PMID- 29174026
OWN - NLM
STAT- MEDLINE
DCOM- 20171218
LR  - 20181202
IS  - 1590-3729 (Electronic)
IS  - 0939-4753 (Linking)
VI  - 27
IP  - 12
DP  - 2017 Dec
TI  - Adverse events with sodium-glucose co-transporter-2 inhibitors: A global analysis 
      of international spontaneous reporting systems.
PG  - 1098-1107
LID - S0939-4753(17)30235-1 [pii]
LID - 10.1016/j.numecd.2017.10.008 [doi]
AB  - BACKGROUND AND AIMS: We assessed post-marketing safety of sodium-glucose 
      co-transporter-2 inhibitors (SGLT2-Is) by analyzing adverse events (AEs) reported 
      in international pharmacovigilance databases. METHODS AND RESULTS: 
      Eudravigilance, WHO-Vigibase (as of Feb 25, 2017) and the FDA Adverse Event 
      Reporting System (FAERS, from 2004 to 2016 second quarter) were queried to 
      extract AEs recording SGLT2-Is as suspect. Disproportionality analyses 
      (case/non-case method) were performed in FAERS by calculating the reporting odds 
      ratios (RORs) from System Organ Classes (SOCs) to Preferred Terms (PTs) (precise 
      clinical entities). Potential signals were defined by statistically-significant 
      ROR (lower limit of the 95% confidence interval - LL95%CI - >1) undetected by 
      literature analysis (as of December 2016). SGLT2-Is were recorded in 7972, 
      19,775, 11,137 reports (Eudravigilance, WHO-Vigibase and FAERS, respectively); in 
      FAERS, statistically significant ROR emerged for the following SOCs: "infections 
      and infestations" (N = 2162; LL95%CI = 3.25), "metabolism and nutrition 
      disorders" (2278; 1.36), "renal and urinary disorders" (1665; 2.31), 
      "reproductive system and breast disorders" (471; 4.85), "skin and subcutaneous 
      tissue disorders" (1136; 1.52). Skin toxicity emerged as potential signal (e.g., 
      rash, photosensitivity, urticaria as PTs), both for SGLT2-Is as a class and as 
      individual drugs. Severe adverse skin events (81 reports, 7% of the skin cases) 
      mainly occurred in females aged 18-65 using SGLT2-Is as single antidiabetic 
      regimen. CONCLUSION: Among antidiabetics, SGLT2-Is are associated with higher 
      reporting of infections, metabolism, renal and reproductive AEs, corroborating 
      clinical trial evidence. Their large reporting patterns and the unexpected signal 
      of skin toxicity justify active vigilance by clinicians and "real-time" 
      monitoring by pharmacovigilance experts.
CI  - Copyright (c) 2017 The Italian Society of Diabetology, the Italian Society for the 
      Study of Atherosclerosis, the Italian Society of Human Nutrition, and the 
      Department of Clinical Medicine and Surgery, Federico II University. Published by 
      Elsevier B.V. All rights reserved.
FAU - Raschi, E
AU  - Raschi E
AD  - Pharmacology Unit, Department of Medical and Surgical Sciences, University of 
      Bologna, Bologna, Italy.
FAU - Parisotto, M
AU  - Parisotto M
AD  - Pharmacology Unit, Department of Medical and Surgical Sciences, University of 
      Bologna, Bologna, Italy.
FAU - Forcesi, E
AU  - Forcesi E
AD  - Pharmacology Unit, Department of Medical and Surgical Sciences, University of 
      Bologna, Bologna, Italy.
FAU - La Placa, M
AU  - La Placa M
AD  - Dermatology Division, Department of Experimental, Diagnostic and Specialty 
      Medicine, University of Bologna, Bologna, Italy.
FAU - Marchesini, G
AU  - Marchesini G
AD  - Unit of Metabolic Diseases & Clinical Dietetics, Department of Medical and 
      Surgical Sciences, University of Bologna, Bologna, Italy.
FAU - De Ponti, F
AU  - De Ponti F
AD  - Pharmacology Unit, Department of Medical and Surgical Sciences, University of 
      Bologna, Bologna, Italy.
FAU - Poluzzi, E
AU  - Poluzzi E
AD  - Pharmacology Unit, Department of Medical and Surgical Sciences, University of 
      Bologna, Bologna, Italy. Electronic address: elisabetta.poluzzi@unibo.it.
LA  - eng
PT  - Journal Article
DEP - 20171018
PL  - Netherlands
TA  - Nutr Metab Cardiovasc Dis
JT  - Nutrition, metabolism, and cardiovascular diseases : NMCD
JID - 9111474
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (SLC5A2 protein, human)
RN  - 0 (Sodium-Glucose Transporter 2)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - *Adverse Drug Reaction Reporting Systems
MH  - Aged
MH  - Child
MH  - Child, Preschool
MH  - Databases, Factual
MH  - Diabetes Mellitus, Type 2/*drug therapy/metabolism
MH  - Drug-Related Side Effects and Adverse Reactions/diagnosis/*epidemiology
MH  - Female
MH  - Humans
MH  - Hypoglycemic Agents/*adverse effects
MH  - Infant
MH  - Infant, Newborn
MH  - Male
MH  - Middle Aged
MH  - Patient Safety
MH  - *Pharmacovigilance
MH  - Risk Assessment
MH  - Risk Factors
MH  - Sodium-Glucose Transporter 2/metabolism
MH  - *Sodium-Glucose Transporter 2 Inhibitors
MH  - Time Factors
MH  - Young Adult
OTO - NOTNLM
OT  - Disproportionality
OT  - Gliflozins
OT  - Pharmacovigilance
OT  - Skin toxicity
OT  - Sodium-glucose co-transporter-2 inhibitors
OT  - Spontaneous reporting system
EDAT- 2017/11/28 06:00
MHDA- 2017/12/19 06:00
CRDT- 2017/11/28 06:00
PHST- 2017/07/14 00:00 [received]
PHST- 2017/09/19 00:00 [revised]
PHST- 2017/10/06 00:00 [accepted]
PHST- 2017/11/28 06:00 [pubmed]
PHST- 2017/12/19 06:00 [medline]
PHST- 2017/11/28 06:00 [entrez]
AID - S0939-4753(17)30235-1 [pii]
AID - 10.1016/j.numecd.2017.10.008 [doi]
PST - ppublish
SO  - Nutr Metab Cardiovasc Dis. 2017 Dec;27(12):1098-1107. doi: 
      10.1016/j.numecd.2017.10.008. Epub 2017 Oct 18.