Study Reveals Dose-Dependent Risk of DKA with SGLT2 Inhibitors in Type 1 Diabetes

Drawing on data from 19 clinical studies, the findings indicated that dapagliflozin, empagliflozin, and sogliflozin were linked to a higher risk of DKA. In contrast, canagliflozin at a dose of 300 milligrams was associated with the lowest risk.

The advantages of sodium-glucose cotransporter-2 (SGLT2) inhibitors in managing type 1 diabetes mellitus (T1DM) are well-established, but their application is constrained by the risk of diabetic ketoacidosis (DKA). The impact of varying SGLT2 inhibitor doses on DKA risk in T1DM remains unclear. Therefore, Ying Liu, Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China, and colleagues performed a network meta-analysis to assess the incidence of DKA across different dosages in T1DM treatment.

For this purpose, the researchers conducted a network meta-analysis to evaluate the incidence of DKA at different doses in the treatment of T1DM. They searched electronic databases and clinical trial registries, including PubMed, Embase (Ovid SP), the Cochrane Central Register of Controlled Trials (Ovid SP), and ClinicalTrials.gov, for randomized controlled trials (RCTs) involving SGLT2 inhibitors in patients with T1DM from inception to December 2023.

Two researchers independently performed literature screening, quality assessment, and data extraction according to the inclusion and exclusion criteria. They conducted a statistical analysis using Stata 15.1 and R 4.1.3 software.

Based on the study, the researchers reported the following findings:

• Nineteen clinical studies and one clinical trial were included in the analysis.

• Five different SGLT2 inhibitors were evaluated.

• The incidence of DKA was significantly higher compared to placebo for the following:

• Dapagliflozin 5 mg (OR: 2.57).

• Empagliflozin 10 mg (OR: 2.68).

 • Sogliflozin 200 mg (OR: 4.04).

• Sogliflozin 400 mg (OR: 5.96).

• Based on P scores, SGLT2 inhibitors triggered a lower overall incidence of DKA than the placebo.

• Treatment with 300 mg of canagliflozin demonstrated the lowest incidence of DKA.

"Our study found that the use of 5 mg dapagliflozin, 10 mg empagliflozin, 200 mg sogliflozin, and 400 mg sogliflozin in combination with insulin for treating T1DM was associated with an increased risk of DKA. Other SGLT2 inhibitors appeared to have a safer profile. However, it is important to note that SGLT2 inhibitors are not approved for treating T1DM in China, and their use requires close monitoring for potential adverse reactions,"

Reference:

Liu, Y., Yang, S., Jiang, A., Dan, Z., Zhao Yang, C., & Su, N. Risk of diabetic ketoacidosis caused by sodium glucose cotransporter-2 inhibitors in patients with type 1 diabetes: A systematic review and network meta-analysis of randomized controlled trials. Frontiers in Endocrinology, 15, 1453067. https://doi.org/10.3389/fendo.2024.1453067