3818 Comparing age, comorbidity and event rates between SGLT2 inhibitor trial participants and people treated in routine care

Abstract Introduction Randomised controlled trials are often criticised for excluding older people with multiple long-term conditions. This study used individual participant data (IPD) for 25 trials of sodium glucose co-transporter-2 inhibitors (SGLT2i) to compare baseline characteristics, comorbidities, and event rates between trial participants and community SGLT2i-treated people. Methods Trials were identified through a systematic review with subsequent application for IPD. Community SGLT2i-treated people in routine care were identified from SAIL databank. For each trial, we applied the eligibility criteria to the community SGLT2i-treated populations. We then assessed the proportion eligible/ineligible for each trial; compared age, sex and comorbidities between trial participants and those eligible/ineligible in routine care; compared rates of serious adverse events in the trials to the expected rate in community SGLT2i-treated participants; and compared the rate of major adverse cardiovascular events (MACE) and mortality between trial and community participants. Results Mean age was similar between trial participants and eligible community-treated participants. The number of comorbidities was consistently lower in trial populations compared people treated in the community. However, compared with other trial populations, participants in the large cardiovascular outcome trials (CANVAS, CANVAS-R, CREDENCE and EMPA-REG) had higher levels of comorbidity and rates of serious adverse event, MACE and mortality that were broadly similar to the expected rate in the community. For the remaining trials, the serious adverse event rate was lower in the trials than the expected rate based on community SGLT2i-treated participants. Conclusion While people with comorbidity are under-represented compared to routine care populations in most trials, the large cardiovascular outcome trials were more representative of SGLT2i-treated patients with similar rates of serious adverse events. While our findings support calls for caution regarding trial representativeness, the criticism that trials are not representative does not apply equally to all trials, some of which closely reflect current drug use.