Abstract
Abstract
Objective
To assess the association between the use of sodium glucose cotransporter 2 (SGLT2) inhibitors and seven serious adverse events of current concern.
Design
Register based cohort study.
Setting
Sweden and Denmark from July 2013 to December 2016.
Participants
A propensity score matched cohort of 17 213 new users of SGLT2 inhibitors (dapagliflozin, 61%; empagliflozin, 38%; canagliflozin, 1%) and 17 213 new users of the active comparator, glucagon-like peptide 1 (GLP1) receptor agonists.
Main outcome measures
The primary outcomes were lower limb amputation, bone fracture, diabetic ketoacidosis, acute kidney injury, serious urinary tract infection, venous thromboembolism, and acute pancreatitis, as identified from hospital records. Hazard ratios and 95% confidence intervals were estimated by using Cox proportional hazards models.
Results
Use of SGLT2 inhibitors, as compared with GLP1 receptor agonists, was associated with an increased risk of lower limb amputation (incidence rate 2.7
v
1.1 events per 1000 person years, hazard ratio 2.32, 95% confidence interval 1.37 to 3.91) and diabetic ketoacidosis (1.3
v
0.6, 2.14, 1.01 to 4.52) but not with bone fracture (15.4
v
13.9, 1.11, 0.93 to 1.33), acute kidney injury (2.3
v
3.2, 0.69, 0.45 to 1.05), serious urinary tract infection (5.4
v
6.0, 0.89, 0.67 to 1.19), venous thromboembolism (4.2
v
4.1, 0.99, 0.71 to 1.38) or acute pancreatitis (1.3
v
1.2, 1.16, 0.64 to 2.12).
Conclusions
In this analysis of nationwide registers from two countries, use of SGLT2 inhibitors, as compared with GLP1 receptor agonists, was associated with an increased risk of lower limb amputation and diabetic ketoacidosis, but not with other serious adverse events of current concern.
Reference48 articles.
1. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes
2. U.S. Food and Drug Administration. FDA Drug Safety Communication: FDA revises labels of SGLT2 inhibitors for diabetes to include warnings about too much acid in the blood and serious urinary tract infections. https://www.fda.gov/downloads/Drugs/DrugSafety/UCM475487.pdf.
3. Ketoacidosis associated with SGLT2 inhibitor treatment: Analysis of FAERS data
4. U.S. Food and Drug Administration. FDA Drug Safety Communication: FDA strengthens kidney warnings for diabetes medicines canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR). https://www.fda.gov/downloads/Drugs/DrugSafety/UCM506772.pdf
5. Acute renal failure with sodium-glucose-cotransporter-2 inhibitors: Analysis of the FDA adverse event report system database