TY - JOUR
T1 - Safety of Sodium-Glucose Co-Transporter 2 Inhibitors
AU - McGill, Janet B.
AU - Subramanian, Savitha
N1 - Funding Information:
Funding: This work was supported by Boehringer Ingelheim Pharmaceuticals, Inc. Writing support was provided by Debra Brocksmith, MB ChB, PhD, of Elevate Scientific Solutions, which was contracted and funded by Boehringer Ingelheim Pharmaceuticals, Inc. The authors received no direct or indirect compensation related to the development of the manuscript. Publication of this supplement was supported by the Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance. Conflicts of Interest: JBM reports nonfinancial support from Boehringer Ingelheim; personal fees from Aegerion, Bayer, Boehringer Ingelheim, Gilead, Janssen, and Novo Nordisk; grants and personal fees from Dexcom and Sanofi; grants from AstraZeneca, Medtronic, and Novartis; personal fees and nonfinancial support from Mannkind. SS has none.
Publisher Copyright:
© 2019
PY - 2019/10
Y1 - 2019/10
N2 - Sodium-glucose co-transporter 2 (SGLT2) inhibitors have a well-defined safety profile based on data obtained from numerous clinical trials, including cardiovascular outcomes trials (CVOTs) and postmarketing pharmacovigilance reporting. Adverse events including risk of genital mycotic infection and volume depletion-related events are consistent with the mechanism of action of this drug class. However, several emergent (albeit infrequent) serious safety issues have also been reported. In their respective CVOTs, the proportion of patients with reported diabetic ketoacidosis was similar in empagliflozin or canagliflozin compared with their placebo groups, but it was higher for dapagliflozin. Canagliflozin may be associated with an increased risk of bone fracture and lower limb amputation; however, data are inconclusive. There is no evidence linking SGLT2 inhibitors with an increased risk of cancer, but these agents, particularly dapagliflozin, should be used with caution in patients with hematuria or a history of bladder cancer. Postmarketing reports of acute kidney injury have occurred in patients receiving SGLT2 inhibitors, and cases identified in recent CVOTs occurred with similar frequency in SGLT2 inhibitor and placebo groups. Common adverse events associated with SGLT2 inhibitors (such as genital infections or volume depletion) are generally mild and manageable by patients or by primary care physicians, and the risk of rare events (such as ketoacidosis) can be minimized by appropriate patient selection and early recognition of symptoms. When selecting treatment, it is important that clinicians weigh the known risks of SGLT2 inhibitors against their proven benefits, including the reduction of adverse cardiovascular and renal outcomes.
AB - Sodium-glucose co-transporter 2 (SGLT2) inhibitors have a well-defined safety profile based on data obtained from numerous clinical trials, including cardiovascular outcomes trials (CVOTs) and postmarketing pharmacovigilance reporting. Adverse events including risk of genital mycotic infection and volume depletion-related events are consistent with the mechanism of action of this drug class. However, several emergent (albeit infrequent) serious safety issues have also been reported. In their respective CVOTs, the proportion of patients with reported diabetic ketoacidosis was similar in empagliflozin or canagliflozin compared with their placebo groups, but it was higher for dapagliflozin. Canagliflozin may be associated with an increased risk of bone fracture and lower limb amputation; however, data are inconclusive. There is no evidence linking SGLT2 inhibitors with an increased risk of cancer, but these agents, particularly dapagliflozin, should be used with caution in patients with hematuria or a history of bladder cancer. Postmarketing reports of acute kidney injury have occurred in patients receiving SGLT2 inhibitors, and cases identified in recent CVOTs occurred with similar frequency in SGLT2 inhibitor and placebo groups. Common adverse events associated with SGLT2 inhibitors (such as genital infections or volume depletion) are generally mild and manageable by patients or by primary care physicians, and the risk of rare events (such as ketoacidosis) can be minimized by appropriate patient selection and early recognition of symptoms. When selecting treatment, it is important that clinicians weigh the known risks of SGLT2 inhibitors against their proven benefits, including the reduction of adverse cardiovascular and renal outcomes.
KW - Adverse events
KW - Safety
KW - Sodium-glucose co-transporter 2 inhibitors
UR - http://www.scopus.com/inward/record.url?scp=85074211327&partnerID=8YFLogxK
U2 - 10.1016/j.amjmed.2019.08.006
DO - 10.1016/j.amjmed.2019.08.006
M3 - Review article
C2 - 31741440
AN - SCOPUS:85074211327
SN - 0002-9343
VL - 132
SP - S49-S57.e5
JO - American Journal of Medicine
JF - American Journal of Medicine
IS - 10
ER -