Gian Paolo Fadini1, Benedetta Maria Bonora2, Angelo Avogaro2. 1. Department of Medicine, University of Padova, Via Giustiniani 2, 35128, Padova, Italy. gianpaolo.fadini@unipd.it. 2. Department of Medicine, University of Padova, Via Giustiniani 2, 35128, Padova, Italy.
Abstract
AIMS/HYPOTHESIS: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are indicated for the treatment of type 2 diabetes and may also improve glucose control in type 1 diabetes. In 2015, regulatory agencies warned that SGLT2i may favour diabetic ketoacidosis (DKA). We provide a detailed analysis of DKA reports in which an SGLT2i was listed among suspect or concomitant drugs in the US Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: We first analysed the entire public FAERS up to September (third quarter [Q3]) 2016 to extract the number of reports, background indications and concomitant medications, and to calculate proportional reporting ratios (PRRs) and safety signals. We then mined single FAERS files from the first quarter (Q1) of 2014 to 2016 Q3 to obtain detailed information on DKA reports. RESULTS: The FAERS database contains >2500 DKA reports in which SGLT2i are listed as suspect or concomitant drugs. The PRR of DKA in reports including vs those not including an SGLT2i and having a diabetes indication was 7.9 (95% CI 7.5, 8.4) and was higher for type 1 diabetes. Several concomitant conditions were less prevalent in DKA reports with SGLT2i vs DKA reports filed for other drugs. A detailed analysis of 2397 DKA reports for SGLT2i from 2014 Q1 to 2016 Q3 revealed a predominance of women, an extremely wide range of age and body weight, and a highly variable duration of SGLT2i treatment before onset of DKA. In 37 individuals (1.54%), DKA was fatal. CONCLUSIONS/ INTERPRETATION: Based on the profile of these reports, SGLT2i-associated DKA may not be limited to any particular demographic or comorbid subpopulation and can occur at any duration of SGLT2i use. DATA AVAILABILITY: A list of FDA reports analysed in the study is available in the figshare repository, 10.6084/m9.figshare.4903211 . Other data are available from the corresponding author on reasonable request.
AIMS/HYPOTHESIS: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are indicated for the treatment of type 2 diabetes and may also improve glucose control in type 1 diabetes. In 2015, regulatory agencies warned that SGLT2i may favour diabetic ketoacidosis (DKA). We provide a detailed analysis of DKA reports in which an SGLT2i was listed among suspect or concomitant drugs in the US Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: We first analysed the entire public FAERS up to September (third quarter [Q3]) 2016 to extract the number of reports, background indications and concomitant medications, and to calculate proportional reporting ratios (PRRs) and safety signals. We then mined single FAERS files from the first quarter (Q1) of 2014 to 2016 Q3 to obtain detailed information on DKA reports. RESULTS: The FAERS database contains >2500 DKA reports in which SGLT2i are listed as suspect or concomitant drugs. The PRR of DKA in reports including vs those not including an SGLT2i and having a diabetes indication was 7.9 (95% CI 7.5, 8.4) and was higher for type 1 diabetes. Several concomitant conditions were less prevalent in DKA reports with SGLT2i vs DKA reports filed for other drugs. A detailed analysis of 2397 DKA reports for SGLT2i from 2014 Q1 to 2016 Q3 revealed a predominance of women, an extremely wide range of age and body weight, and a highly variable duration of SGLT2i treatment before onset of DKA. In 37 individuals (1.54%), DKA was fatal. CONCLUSIONS/ INTERPRETATION: Based on the profile of these reports, SGLT2i-associated DKA may not be limited to any particular demographic or comorbid subpopulation and can occur at any duration of SGLT2i use. DATA AVAILABILITY: A list of FDA reports analysed in the study is available in the figshare repository, 10.6084/m9.figshare.4903211 . Other data are available from the corresponding author on reasonable request.
Entities:
Keywords:
Case report; Glucose-lowering medications; Pharmacovigilance; Therapy
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