Sodium glucose cotransporter 2 inhibitors and risk of serious adverse events: nationwide register based cohort study.

Peter Ueda, Henrik Svanström, Mads Melbye, Björn Eliasson, Ann-Marie Svensson, Stefan Franzén, Soffia Gudbjörnsdottir, Kristian Hveem, Christian Jonasson, Björn Pasternak

REVIEW


11 June 2019

There is a great deal of interest in this topic area, given the CANVAS and EMPA-REG trials and the need to evaluate both classes of drug as 2nd and 3rd line therapies for T2DM.  This study adds to the literature by exploring SGLT2s and GLP1 s in the real-world setting, and in a larger population.


RELEVANCE 3
INNOVATIVENESS 3
APPLICABILITY 3
OVERALL 3

PAPER DETAILS


TITLE

Sodium glucose cotransporter 2 inhibitors and risk of serious adverse events: nationwide register based cohort study.

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 1.1 events per 1000 person years, hazard ratio 2.32, 95% confidence interval 1.37 to 3.91) and diabetic ketoacidosis (1.3 0.6, 2.14, 1.01 to 4.52) but not with bone fracture (15.4 13.9, 1.11, 0.93 to 1.33), acute kidney injury (2.3 3.2, 0.69, 0.45 to 1.05), serious urinary tract infection (5.4 6.0, 0.89, 0.67 to 1.19), venous thromboembolism (4.2 4.1, 0.99, 0.71 to 1.38) or acute pancreatitis (1.3 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.



AUTHOR(S)

Peter Ueda, Henrik Svanström, Mads Melbye, Björn Eliasson, Ann-Marie Svensson, Stefan Franzén, Soffia Gudbjörnsdottir, Kristian Hveem, Christian Jonasson, Björn Pasternak,

JOURNAL

BMJ (Clinical research ed.)

PLACE

England