Abstract
Abstract Objective Sodium-glucose cotransporter-2 (SGLT2) inhibitors are very effective in reducing hemoglobin A1c. They also have benefits in reducing cardiovascular events, heart failure hospitalization, and progression of renal disease in patients with and without T2DM. However, FDA issued a warning for a possible severe UTI. Conversely, the evidence from randomized clinical trials and observational studies is limited and controversial. Therefore, we aimed to investigate the association of urosepsis and SGLT-2 inhibitors using the method of systematic review and meta-analysis. Methods Potentially eligible studies were identified from MEDLINE, Scopus, EMBASE, Ovid, and the Cochrane Library from inception to September 2020 with the help of an experienced librarian aiming to identify studies reporting the number of adults users of any SGLT2 inhibitor (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, luseogliflozin, remogliflozin, and tofogliflozin) who developed urosepsis, compared to those who never used SGLT2 inhibitors. The following exclusion criteria were used: only abstracts or pilot data, studies reporting rates of urosepsis only in SGLT2 inhibitors users without comparison, or studies with a comparison group in which SGLT2 was not the only differential treatment. Results In total, 1203 papers were identified with our search strategies, of which 169 were evaluated as full text, and 6 studies were finally selected for the meta-analysis after two rounds of the independent review by five investigators. The overall risk of bias of the included studies was low-to-moderate. We found no difference in the risk of urosepsis in users of SGLT2 inhibitors (OR= 1.34; 95% CI, 0.79 to 2.28; P=0.28; I2=48%) compared to the comparison group. In a subgroup analysis by the type of SGLT2 inhibitor evaluated we found no differences between dapagliflozin (OR= 0.92; 95% CI, 0.51 to 1.67; P=0.82; I2=0%) or canagliflozin (OR= 0.32; 95% CI, 0. 03 to 3.63; P=0.27; I2=17%) users in the risk of urosepsis. Publication bias was assessed by performing funnel plots which showed visual asymmetry suggestion potential publication bias. Discussion/Conclusion In this systematic review and meta-analysis, including 6 publications and 456301 participants, we found that individuals treated with SGLT2 inhibitors do not have a significantly higher risk of urosepsis than individuals of the comparison group. Additionally, no differences were found in the risk of urosepsis when each SLGT2 inhibitor agent was assessed separately. Presentation: No date and time listed
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