Comparison of Abbreviated Modification of Diet in Renal Disease Formula (aMDRD) and the Cockroft-Gault Adjusted for Body Surface (aCG) Equations in Stable Renal Transplant Patients and Living Kidney Donors

Ning

Chan

et al. 2022

Preprint

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.

Section: Methodsmentioning

confidence: 99%

Lower risks of sodium glucose cotransporter 2 (SGLT2) inhibitors compared to dipeptidyl peptidase-4 (DPP4) inhibitors for new-onset non-alcoholic fatty liver disease and hepatocellular carcinoma in type 2 diabetes mellitus: A population-based study

Ning

Chan

et al. 2022

Preprint

“…The baseline laboratory examinations, including the complete blood count, renal and liver biochemical tests, and the lipid and glucose profiles were extracted. The renal function was calculated using the abbreviated modification of diet in renal disease (MDRD) formula (20).…”

Section: Methodsmentioning

confidence: 99%

Lower risks of new-onset acute pancreatitis and pancreatic cancer in sodium glucose cotransporter 2 (SGLT2) inhibitors compared to dipeptidyl peptidase-4 (DPP4) inhibitors: a propensity score-matched study with competing risk analysis

Zhou

Mui³

et al. 2022

Preprint

Background: Dipeptidyl peptidase-4 inhibitors (DPP4I) may be associated with higher risks of acute pancreatitis and pancreatic cancer. This study compared the risks of acute pancreatitis and pancreatic cancer between sodium glucose cotransporter 2 inhibitors (SGLT2I) and DPP4I users. Methods: This was a retrospective population-based cohort study of patients with type-2 diabetes mellitus on either SGLT2I or DPP4I between January 1st 2015 and December 31st 2020 in Hong Kong. The primary outcome was new-onset acute pancreatitis and pancreatic cancer. Propensity score matching (1:1 ratio) using the nearest neighbour search was performed. Univariable and multivariable Cox regressions were applied to identify significant predictors. Results: This cohort included 31609 T2DM patients (median age: 67.4 years old [SD: 12.5]; 53.36% males). 6479 patients (20.49%) used SGLT2I, and 25130 patients (70.50%) used DPP4I. After matching, the incidence of acute pancreatitis was significantly lower in SGLT2I users (incidence rate, IR: 0.6; 95% confidence interval, CI: 0.2-1.4) than in DPP4I (IR: 2.1; CI: 1.3-3.0). The incidence of pancreatic cancer was also lower among SGLT2I users (IR: 1.4; 95% CI: 0.7-2.6 vs. 3.6; 95% CI: 2.6- 4.9). SGLT2I was associated with lower risks of acute pancreatitis (hazard ratio, HR: 0.11; 95% CI: 0.02-0.51; P=0.0017) and pancreatic cancer (HR: 0.22; 95% CI: 0.039-0.378; P=0.0003) after adjustments. The results were consistent in the competing risk models and the different matching approaches. Conclusions: SGLT2I may be associated with lower risks of new-onset acute pancreatitis and pancreatic cancer after matching and adjustments, underscoring the need for further evaluation in the prospective setting.

“…Baseline biochemistry, including the complete blood count, renal function tests, liver function tests, lipid and glycemic profiles were extracted. Estimated glomerular filtration rate (eGFR) was calculated by the abbreviated modification of diet in renal disease (MDRD) formula 27 .…”

Section: Study Design and Populationmentioning

confidence: 99%

Lower Risks of Incident Colorectal Cancer in SGLT2i Users Compared to DPP4i Users: A Propensity Score-matched Study with Competing Risk Analysis

Chan

et al. 2022

Preprint

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.