Urinary Albumin Secretion in Type 2 Diabetes Patients (T2DM) With Albuminuria Treated With Sitagliptin as Add-on Therapy to Metformin: A Real World Data Study

Reduction in Urine Albumin-to-Creatinine Ratio (UACR) by dipeptidyl peptidase 4 inhibitor (DPP-4i) therapy was documented in clinical trials in T2DM patients with albuminuria. To examine whether a similar effect occurs in the real world, we analyzed a large Israeli HMO database. We identified 1,248 eligible T2DM patients with albuminuria who had sitagliptin added to their metformin therapy for at least 120 days. Baseline UACR, taken 4 months before sitagliptin initiation, was divided to three categories: 30-100 mg/gr found in 54.3% (n=643), 100-300 mg/g in 26.3% (n= 28) and >300 mg/g in 19% (n=237). All patients had a second UACR after >60 days on sitagliptin and an eGFR >45 ml/min. A total of 523 (41.9%) patients moved to a lower UACR category at follow-up and 561 (45%) stayed at the same baseline UACR category, while 164 patients (13.1%) shifted to a higher UACR category. 58% (n=658) experienced a reduction of over 20% of baseline UACR. HbA1c levels were reduced by 0.69% (P<0.001). UACR was significantly (P<0.01) improved even for patients with no reduction in HbA1c. In a multivariable model, being in the highest baseline UACR category was associated with an odds ratio of 3.88 (95% CI: 2.40-6.25) for having at least 20% UACR reduction compared with being in the lowest category. Males and obese patients were significantly less likely to achieve a 20% reduction in their UACR level. Changes in UACR were associated with changes in HbA1c (r=0.208, p<0.001) but not with baseline HbA1c. In conclusion, a majority of T2DM patients with micro- and macroalbuminuria treated with sitagliptin as add-on therapy to metformin experienced a reduction in urinary albumin excretion. The magnitude of improvement in UACR was related to HbA1c reduction; however, reduction in UACR was significant even when there was no reduction in HbA1c levels. Whether this represents a glucose independent, DPP-4-dependent mechanism of albuminuria reduction needs further study.