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
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 . 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 . In this analysis, the safety of sitagliptin was compared between participants with CKD and without CKD and between sitagliptin and placebo-treated CKD patients.
- 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).
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.