Amelioration of Albuminuria by Sitagliptin Added to Metformin in Patients with Type 2 Diabetes and Incipient Nephropathy: A Real World Data Study - Abstract
Clinical trials have demonstrated that in patients with type 2 diabetes (T2DM) and albuminuria, dipeptidyl peptidase 4 inhibitors (DPP-4i) are associated with urine albumin-to-creatinine ratio (UACR) reduction. We examined whether a similar effect is observed in clinical practice. Using the electronic medical database of a 2-million-member health organization, we identified 1,248 individuals with T2DM and albuminuria who had sitagliptin added to metformin for a period of at least 120 days. Patients were divided into categories according to baseline UACR: 30-300 mg/g (81%, n=1011) and > 300 mg/g (19%, n=237). All patients had a second UACR obtained following 60 days or more of treatment with sitagliptin. Sitagliptin therapy led to a reduction in HbA1c (-0.69%; -16 mmol/mol p < 0.001) and was significantly associated with a reduction of UACR [median reduction of 31.8% (23.3mg/g) p < 0.001]. In 403 (32.3% of) patients the change in UACR represents a shift to a lower UACR category, while 55 (4.4%) patients shifted to a higher UACR category. Although UACR change was associated with a change in HbA1c (r=0.208, p < 0.001) UACR also significantly decreased for patients without a reduction in HbA1c. In a multivariable model, a baseline UACR of > 300 mg/g Cr in sitagliptin treated patients was associated with an OR of 1.46(95% CI 1.08-1.98) for having a reduction in UACR category compared patients with a UACR of 30-300 mg/g. Males, obese patients, patients with lower eGFR and patients with hypertension were less likely to have a reduction in UACR category. This observational study indicates that sitagliptin added to metformin may decrease UACR in most patients with T2DM and incipient nephropathy in clinical practice, independent of its effect on HbA1c. Whether this represents a glucose-independent DPP-4 mechanism needs further study.