Background: The association between sodium glucose cotransporter 2 inhibitors (SGLT2I) versus dipeptidyl peptidase-4 inhibitors (DPP4I) and the risks of non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) are currently unknown. Methods: This was a retrospective population-based cohort study including type-2 diabetes mellitus (T2DM) patients treated with either SGLT2I or DPP4I between 1st January 2015 and 31st December 2019 in Hong Kong. Patients with concurrent DPP4I and SGLT2I usage were excluded. The primary outcomes were NAFLD and HCC. The secondary outcomes included cancer-related mortality and all-cause mortality. Propensity score matching (1:1 ratio) was performed using the nearest neighbour search. Univariable and multivariable Cox regression was applied to identify significant predictors. Competing risks models and multiple approaches using the propensity score were performed. Results: This cohort included 62699 patients with T2DM, amongst which 22154 patients were on SGLT2I and 40545 patients were on DPP4I. After matching (44308 patients), 1090 patients developed new-onset NAFLD (Incidence: 4.6; 95% Confidence interval [CI]: 4.3-4.9) and 187 patients developed HCC (Incidence: 0.8; 95% CI: 0.7-0.9). Overall, SGLT2I was associated with lower risks of NAFLD (Hazard ratio [HR]: 0.39; 95% CI: 0.34-0.46), and HCC (HR: 0.46; 95% CI: 0.29-0.72) compared to DPP4I after adjustments. SGLT2I was also associated with lower risks of cancer-related mortality (HR: 0.29; 95% CI: 0.23-0.37) and all-cause mortality (HR: 0.28; 95% CI: 0.25-0.31). However, amongst patients with hepatitis B virus infection, SGLT2I was associated with higher risks of HCC (HR: 3.28; 95% CI: 1.21-8.90). The results were consistent in competing risk models and different matching approaches. Conclusion: SGLT2I was associated with lower risks of NAFLD, and HCC compared to DPP4I after propensity scores matching and adjustments.

Background and Aims Metformin is an oral anti‐hyperglycemic recommended by the American Diabetes Association (ADA) as a preferred initial pharmacologic agent for type 2 diabetes. Metabolic acidosis is a rare yet severe side effect of it. We examined the association of metformin use and dosage on the risk of metabolic acidosis in diabetic patients with different degrees of chronic hepatitis B (CHB)‐related cirrhosis and chronic kidney disease (CKD). Methods Metabolic acidosis was defined by blood pH ≤7.35, together with lactate >5 mmol/L or arterial bicarbonate ≤18 mmol/L or venous bicarbonate ≤21 mmol/L, and/or diagnosis codes. Child‐Pugh class and CKD stage were included in the model as time‐dependent covariates. Age, gender, comorbidities, and use of relevant medications were adjusted as covariates. Maximum daily dose of metformin was classified into ≤1000 mg and >1000 mg. Results We identified 4431 diabetic patients with CHB‐related cirrhosis between 2000 and 2017 from a territory‐wide database in Hong Kong. The risk of metabolic acidosis increased with Child‐Pugh class B and C cirrhosis regardless of CKD stage (adjusted subdistribution hazard ratio [aSHR] ranged from 3.50 to 86.16). Metformin use was associated with a higher risk in patients with Child‐Pugh class B or C cirrhosis and stage 3A CKD or above (aSHR ranged from 1.55 to 2.46). In stage 4/5 CKD, a daily dose of metformin ≤1000 mg was still associated with a higher risk of metabolic acidosis regardless of the severity of cirrhosis (aSHR ranged from 2.45 to 3.92). Conclusion In conclusion, patients with Child‐Pugh class B cirrhosis or above were at a higher risk of metabolic acidosis. Metformin further increased the risk in patients with Child‐Pugh class B cirrhosis or above and stage 3A CKD or above. Dose adjustment in stage 4/5 CKD did not reduce the risk of metabolic acidosis.

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Background & Aim Diabetes mellitus is associated with the development of pancreatic cancer, but few large-scale studies have examined its predictive risk factors. The present study aims to examine the predictors for PaC in patients with type 2 diabetes mellitus in a territory-wide retrospective cohort study. Methods This was a territory-wide retrospective cohort study of patients with type 2 diabetes mellitus over the age of 40 and no prior history of pancreatic cancer. Baseline demographics, use of anti-diabetic medications, comorbidities and biochemical parameters were extracted. Cox regression was used to calculate hazard ratios (HR) with 95% confidence intervals (CI). Subgroup analyses based on chronic kidney disease stages were performed. Results This study consisted of 273738 patients (age = 65.4 ± 12.7 years old, male = 48.2%, follow-up duration = 3547 ± 1207 days, disease duration = 4.8 ± 2.3 years), amongst which 1148 developed pancreatic cancer. The number of anti-diabetic medications prescribed (HR: 1.20; 95% CI: 1.01-1.42; P = 0.040), diabetic microvascular complications (HR: 1.91; 95% CI: 1.30-2.81; P < 0.001), chronic kidney disease (HR: 1.81; 95% CI: 1.25-2.64; P = 0.002), use of acarbose (HR: 2.24; 95% CI: 1.35-3.74; P = 0.002) and use of glucagon-like peptide-1 receptor agonist (HR: 4.00; 95% CI: 1.28-12.53, P = 0.017) were associated with pancreatic cancer development on multivariable Cox regression adjusting for the duration of diabetes mellitus, mean HbA1c, and history of pancreatic diseases. Stage 3A chronic kidney disease or below was associated with pancreatic cancer but not stage 3B or beyond. Conclusion Diabetic microvascular complications, especially stage 1, 2 and 3A chronic kidney disease, were associated with pancreatic cancers.

Background: Diabetes mellitus is associated with the development of colorectal cancer (CRC). There have been a lack of study comparing the risk of colorectal cancer in sodium-glucose co-transporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase 4 inhibitors (DPP4i), both of which commonly prescribed second line agents for diabetes. Methods: We conducted a territory wide retrospective cohort study on patients with type 2 diabetes who was prescribed either of the two agents. Baseline demographics, use of other medications, comorbidities and biochemical parameters were extracted. Propensity score matching was performed to reduce the impacts of cofounders. Cause specific Cox regression was used to evaluate the risk of incident colorectal cancer in SGLT2i users, as compared to DPP4i users. Subgroup analyses based on age, gender and estimated glomerular filtration rate were performed. Results: After propensity score matching, we included 13029 subjects who were prescribed SGLT2i and DPP4i respectively. Incidence rate ratio of CRC was 0.566 (0.418-0.766) in SGLT2i users. Overall, use of SGLT2i was associated with a lower risk of incident CRC (HR: 0.526; 95% CI: 0.382-0.724; P <0.001). In subgroup analyses, use of SGLT2i was associated with lower risks of incident CRC only in men (HR: 0.461; 95% CI: 0.303-0.702; P <0.001), patients < 65 years old and patients (HR:0.294; 95% CI: 0.174-0.496; P<0.001) with eGFR ≥ 45 mL/min/ 1.73m2 (HR: 0.560; 95% CI: 0.395-0.792; P =0.001). Conclusion: Use of SGLT2i may reduce risk of incident CRC as compared to use of DPP4i, especially in younger male patients with fairly preserved renal function.