sulfonylureas (the interaction is likely and biologically plausible) and sodium glucose cotransporter-2 inhibitors. CONCLUSIONS: Real-world FAERS data do not raise concern for muscular toxicity with DPP4-is in combination with statins, making a drug interaction very unlikely.
AIMS: To investigate the occurrence of myopathy with oral glucose-lowering drugs (OGLDs) and statins, with a focus on dipeptidyl peptidase-4 inhibitors (DPP4-is). METHODS: The FDA adverse event reporting system (FAERS) was queried (2004-2016) to compare the proportion of adverse events with OGLDs, alone and in combination with statins, using the reporting odds ratio (ROR) with relevant 95% confidence interval (95%Cl), adjusted for sex, age and concomitant presence of other OGLDs/lipid-lowering drugs. Drug-drug interaction is claimed whenever the frequency of an event is enhanced by combination treatment. Consistency/robustness of findings was tested by applying additive/multiplicative models and accounting for competition bias (i.e., adverse events previously known to be associated with OGLDs were removed). RESULTS: Over a 13-year period, we retrieved 142,888 cases of myopathy. The use of DPP4-is alone was not associated with higher reporting of myopathy (no. of cases = 4898; adjusted ROR = 1.00; 95%CI = 0.96-1.04), with the notable exclusion of vildagliptin (262; 1.64; 1.42-1.88). No increased occurrence emerged when used in combination with statins, with consistent findings from additive/multiplicative models for all DPP4-is. Likewise, no increased reporting was found for other OGLDs (28,964; 0.64; 0.62-0.67); data on the interaction with statins were consistent/robust across analyses only for sulfonylureas (the interaction is likely and biologically plausible) and sodium glucose cotransporter-2 inhibitors. CONCLUSIONS: Real-world FAERS data do not raise concern for muscular toxicity with DPP4-is in combination with statins, making a drug interaction very unlikely.
Entities:
Keywords:
Antidiabetic drugs; Drug interactions; FAERS; Myopathy
Authors: Wajd Alkabbani; Ryan Pelletier; Michael A Beazely; Youssef Labib; Breanna Quan; John-Michael Gamble Journal: Drug Saf Date: 2022-03-05 Impact factor: 5.228