Document resource
Background Type 2 diabetes (T2D) and viral hepatitis frequently coexist and synergistically worsen liver and non-liver outcomes, yet effective pharmacological strategies remain limited. Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are a novel class of anti-diabetic agents that provide cardiovascular and renal benefits beyond glycemic control. Therefore, we aimed to evaluate hepatic and extrahepatic effectiveness of SGLT-2i through head-to-head comparisons with dipeptidyl peptidase-4 inhibitors (DPP-4i) or glucagon-like peptide-1 receptor agonists (GLP-1RA) among patients with T2D and viral hepatitis in the United States (U.S.).Methods Patients with T2D and viral hepatitis initiating SGLT-2i or comparator drugs (DPP-4i or GLP-1RA) were identified (2007-2022) from the nationwide U.S. Merative™ Marketscan® Research Databases. Primary outcomes included (1) hepatocellular carcinoma (HCC) and cirrhosis, and (2) cardiovascular disease (CVD), chronic kidney disease (CKD), and non-liver cancer. Cox regression models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI).Results After 1:1 propensity score matching, 2,244 patients initiating SGLT-2i vs DPP-4i (mean age 57.5 years, 31.6% female) and 2,506 patients initiating SGLT-2i vs GLP-1RA (mean age 57.8 years, 35.8% female) were included. Compared with DPP-4i, SGLT-2i use was associated with significantly lower risks of any liver-related outcomes (HR 0.74, 95% CI 0.54-0.99, p = 0.049), CVD (HR 0.68, 95% CI 0.47-0.98, p = 0.038), and CKD (HR 0.69, 95% CI 0.49-0.97, p = 0.030; IDDF2026-ABS-0353 Table 1, IDDF2026-ABS-0353 Figure 1. Cumulative incidence of (A) any liver-related outcomes, (B) HCC, (C) cirrhosis, (D) CVD, (E) CKD, (F) non-liver cancer compared SGLT-2i with DPP-4i users in patients with T2D and viral hepatitis). Non-significant trends toward reduced risks were observed for HCC (HR 0.79, 95% CI 0.40-1.57, p = 0.497), cirrhosis (HR 0.76, 95% CI 0.56-1.03, p = 0.074) and non-liver cancer (HR 0.66, 95% CI 0.42-1.04, p = 0.072). In contrast, no significant differences were observed between SGLT-2i and GLP-1RA for any of these outcomes (all p > 0.05; IDDF2026-ABS-0353 Figure 2. Cumulative incidence of (A) any liver-related outcomes, (B) HCC, (C) cirrhosis, (D) CVD, (E) CKD, (F) non-liver cancer compared SGLT-2i with GLP-1RA users in patients with T2D and viral hepatitis). Results were consistent across subgroups stratified by age, sex, and diabetes duration. Sensitivity analyses yielded consistent results with main analyses, including inverse probability of treatment weighting (HRs 0.54-0.97), 6-month landmark analysis (HRs 0.44-0.88) and competing risk models (HRs: 0.60-0.96).Conclusions In this nationwide U.S. cohort study, SGLT-2i was associated with lower risks of liver and non-liver complications compared with DPP-4i, while demonstrating comparable effectiveness to GLP-1RA among patients with T2D and viral hepatitis.Abstract IDDF2026-ABS-0353 Table 1Incidence rates and risk for liver and non-liver outcomes in SGLT-2i vs DPP-4i users, and SGLT-2i vs GLP-1RA users after propensity score matchingCohort 1 (N= 2,244)Cohor 2 (N=2,506)SGLT2iDPP-4iSGLT2iGLP-1RAMedian [IQR] follow-up, years1.25 (0.60-2.45)1.65 (0.82-3.29)1.32 (0.56-2.38)1.39 (0.64-2.64)Any liver-related outcomesNo. of events671127690Incidence rate, per 1,000 PY46.43 (35.98-58.97)58.95 (48.54-70.93)48.59 (38.29-60.82)51.11 (41.10-62.82)Hazard ratio (95% CI)0.74 (0.54-0.99)Ref0.94 (0.69-1.28)RefHCCNo. of events13222116Incidence rate, per 1,000 PY6.53 (3.47-11.16)8.22 (5.15-12.45)9.43 (5.84-14.41)6.34 (3.62-10.29)Hazard ratio (95% CI)0.79 (0.40-1.57)Ref1.46 (0.76-2.80)RefCirrhosisNo. of events701138091Incidence rate, per 1,000 PY48.41 (37.74-61.16059.44 (48.99-71.47)50.99 (40.43-63.46)51.65 (41.58-63.41)Hazard ratio (95% CI)0.76 (0.56-1.03)Ref0.97 (0.72-1.32)RefCVDNo. of events45855575Incidence rate, per 1,000 PY26.49 (19.32-35.44)38.36 (30.64-47.43)28.54 (21.50-37.15)35.60 (28.00-44.62)Hazard ratio (95% CI)0.68 (0.47-0.98)Ref0.80 (0.56-1.13)RefCKDNo. of events531025670Incidence rate, per 1,000 PY31.74 (23.77-41.51)45.72 (37.28-55.50)30.30 (22.89-39.35)34.35 (26.78-43.40)Hazard ratio (95% CI)0.69 (0.49-0.97)Ref0.87 (0.61-1.24)RefNon-liver cancerNo. of events28553240Incidence rate, per 1,000 PY15.05 (10.00-21.75)22.75 (17.14-29.61)15.35 (10.50-21.67)17.28 (12.34-23.53)Hazard ratio (95% CI)0.66 (0.42-1.04)Ref0.86 (0.54-1.37)Ref*Matched for age, sex, smoking, alcohol use disorder, duration of diabetes, diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, HBV treatment, HCV treatment, hyperlipidemia, hypertension, obesity/overweight, COPD, MASLD/MASH, liver cirrhosis, hepatocellular carcinoma, cardiovascular disease, chronic kidney disease, non-liver cancer, CCI, metformin, DPP-4i, CLP-1RA, sulfonylureas, thiazolidinediones, insulin, ACEI/ARB, β-blockers, CCB and statin.Abbreviation: ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CCB, calcium-channel blockers; CCI, Charlson Comorbidity Index; CI, confidence interval; CVD, cardiovascular disease; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; DDP-4i, dipeptidyl peptidase-4 inhibitor; GLP-IRA, glucagon-like peptidase 1 receptor agonist; HBV, hepatitis B virus; HCV, hepatitis C virus; HCC, hepatocellular carcinoma; MASLD, metabolic dysfunction-associated steatotic liver disease; MASH, metabolic dysfunction-associated steatohepatitis; PY, person-years; SGLT-2i, sodium-glucose cotransporter-2 inhibitorAbstract IDDF2026-ABS-0353 Figure 1Abstract IDDF2026-ABS-0353 Figure 2