DPP-4 inhibitor safe for diabetic patients with renal dysfunction
Safety of Sitagliptin in Patients with Type 2 Diabetes and Chronic Kidney Disease: Outcomes from TECOS
Literature - Engel SS, Suryawanshi S, Stevens SR, et al. - Diabetes Obes Metab. 2017; published online ahead of printBackground
Guidelines for the management of type 2 diabetes mellitus (T2DM) recommend the careful balancing of benefits of improved glycaemic control with the risks related to chronic kidney disease (CKD) adverse effects of glucose-lowering medications [1]. DPP-4 inhibitors improve glycaemia in patients with renal insufficiency, including patients on dialysis, and are well-tolerated for up to 1 year, but longer-term data regarding the safety and tolerability of DPP-4 inhibitors are limited [2-4].
The DPP-4 inhibitor sitagliptin, has been evaluated in the TECOS study, which included approximately 3,300 T2DM patients with CKD, and had a median follow-up period of 3 years [5]. In this analysis, the safety of sitagliptin was compared between participants with CKD and without CKD and between sitagliptin and placebo-treated CKD patients.
Main results
- Renal failure events were observed in 3.4% vs. 0.9% of the CKD and non-CKD cohorts respectively, with a modest decrease in mean eGFR over time in the non-CKD but not the CKD cohort.
- Other investigator-reported diabetic complications that occurred more frequently in the CKD cohort included amputation, gangrene, any hospitalisation due to complications of diabetes and infections.
- Severe hypoglycaemia was observed in 3.3% of the CKD cohort vs. 1.7% of the non-CKD cohort (risk difference 1.65, 95% CI 1.04-2.36).
- Bone fractures (3.5% in CKD cohort vs. 2.3%, risk difference 1.20, 95% CI 0.55-1.92) and overall malignancies (4.7% in CKD cohort vs. 3.6%, risk difference 1.11, 95% CI 0.35-1.95) were also more common in the CKD cohort.
- In CKD patients, microalbuminuria was reported in 7.7% of the sitagliptin group and 9.1% of the placebo group, and renal failure in 3.3% and 3.6%, respectively.
- CKD participants assigned to sitagliptin had a marginally lower eGFR during the trial compared with those allocated to placebo (-1.62 mL/min per 1.73 m2, 95% CI -2.37 to -0.87). A similar difference was observed in the per protocol population (-1.70 mL/min per 1.73 m2, 95% CI -2.46 to -0.94).
Conclusion
T2DM patients with CKD in the TECOS study had higher incidences of serious adverse events and diabetic complications compared with non-CKD participants. Compared to placebo, long-term treatment with sitagliptin was well tolerated in CKD participants, with no evidence of adverse impact on the safety endpoints in TECOS.
References
1. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015 Jan;38(1):140-149.
2. Arjona Ferreira JC, Marre M, Barzilai N, et al. Efficacy and safety of sitagliptin versus glipizide in patients with type 2 diabetes and moderate-to-severe chronic renal insufficiency. Diabetes Care. 2013;36(5):1067-1073.
3. Arjona Ferreira JC, Corry D, Mogensen CE, et al. Efficacy and safety of sitagliptin in patients with type 2 diabetes and ESRD receiving dialysis: a 54-week randomized trial. Am J Kidney Dis. 2013;61(4):579-587.
4. Nowicki M, Rychlik I, Haller H, et al. Saxagliptin improves glycaemic control and is well tolerated in patients with type 2 diabetes mellitus and renal impairment. Diabetes Obes Metab. 2011;13(6):523-532.
5. Cornel JH, Bakris GL, Stevens SR, et al. Effect of sitagliptin on kidney function and respective cardiovascular outcomes in type 2 diabetes: outcomes from TECOS. Diabetes Care. 2016;39(12):2304-2310.
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