Association of Renal and Cardiovascular Safety With DPP‐4 Inhibitors vs. Sulfonylureas in Patients With Type 2 Diabetes and Advanced Chronic Kidney Disease

Abstract

This study assessed the effects of dipeptidyl peptidase-4 inhibitors (DPP4is) vs. sulfonylureas (SUs) on composite renal, cardiovascular, and hospitalized hypoglycemia outcomes in type 2 diabetes (T2D) patients with advanced chronic kidney disease (CKD) who were underrepresented in previous clinical studies. The National Health Insurance Research Database was utilized. Patients with T2D and advanced CKD (stages 3b-5) with stable use of DPP4is or SUs were identified during 2011-2015 and followed until death or December 31, 2016. The primary outcome was the composite renal outcome. Secondary outcomes included hospitalized heart failure (HHF), major adverse cardiovascular event (MACE), hospitalized hypoglycemia, and all-cause death. Subdistribution hazard models were employed to assess treatment effects on clinical outcomes. A total of 1,204 matched pairs of DPP4i and SU users were analyzed. Compared with SUs, DPP4is had no significant difference in the risks of the composite renal outcome, HHF, and three-point and four-point MACE (hazard ratios (95% confidence intervals): 1.10 (0.93-1.31), 1.11 (0.95-1.30), 0.97 (0.79-1.19), and 1.08 (0.94-1.24), respectively), but reduced risks of hospitalized hypoglycemia (0.53 (0.43-0.64)) and all-cause death (0.71 (0.53-0.96)). In conclusion, among patients with T2D and advanced CKD, the use of DPP4is vs. SUs was associated with comparable safety profiles on renal and cardiovascular outcomes, and reduced risks of hospitalized hypoglycemia and all-cause death. DPP4is may be preferred for patients with T2D and advanced CKD, and the regular monitoring on cardiac function remains crucial among this population who are at a higher risk of HHF.

Cardiovascular Benefits With Favorable Renal, Amputation and Hypoglycemic Outcomes of SGLT-2 Inhibitors in Type 2 Diabetes From the Asian Perspective: A Population-Based Cohort Study and Systematic Review

“…The PS for each patient was estimated using a logistic regression model where drug exposure (SGLT2is versus DPP4is) was treated as the dependent variable, and a series of patient characteristics, including demographics at the index date, diabetes-related complications in the year prior to the index date, and previous exposure to GLAs and CVD-related medications in the year prior to the index date, were measured as the independent variables. Additionally, to minimize the potential heterogeneity in baseline patient renal function, several surrogate indicators from previous studies ( 25 ) and recommendations of clinical experts were measured and included in the estimation of PS. These indicators were the status of participation in a pay-for-performance program for pre-end-stage renal disease (ESRD) at the index date, which was a proxy for patients with an estimated glomerular filtration rate (eGFR) level of less than 45 ml/min/1.73 m 2 , and exposure to metformin, acarbose, or sulfonylureas within 90 days prior to the index date, which were proxies for patients with eGFR levels of less than 30, 25, and 15 ml/min/1.73 m 2 , respectively.…”

Role of dipeptidyl peptidase 4 inhibitors in the new era of antidiabetic treatment

“…The relatively long half-lives of sitagliptin, linagliptin and alogliptin allow for once-daily dosing. Saxagliptin, which has a short half life, may also be administered once daily due to the presence of its active metabolite, BMS-510849, which inhibits DPP-4[ 35 - 37 ]. In contrast, vildagliptin has a short half-life and, thus, requires twice-daily dosing[ 38 ].…”

“…Experimental data suggest that the modulation of innate immunity and inflammation are probably involved in these kidney-protective effects. The degradation of DPP-4, which is known to be expressed on the cell membrane of many types of cells including immune cells, as well as of several chemokines and cytokines[ 36 ], the attenuation of oxidative stress, fibrosis and cellular apoptosis in the kidney[ 37 ] are plausible underlying mechanisms.…”

Trends in baseline HbA1c and body-mass index in randomised placebo-controlled trials of type 2 diabetes from 1987 to 2022: a systematic review and meta-analysis

“…It was supposed that the study design for DPP-4is were becoming more focused on its hypoglycemic effects and cardiovascular safety rather than weight loss. 52 , 53 Therefore, the BMI criteria for DPP-4i trials might become relatively lower, showing a declining trend. Likewise, SGLT-2is gained extensive attention in recent years for their excellent cardiovascular and renal benefits.…”