Exenatide-Dapagliflozin Combo Enhances Kidney Protection: DECREASE Trial

Sodium‐glucose cotransporter‐2 inhibitors and GLP‐1RAs reduce glycated haemoglobin (HbA1c) through distinct yet complementary mechanisms of action. Because of these different mechanisms, combination treatment with SGLT2 inhibitors and GLP‐1RAs may have synergistic effects. However, there are still limited data on the effects of the combined use of SGLT2 inhibitors and GLP‐1RAs on markers of kidney function. Therefore, Dr Charlotte C. van Ruiten MD and his team conducted a study to evaluate the effects of separate and combined use of the SGLT2 inhibitor dapagliflozin and the GLP‐1RA exenatide on measures of kidney function.

It was a prespecified secondary analysis of the DECREASE trial. The researchers included a total of 66 patients and randomly assigned them to 1 of 4 twice-daily oral regimens: dapagliflozin alone, exenatide alone, dapagliflozin and exenatide in combination, or placebo. At week 16 of follow-up, the researchers evaluated kidney function using 24-hour urinary albumin to creatinine ratio (UACR), creatinine and cystatin C‐estimated glomerular filtration rate (GFR) and kidney injury molecule‐1:creatinine ratio (KIM‐1:Cr).

Key findings of the study were:

• By week 16, the researchers found that UACR significantly decreased by

◊ 39% in the dapagliflozin and exenatide group,

◊ 18.1% in the dapagliflozin group,

◊ 15.6% in the exenatide group, and

◊ 11.0% in the placebo group.

• Compared to placebo, they found that the UACR difference at week 16 in the exenatide‐dapagliflozin group was −32.2%.
• They noted similar effects in 37 participants who were using angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers at baseline.
• Compared to placebo, they observed that participants in the exenatide‐dapagliflozin group had an acute dip in estimated GFR with creatinine‐estimated GFR (−4.0 mL/min/1.73 m2) and cystatin C‐estimated GFR (−10.4 mL/min/1.73 m2).
• They noted that the mean KIM‐1:Cr difference in the combined treatment arm versus placebo was −43.8%.

The authors concluded, "In obese patients with type 2 diabetes, combined therapy with exenatide and dapagliflozin may have additive effects on albuminuria, estimated GFR and metabolic risk factors compared to either therapy alone or placebo. These data support dedicated clinical trials to confirm the efficacy and safety of GLP‐1RA/SGLT2 inhibitor combination treatment in improving kidney outcomes."

For further information:

https://doi.org/10.1111/dom.14410