Sodium-glucose cotransporter-2 inhibitor therapy improves renal and hepatic function in patients with cirrhosis secondary to metabolic dysfunction associated steatotic liver disease and type 2 diabetes

Abstract

Purpose: Metabolic dysfunction-associated steatotic liver disease (MASLD) increases the risk of chronic kidney disease (CKD), compounding morbidity in patients with cirrhosis. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are disease-modifying agents in type 2 diabetes mellitus (T2DM) and CKD, but studies on their use in cirrhosis are limited. We aimed to assess the effect of SGLT2i therapy on renal and hepatic function in patients with Child-Turcotte-Pugh (CTP) B cirrhosis and T2DM.

Methods: We conducted a 48-month longitudinal, retrospective cohort study of 54 patients with CTP B cirrhosis secondary to MASLD and T2DM who were initiated on SGLT2i (n=27) or insulin (n=27). Laboratory data were collected every 3 months. Liver stiffness (LS) was measured every 6 months via transient elastography (TE) and acoustic radiation force impulse with shear wave velocity (ARFI-SWV). The primary outcome was change in glomerular filtration rate (GFR) and chronic kidney disease (CKD) stage. Secondary outcomes included LS changes measured via TE and ARFI. Additional end points included MELD-Na, MELD 3.0, CTP scores, hepatic decompensations, proteinuria, body mass index (BMI), hemoglobin A1c (Hb-A1c), blood glucose (BG).

Results: At baseline, the two groups were comparable in GFR (SGLT2i: 55.6 ± 1.9 vs. insulin: 58.1 ± 2.1 mL/min/1.73 m², p = 0.37), CKD stage, ARFI-SWV (2.9 ± 0.1 vs. 2.8 ± 0.1 m/s, p = 0.26), MELD-Na, and MELD 3.0. The SGLT2i group was older (p < 0.01) and had higher AST (p=0.01), ALT (p<0.01), and CTP scores (p=0.02), but lower LS by TE (p = 0.03). Over 48 months, GFR increased in the SGLT2i group (+13.5 ± 1.3) and declined in the insulin group (-4.2 ± 1.4; p < 0.01). A greater proportion of SGLT2i patients transitioned from CKD stage 3a to 2 (p = 0.04). Liver stiffness by TE decreased in the SGLT2i group (-4.0 ± 1.1 kPa), while it increased in the insulin group (+3.0 ± 2.5 kPa; p < 0.01). ARFI-SWV also declined in the SGLT2i group but increased in the insulin group (2.5 ± 0.1 vs. 3.2 ± 0.1 m/s; p < 0.01). The SGLT2i group also demonstrated significant improvement in MELD-Na, MELD 3.0 and CTP scores, with greater resolution of hepatic decompensations, proteinuria, as well as better BMI and HbA1c outcomes (all p < 0.01).

Conclusions: Patients with CTP B cirrhosis and T2DM receiving SGLT2i therapy experienced a significant improvement in renal, hepatic function, and glycemic control over 48 months compared to patients treated with insulin.

Keywords: Child-Turcotte-Pugh B cirrhosis; chronic kidney disease; glomerular filtration rate; metabolic dysfunction associated steatotic liver disease; sodium-glucose cotransporter-2 inhibitors; type 2 diabetes mellitus.

Figure 1

Representation of GFR changes over time for SGLT2i and insulin groups. Results of independent T test analysis comparing the mean GFR at 6 month intervals for the SGLT2i and insulin groups are provided.

Figure 2

Categorical analysis of chronic kidney disease (CKD) stage progression over time. Patients were stratified by CKD stage (stage 2, stage 3a, and stage 3b) at baseline and at 48 months. Counts and corresponding p-values for between-group comparisons at each time point are shown.

Figure 3

Representation of LS changes over time for SGLT2i and insulin groups. Results of independent T test analysis comparing the mean LS at 6 month intervals for the SGLT2i and insulin groups are provided.

Figure 4

Representation of MELD-Na changes over time for SGLT2i and insulin groups. Results of independent T test analysis comparing the mean MELD-Na at 6 month intervals for the two groups are provided.

Figure 5

Illustration of the changes in CTP class between the start and end of the study for SGLT2i and insulin groups. Counts of CTP class changes over time are reported in the table below.

Figure 6

Illustration of the changes in ascites (a), varices (b), hepatic encephalopathy (c) and proteinuria (d) between start and end of study period. Counts of ascites, varices, hepatic encephalopathy and proteinuria at baseline and end of the study period, as well as new onset and resolution of these conditions are summarized in the table below.