Dapagliflozin, Exenatide Combination Reduces Albuminuria in Type 2 Diabetes

Combined dapagliflozin and exenatide treatment may lower albuminuria among patients with type 2 diabetes (T2D), according to a study published in Diabetes, Obesity and Metabolism.

Researchers included 20 patients (mean age, 70.5 years; 80% men) with both T2D and micro or macroalbuminuria and randomly assigned them to treatment with dapagliflozin (10 mg/ day), exenatide (2 mg/ week), or a combination of both treatments for 6 weeks. Study participants crossed over to another treatment following a 9-week washout period until undergoing all 3 methods of treatment. The primary outcome was the change in urinary albumin-to-creatine ratio (UACR) from baseline, while secondary outcomes included blood pressure, hemoglobin A1c (HbA1c), body weight, extracellular volume, fractional lithium excretion, and renal hemodynamic parameter changes.

Combined dapagliflozin and exenatide treatment and dapagliflozin treatment alone significantly lowered UACR (change from baseline, -26.0% vs -21.9%; P <.001 and P =.003, respectively), but exenatide treatment alone did not result in any significant UACR change from baseline (-7.7%; P =.246).

Combined dapagliflozin and exenatide treatment was also associated with significant decreases in estimated glomerular filtration rate (eGRF; change from baseline, -7.5%; P <.001), HbA1c (change from baseline, -0.6%; P =.003), systolic blood pressure (change from baseline, -10.4%; P =.008), body weight (change from baseline, -10.4%; P =.008), and fat free mass (change from baseline, -3.1%; P =.023), the report shows. Hematocrit levels increased by 1.4% (P =.015).

For the monotherapy treatments, dapagliflozin was associated with decreased eGFR (P =.003) and exenatide was associated with lowered HbA1c levels (P =.015).

A total of 5, 7, and 9 adverse events occurred during dapagliflozin, exenatide, and combined dapagliflozin and exenatide treatments, respectively, in which urinary tract infections were more frequent with dapagliflozin use and gastrointestinal events with exenatide use. A total of 4 serious events occurred — 2 with exenatide treatment and 2 with combined dapagliflozin and exenatide treatment.

Study limitations include a small sample size and short treatment duration.

The researchers concluded that “combining both agents may be an attractive option to reduce the risk of kidney failure in particular given that the mechanism of action of both agents may be different and potentially additive”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.