Dapagliflozin–saxagliptin ‘attractive’ options for patients with type 2 diabetes with chronic kidney disease

MedwireNews (April 16, 2019): Dapagliflozin, with or without saxagliptin, reduces albuminuria in people with type 2 diabetes and moderate-to-severe chronic kidney disease when used in combination with antihypertensive treatments, DELIGHT study data show. Furthermore, using the sodium-glucose co-transporter (SGLT)2 inhibitor and dipeptidyl peptidase-4 inhibitor together achieved “the dual objectives of effective lowering of blood glucose and reduction of urinary albumin excretion,” Hiddo Heerspink (University of Groningen, the Netherlands) and co-authors write in The Lancet Diabetes & Endocrinology.

They add: “This beneficial profile makes the combination of these drugs a potentially attractive option to slow the progression of kidney and cardiovascular disease in these patients.”

The phase III DELIGHT study included 448 patients with type 2 diabetes and moderate-to-severe chronic kidney disease who were randomly assigned to 24 weeks of once-daily treatment with dapagliflozin 10 mg (n=145), dapagliflozin 10 mg plus saxagliptin 2.5 mg (n=155), or placebo (n=148).  At baseline, median urine albumin-to-creatinine ratio (UACR) ranged from 218.4 to 270.0 mg/g, mean estimated glomerular filtration rate (eGFR) was 47.7–50.2 mL/min per 1.73 m2, and mean glycated hemoglobin (HbA1c) was 8.2–8.6% (66.0–70.0 mmol/mol).  By week 24, UACR was a significant 21% lower in the dapagliflozin group than in the placebo group, and it was  a significant 38% lower  in the dapagliflozin–saxagliptin group. The researchers note that the reductions were “largely independent” of simultaneous changes in HbA1c, systolic blood pressure, eGFR, and uric acid.

Heerspink and team also found that HbA1c was a signficant 0.58% lower in the dapagliflozin–saxagliptin group than in the placebo group at week 24, and was a non-significant 0.16% lower in the dapagliflozin-only group.

They say: “The reduction in HbA1c when saxagliptin is added to dapagliflozin is clinically relevant in patients with kidney impairment because the glycaemic effects of SGLT2 inhibitors are attenuated when kidney function declines.” Both drugs were well tolerated by patients with no new safety signals observed.

In accompanying commentary, Katherine Tuttle (University of Washington, Spokane, USA) stresses the importance of the finding “that dapagliflozin and saxagliptin can be used together safely for glycaemic control in patients with type 2 diabetes and moderate- to severe chronic kidney disease.”

She writes: “Because there are few drugs available to treat hyperglycaemia without increasing risk of hypoglycaemia (and other adverse events) for this population, the current data provide reassurance about combining SGLT2 inhibition with an incretin mimetic.”

Heerspink et al conclude that the DELIGHT data “support the importance of SGLT2 inhibitors in reducing albuminuria in patients with type 2 diabetes and chronic kidney disease when used in addition to guideline­recommended treatment.”  However, they add: “Whether or not this effect translates into improved kidney outcomes remains uncertain and requires dedicated outcome trials with longer follow-up.”

Written by Laura Cowen and reproduced from MedwireNews

medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group

References:

Lancet Diabetes Endocrinol 2019; doi:10.1016/S2213-8587(19)30086-5
Lancet Diabetes Endocrinol 2019; doi:10.1016/S2213-8587(19)30116-0

Additional information on diabetic nephropathy can be found here.

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