Reporting of sodium-glucose cotransporter 2 (SGLT2) inhibitor trial safety: an observational analysis of ClinicalTrials.gov registrations and journal publications.

BACKGROUND AND

OBJECTIVES

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have gained prominence over the last decade due to their multifaceted benefits. However, systematic reviews and meta-analyses reveal conflicting results regarding their adverse event profiles compared to placebo. This study aimed to compare safety data from clinical trials on SGLT2 inhibitors reported in ClinicalTrials.gov with data published in scholarly journals.

METHODS

In this observational, cross-sectional study, we included clinical trials on SGLT2 inhibitors registered at ClinicalTrials.gov with a matching publication in a scholarly journal with full text available. From ClinicalTrials.gov and the corresponding publication, we extracted data on the number of serious adverse events (SAEs), the number of patients with SAEs, all-cause mortality (ACM), and the number of deaths. We analyzed the consistency of data between the registry and publications.

RESULTS

In 176 included trials, comparisons of safety data between ClinicalTrials.gov and corresponding publications indicated discrepancies for the total number of patients with SAE in 70 (40%) trials, for the reported overall number of SAEs in 77 (44%) trials and ACM in 27 (34%) trials. Overall, trialists reported 33,303 patients with SAEs in ClinicalTrials.gov, compared to 28,118 in matching publications (difference 5185; χ2 = 22,808, P < .001). For the number of SAEs, there were 44,163 SAEs reported in ClinicalTrials.gov, compared to 28,151 SAEs reported in publications (difference 16,012; χ2 = 196,897, P < .001). Compared to the registrations, 17 (21%) trials reported fewer deaths (a total of 4106 fewer deaths), and 8 (10%) trials reported more deaths (43 more deaths) in the publication. Industry-sponsored trials were significantly more likely to report the same number of ACM in registrations and publications (χ2 = 22.72, P < .001). Trials on dapagliflozin had the highest rate of discrepant reporting in publications compared to other medicines.

CONCLUSION

The pronounced discrepancies in mortality and SAEs data for SGLT2 inhibitors between clinical trial registries and journal publications highlight the need for improved alignment and transparency in safety reporting. Strengthening reporting standards and editorial processes may enhance the consistency and interpretability of trial safety data.