Patients With T2D, Mild Renal Impairment Can Benefit From A DPP-4 Inhibitor

A new study compared the efficacy and safety of sitagliptin with dapagliflozin in patients with both type 2 diabetes and mild renal impairment. Sitagliptin showed greater glycemic efficacy over dapagliflozin when added onto existing therapy.

Included in the 24-week study were 613 patients with HbA1c 7.0-9.5% and eGFR 60-<90 ml/min/1.73m2 taking metformin ± sulfonylurea. Eligible participants were randomized into one of two groups, the first of which included patients taking sitagliptin 100 mg once daily and the other group taking dapagliflozin 5 mg titrated up to 10 mg once daily (n=307 and n=306, respectively).

A longitudinal data analysis model was used to test whether sitagliptin showed non-inferiority to dapagliflozin in reducing HbA1c at 24 weeks. Primary endpoints included fasting plasma blood glucose, 2-hour post-prandial blood glucose, post-prandial insulin and glucagon, insulin-to-glucagon ratio, and the change in baseline in HbA1c at 24 weeks. Baseline mean HbA1c was 7.7% and 7.8%, and mean eGFR was 79.4 ml/min/1.73m2 and 76.9 ml/min/1.73m2 for the sitagliptin and dapagliflozin groups, respectively.

At 24 weeks, the sitagliptin group showed a greater mean change in HbA1c from baseline vs. the dapagliflozin group (between-group difference, -0.15% [95% CI, -0.26 to -0.04] p=0.006). These results confirmed both the non-inferiority and superiority of sitagliptin over dapagliflozin in mean reduction of HbA1c, meeting the prespecified criteria.

Investigators also observed a greater percentage of patients reaching goal HbA1c of <7% in the sitagliptin group, with 43% of patients reaching HbA1c goal in the sitagliptin group vs. only 27% reaching HbA1c goal in the dapagliflozin group (between-group difference, 15.5 [95% CI, 7.7-23.2]). No significant between-group difference was noted for the 2-hour post-prandial glucose excursion.

In addition to greater control of glycemic, the sitagliptin group also displayed a lower number of adverse events, with only 48.9% of participants experiencing one or more adverse events compared with 51.6% in the dapagliflozin group.

Overall, investigators gave compelling evidence for the addition of sitagliptin therapy in patients with type 2 diabetes and mild renal insufficiency whose glucose levels were inadequately controlled on metformin ± sulfonylurea. Compared with dapagliflozin, sitagliptin proved to be more advantageous in regards to not only glycemic efficacy, but also safety and tolerability. As the number of patients with type 2 diabetes and comorbid conditions continues to rise, further studies are needed to better serve clinicians when evaluating therapy for their patients.

Practice Pearls:

• In patients with type 2 diabetes and mild renal insufficiency who are inadequately controlled on metformin with or without sulfonylurea therapy, sitagliptin may be added to reach glycemic goals.
• Compared to dapagliflozin, sitagliptin displays a better safety profile in addition to a greater reduction in HbA1c.
• Neither dapagliflozin nor sitagliptin has a significant effect on 2-hour post-prandial glucose levels when added to metformin ± sulfonylurea in patients with type 2 diabetes and mild renal insufficiency.
• Further studies are needed to compare additional DPP-4 inhibitors and SGLT2 inhibitors in their safety and efficacy in patients with type 2 diabetes and mild renal insufficiency.

References:

Scott, R., Morgan, J., Zimmer, Z., Lam, R.L., O’Neill, E.A., Kaufman, K.D., Engel, S.S. and Raji, A. (2018), A Randomized Clinical Trial of the Efficacy and Safety of Sitagliptin Compared with Dapagliflozin in Patients with Type 2 Diabetes Mellitus and Mild Renal Insufficiency: The CompoSIT‐R Study. Diabetes Obes Metab. Accepted Author Manuscript. doi:10.1111/dom.13473

“Sitagliptin Improves Glycemic Profile in Type 2 Diabetes, Mild Renal Impairment.” Healio, SLACK Incorporated, 1 Aug. 2018, www.healio.com/endocrinology/diabetes/news/in-the-journals/{4f2b09f9-38da-4332-b127-efb38998494e}/sitagliptin-improves-glycemic-profile-in-type-2-diabetes-mild-renal-impairment.

Clarke Powell, Pharm.D. Candidate 2019, LECOM School of Pharmacy