Diabetes Care: Safety comparison of sodium-glucose cotransporter 2 inhibitors, dipeptidyl peptidase 4 inhibitors and sulfonylureas for the risk of diabetic ketoacidosis

Objective: To evaluate the association of sodium-glucose cotransporter 2 (SGLT2) inhibitors with diabetic ketoacidosis compared with dipeptidyl peptidase 4 (DPP-4) inhibitors and sulfonylureas
.

To assess the association of sodium-glucose cotransporter 2 (SGLT2) inhibitors with diabetic ketoacidosis compared with dipeptidyl peptidase 4 (DPP-4) inhibitors and sulfonylureas
.

STUDY DESIGN AND METHODS: We conducted a comparative cohort study with active new users to examine two pairwise comparisons: 1) SGLT2 inhibitors versus DPP-4 inhibitors, and 2) SGLT2 inhibitors versus sulfonylureas
.

The primary outcome was diabetic ketoacidosis at the time of hospitalization

RESULTS: In Cohort 1 (n = 85,125 for SGLT2 inhibitors and n = 85,125 for DPP-4 inhibitors), the incidence of diabetic ketoacidosis per 1000 person-years was 6.
0 and 4.
3 for SGLT2 inhibitors and 4.
3 for DPP4 inhibitors, respectively
.

In cohort 2 (n = 72,436 SGLT2 inhibitors and n = 72,436 sulfonylureas), the incidence of diabetic ketoacidosis per 1000 person-years was 6.

Figure 1 Distribution of propensity scores before and after pairing of sodium-glucose co-transporter-2 inhibitors with dipeptidyl peptidase-4 inhibitors (group A) and sulfonylureas (group B) new users

Figure 1 Distribution of propensity scores before and after pairing of sodium-glucose co-transporter-2 inhibitors with dipeptidyl peptidase-4 inhibitors (group A) and sulfonylureas (group B) new users

Table 1 Incidence of diabetic ketoacidosis with sodium-glucose co-transporter-2 inhibitors compared with dipeptidyl peptidase-4 inhibitors and sulfonylureas in patients with type 2 diabetes

Table 1 Incidence of diabetic ketoacidosis with sodium-glucose co-transporter-2 inhibitors compared with dipeptidyl peptidase-4 inhibitors and sulfonylureas in patients with type 2 diabetes

Table 2 Baseline laboratory measurements in a subset of matched patients with type 2 diabetes who were new to sodium-glucose cotransporter-2 inhibitors compared to dipeptidyl peptidase-4 inhibitors and sulfonylureas

Table 2 Baseline laboratory measurements in a subset of matched patients with type 2 diabetes who were new to sodium-glucose cotransporter-2 inhibitors compared to dipeptidyl peptidase-4 inhibitors and sulfonylureas

Figure 2 E-values ​​representing combined minimum association strengths on the hazard ratio scale, unmeasured confounders must use SGLT2is or DPP4is and diabetic ketoacidosis (group A) or sulfonylureas (group B) to fully explain The observed treatment-outcome hazard ratios (SGLT2is vs.
DPP4is) and 1.
56 (SGLT2is vs.
sulfonylureas) were 1.
63 (SGLT2is vs.
DPP4is) and 1.
56 (SGLT2is vs.
sulfonylureas)
.

Figure 2 E-values ​​representing combined minimum association strengths on the hazard ratio scale, unmeasured confounders must use SGLT2is or DPP4is and diabetic ketoacidosis (group A) or sulfonylureas (group B) to fully explain The observed treatment-outcome hazard ratios (SGLT2is vs.
DPP4is) and 1.
56 (SGLT2is vs.
sulfonylureas) were 1.
63 (SGLT2is vs.
DPP4is) and 1.
56 (SGLT2is vs.
sulfonylureas)
.

Conclusions: In this comparative safety study, patients with type 2 diabetes treated with SGLT2 inhibitors had a higher incidence of diabetic ketoacidosis compared with DPP-4 inhibitors and sulfonylureas
.

Clinicians should be wary of this association

In this comparative safety study, patients with type 2 diabetes treated with SGLT2 inhibitors had a higher incidence of diabetic ketoacidosis compared with DPP-4 inhibitors and sulfonylureas

Comparative Safety of Sodium-Glucose Cotransporter 2 Inhibitors Versus Dipeptidyl Peptidase 4 Inhibitors and Sulfonylureas on the Risk of Diabetic Ketoacidosis.
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