Therapeutic options are limited for type 2 diabetics with severe renal insufficiency due to contraindications and/or risk of hypoglycemia. Dipeptidyl peptidase-4 (DPP4) inhibitors are approved for use in this patient population; however, there is limited data directly comparing the safety and efficacy between these agents.
All DPP-4 inhibitors prolong meal-induced increases in GLP1 and GIP for several hours in order to decrease the rate of GLP1 and GIP inactivation. The mechanism of action and low risk of hypoglycemia associated with DPP-4 inhibitors make them an appealing option for difficult-to-treat patients. Since differences in binding kinetics exist within the class of DPP-4 inhibitors, a study was conducted to compare the safety and efficacy of vildagliptin and sitagliptin in type 2 diabetics who suffer from severe renal impairment.
The study was a parallel-arm, randomized, multicenter, double blind, 24-week study conducted in 87 centers across Brazil and the USA. Researchers randomized a total of 148 patients, and divided 83 to vildagliptin treatment group and 65 to sitagliptin treatment group. Patients included were diagnosed with type 2 diabetes and were either drug naïve or currently being treated with anti-diabetic agents. Baseline HbA1C were between 6.5% to 10% and an estimated GFR of less than 30 mL/min. Patients received recommended doses of either 50 mg vildagliptin once daily or sitagliptin 25 mg once daily. Parameters to measure efficacy were changes in HbA1C and fasting plasma. Parameters to measure safety were assessment of treatment-emergent adverse events.
In the study analysis after 24 weeks, the adjusted mean difference in HbA1C for vildagliptin was -0.54% (5.9 mmol/mol) from a baseline of 7.52% (59 mmol/mol). The results for sitagliptin was -0.56% (6.1 mmol/mol) from a baseline of 7.80% (62 mmol/mol). There was no statistical significance recognized with this difference (p=0.185). HbA1C and FPG were measured at all visits, and safety parameters were recorded and evaluated by the investigator. Both drugs studied displayed similar safety profiles. The drugs were well-tolerated; however, it is important to note that these patients had multiple concomitant medical conditions, where nearly all patients also received antihypertensive, lipid-lowering, and platelet inhibitor agents. Therefore, although unlikely, the safety profile specific to anti-diabetics may not have been as accurate.
The authors conclude that this is the first study performed to directly compare the safety and efficacy of vildagliptin and sitagliptin. In addition, it is recognized that both of these agents have a similar propensity of lowering HbA1C with relatively well-tolerated adverse event profiles.
- At recommended doses for maximal effectiveness, both vildagliptin and sitagliptin show similar efficacy and safety in treating type 2 diabetics with severe renal impairment
- The percentage of patients achieving an HbA1C target of ≤ 6.5% was higher in vildagliptin treated group compared to sitagliptin.
- It is important to note that majority of patients studied were treated with insulin; therefore, insulin likely diminishes any differences observed with prolonging effects of GLP1 with vildagliptin during the overnight period.
doi: 10.2337/dc06-0706 Diabetes Care December 2006 vol. 29 no. 12 2638-2643