32-PUB: Glycemic Variability after Initiation of SGLT2 Inhibitors in CKD

Background: SGLT2 inhibitors (SGLT2i) are widely used for cardiorenal protection in CKD patients, irrespective of diabetes. While their effect on A1C is smaller with lower eGFR, the impact of SGLT2i initiation on short-term glycemic variability is unclear.

Methods: In a pilot study, we enrolled 11 CKD patients with clinical indications for SGLT2i -7 with type 2 diabetes not on insulin, and 4 without diabetes. Participants wore DexCom G6 CGM for 10 days pre-SGLT2i and another 10 days post-SGLT2i initiation. Linear mixed-effects models with random intercepts were used to analyze glycemic variability, assessed by the hourly coefficient of variation (CV).

Results: The mean age of participants was 68 years, with 82% male, mean eGFR of 38 mL/min/1.73m², and median albuminuria of 347 mg/g. Mean A1C levels were 6.6% in participants with diabetes and 5.5% in those without. Nine participants received empagliflozin 10mg, two dapagliflozin 10mg. Following SGLT2i initiation, participants with diabetes showed no significant change in mean glucose (160±54 vs 155±50 mg/dL, p=0.52), GMI (7.1±1.3 vs 7.0±1.2, p=0.52), or TIR (67±37 vs 69±39%, p=0.66). There was no change in time above range or time below range. Only 1 participant on GLP-1 receptor agonist developed asymptomatic level 1 hypoglycemia. Similarly, patients without diabetes had no change in any of the previously mentioned CGM metrics. However, glycemic variability decreased post-SGLT2i initiation, as shown by hourly CV reductions (-0.40±0.13, p=0.002). The magnitude of hourly CV reduction was more pronounced in participants without diabetes compared to those with diabetes (p-interaction=0.002). Despite higher hourly CV during daytime than nighttime, the impact of SGLT2i initiation on CV was similar across time periods without significant interaction by time of day.

Conclusion: After SGLT2i initiation in CKD, while mean glycemia and TIR remained unchanged, glycemic variability diminished. This finding warrants further investigation in a larger study.