Sodium/Glucose Cotransporter 2 Inhibitors and the Risk of Diabetic Ketoacidosis: An Example of Complementary Evidence for Rare Adverse Events. Issue 8 (6th March 2021)

• Record Type: Journal Article
• Authors: Alkabbani, Wajd; Pelletier, Ryan; Gamble, John-Michael
• Is Part Of: American journal of epidemiology. Volume 190:Issue 8(2021)
• Page Start: 1572
• Page End: 1581
• Publication Date: 2021-03-06
• Subjects: adverse events -- diabetic ketoacidosis -- meta-analysis -- rare safety outcomes -- SGLT-2 inhibitors -- sodium/glucose cotransporter 2 -- systematic reviews; Epidemiology -- Periodicals; Public health -- Periodicals; 614.4
• DOI: 10.1093/aje/kwab052
• Languages: English
• ISSNs: 0002-9262

Abstract

Abstract: Evidence from observational studies may be considered complementary to that of randomized controlled trials (RCTs), particularly when assessing rare outcomes of drug therapies. Sodium/glucose cotransporter 2 (SGLT-2) inhibitors are a novel class of antidiabetic agents that have been linked to an increased risk of diabetic ketoacidosis (DKA). We conducted a systematic review and separately meta-analyzed data from RCTs ( n = 18; 2013–2019) and cohort studies ( n = 7; 2017–2020) to assess the consistency of the magnitude of association between SGLT-2 inhibitors and DKA risk. We illustrate the strengths and weaknesses of the 2 designs. Results from RCTs and observational studies consistently showed almost a doubling in the risk of DKA among patients using an SGLT-2 inhibitor as compared with placebo or an active comparator. In a random-effects model, the pooled relative risk was 2.08 (95% confidence interval (CI): 1.28, 3.40) from placebo-controlled RCTs and 0.82 (95% CI: 0.25, 2.68) from active-comparator RCTs. The pooled adjusted hazard ratio from observational studies was 1.74 (95% CI: 1.28, 2.38). Notably, the 2 designs complement each other in several domains, including external and internal validity and power. This demonstrates a need for more comprehensive evidence when assessing rare adverse events for both sources.