(B-189) Representativeness of Vulnerable Populations in Randomized Controlled Trials Evaluating the Efficacy and Safety of SGLT-2 Inhibitors: A Systematic Review and Meta-analysis

Background: Randomized controlled trials (RCTs) have shown that sodium-glucose cotransporter 2 (SGLT-2) inhibitors benefit patients with type 2 diabetes, heart failure, and chronic kidney disease. However, vulnerable populations—children, older adults, women, racial and ethnic minorities, and patients with chronic kidney or liver disease— may be underrepresented in these trials, which may pose a challenge to the generalizability of the findings, especially for those who bear a disproportionate burden of these conditions.

Objectives: We conducted a systematic review and meta-analysis to assess the pooled prevalence of the vulnerable populations in SGLT-2 inhibitor RCTs across different indications and to identify factors influencing their inclusion in these trials.

Methods: We systematically searched Cochrane Central Register of Controlled Trials, Medline, and Embase to identify all relevant studies until January 8, 2025. Studies published phase 3 or 4 RCTs (300 participants or more) assessing the efficacy and safety of SGLT-2 inhibitors and reported the number of participants in any vulnerable population group were included. We calculated the pooled prevalence with the 95 % confidence interval of each vulnerable population in included SGLT-2 trials using a random-effects model. Heterogeneity was measured across studies using I2 and tau² and explored using subgroup analyses and random-effects meta-regression. The subgroup characteristics were pre-specified and selected based on their clinical and epidemiological relevance.

Results: In 91 included RCTs, the pooled prevalence was 42.1% for females (95% confidence interval 40.2% to 44.1%, 55,751 participants), 42.3% for older adults (95% CI 36.4% to 48.2%, 33,113 participants, 28 RCTs), 33.7% for patients with chronic kidney disease (CKD) (95% CI 20.9% to 47.9%, 35,716 participants, 37 RCTs), 4.8% for Black participants (95% CI 4.2% to 5.4%, 5,227 participants, 72 RCTs), 17.2% for Asians (95% CI 13.5% to 21.3%, 21,547 participants, 75 RCTs), 1.7% for Indigenous participants (95% CI 0.7% to 3.1%, 862 participants, 19 RCTs), and 20.0% for Hispanic or Latino participants (95% CI 13.4% to 27.6%, 3,991 participants, 16 RCTs). Data for liver disease and participants under 18 were insufficient. The study population, number of trial centers, and enrollment continent may significantly influence the inclusion of these vulnerable populations.

Conclusions: The findings revealed that vulnerable populations were underrepresented in SGLT-2 inhibitor RCTs, which could impact the generalizability of study results. Efforts should be made to improve the inclusion of these groups in future RCTs to ensure broader applicability of findings.