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IMPORTANCE Use of the sodium-glucose cotransporter 2 inhibitor empagliflozin has increased substantially since 2015. Little is known about characteristics of real-world patients who use empagliflozin or about empagliflozin's effectiveness in reducing glycated hemoglobin (HbA 1c) levels in routine clinical care. OBJECTIVES To characterize real-world initiators of empagliflozin, to examine the proportion of initiators who would have been eligible for participation in phase 3 randomized clinical trials (RCTs) of empagliflozin, and to assess changes in HbA 1c levels after empagliflozin initiation. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study used linked population-based medical databases containing complete information on redeemed prescriptions, laboratory tests, and diagnoses for all residents in Northern Denmark. A total of 7034 residents of Denmark who filled a first-time empagliflozin prescription from January 2014 to December 2018 were included. Data analysis was performed in August 2019. EXPOSURE Empagliflozin initiation. MAIN OUTCOMES AND MEASURES Proportion of real-world users ineligible for RCT inclusion and absolute reduction in HbA 1c level 6 months after empagliflozin initiation. RESULTS Of 7034 first-time empagliflozin initiators (median [interquartile range] age, 61.50 [53.30-69.38] years; 4475 [63.6%] men), 3878 (55.1%) would have been ineligible for phase 3 RCT participation; frequent reasons were concurrent use of specific glucose-lowering drugs (1955 initiators [27.8%]), baseline HbA 1c level outside the eligibility range (1772 [25.2%]), or presence of comorbidities (1067 initiators [15.3%]). Initiation of empagliflozin was associated with a mean HbA 1c reduction of −0.91% (95% CI, −0.94% to −0.87%) after 6 months, similar to phase 3 RCT results. Real-world empagliflozin initiators who would have been eligible for RCT participation experienced slightly lower mean HbA 1c reductions (−0.78%; 95% CI, −0.82% to −0.74%) compared with patients who would have been ineligible (−1.01%; 95% CI, −1.07% to −0.95%). Ineligible initiators had higher median (interquartile range) baseline HbA 1c values than eligible initiators (8.5% [7.4% to 10.1%] vs 8.2% [7.6% to 9.8%]). CONCLUSIONS AND RELEVANCE In this cross-sectional study, more than half of empagliflozin initiators exhibited clinical characteristics that would have led to ineligibility for the RCTs leading to the drug's approval. While the findings suggest that the efficacy of empagliflozin in reducing HbA 1c levels translates into real-world effectiveness, further studies should examine clinical outcome effectiveness and drug safety in routine clinical care.

Background The diagnostic performance of magnetic resonance imaging (MRI) modalities and/or endoscopy for assessing complete response in rectal cancer after neoadjuvant chemoradiotherapy (nCRT) is unclear. Purpose To summarize existing evidence on the diagnostic performance of diffusion-weighted MRI, perfusion-weighted MRI, T2-weighted MR tumor regression grade, and/or endoscopy for assessing complete tumor response after nCRT. Material and Methods MEDLINE and Embase databases were searched. The PRISMA guidelines were followed. Sensitivity, specificity, negative predictive, and positive predictive values were retrieved from included studies. Results In total, 81 studies were eligible for inclusion. Evidence suggests that combined use of MRI and endoscopy tends to improve the diagnostic performance compared to single imaging modality. The positive predictive value of a complete response varies substantially between studies. There is considerable heterogeneity between studies. Conclusion Combined re-staging tends to improve diagnostic performance compared to single imaging modality, but the vast majority of studies fail to offer true clinical value due to the study heterogeneity.