Sodium-glucose link transporter-2 inhibitors in reduced renal function: cross-class comparison from the Association of British Clinical Diabetologists (ABCD) audits

Abstract

Background and aims: The ABCD sodium-glucose link transporter-2 inhibitor (SGLT2i) audits launched with the aim of collecting real-world outcome data in UK practice. Previous work from the individual audits suggests that HbA1c reductions persist at lower eGFR levels but are less than in those with preserved renal function. The aim of this analysis is to assess HbA1c outcomes at reduced eGFR levels across the class and to assess for any differences between drugs. Materials and methods: Data were extracted from the ABCD audits for inclusion; missing data was multiply imputed. Individuals were grouped by baseline renal function using eGFR (mL/min/1.7m2 ) cut-offs as defined in chronic disease staging as follows: group 1 (eGFR≥90); group 2 (eGFR 60-89); group 3 (eGFR <60). Analysis was performed using a multiple linear regression model to correct for change in other covariates with Bonferroni adjustments for between group comparisons. Results: Data for 21,338 individuals were included (Empagliflozin=11,234; Dapagliflozin=7,841; Canagliflozin=2,263) with mean±SD age 60.0±10.4years; HbA1c 75.8±2.53mmol/mol; BMI 33.9±7.1kg/m2 ; weight 97.5±22.1kg and eGFR 81.6±13.3mL/min/1.73m2 . Median duration of diabetes 8.1 years (IQR 4.2-12.3). 61.2% were male. The median duration of follow-up across the population was 1.7 years (IQR 0.9-2.8). HbA1c fell by 9.8mmol/mol (95% CI 9.5-10.1, p<0.0001) across the entire population. Including all levels of renal function, empagliflozin was associated with larger reductions in HbA1c than dapagliflozin (10.4mmol/mol [95% CI 10.0-10.7] vs. 9.0mmol/mol [95% CI 8.5-9.5]; p-value between drugs <0.0001) but no other differences between SGLT2i drugs were noted. Group 1 findings mirrored this with HbA1c reduction of 11.4mmol/mol (95% CI 10.9-11.9) with empagliflozin vs. 9.9mmol/mol (95% CI 9.3-10.5) with dapagliflozin (p <0.0001) and no difference was noted between any other drug comparisons. In groups 2 and 3 no difference in HbA1c reductions was noted between drugs. Within each drug group, and across the entire population, there was a trend towards smaller HbA1c reductions in those in group 2 and 3 but failing to reach statistical significance (p>0.3 for all). Conclusion: In those with preserved renal function (eGFR>90) empagliflozin may have greater glycaemic efficacy than dapagliflozin. No difference in glucose outcomes between the drugs was noted at lower eGFR levels. Interestingly, in this analysis the difference in HbA1c reductions at with lower eGFR failed to reach statistical significance but a trend toward attenuated glucose lowering effects was noted.