Dapagliflozin and renal function. Re: Diabetes and kidney disease: the role of sodium–glucose cotransporter-2 (SGLT-2) and SGLT-2 inhibitors in modifying disease outcomes. Mende CW. Curr Med Res Opin 2017;33:541-551

Dear Editor,

We read with interest the recently published review published by Mende entitled “Diabetes and kidney disease: the role of sodium–glucose cotransporter-2 (SGLT-2) and SGLT-2 inhibitors in modifying disease outcomes”¹. It is of interest that there are isolated incidents of deterioration in renal function associated with the use of SGLT-2 inhibitors in clinical trials^2,3. We agree with Mende and other publications⁴ providing experimental evidence that SGLT-2 inhibitors are nephroprotective rather than nephrotoxic.

We have examined changes in renal function in our routine real-world clinic practice database before and during treatment with dapagliflozin. Dapagliflozin is recommended by NICE as monotherapy or in combination with other anti-diabetic medications including insulin in type 2 diabetes⁵. In our practice, dapagliflozin was added to concomitant anti-diabetic medications including insulin and GLP-1 agonists. We undertook a prospective audit of patients who had been initiated on dapagliflozin and had undergone at least one follow-up visit. A paired t-test was performed to examine changes in serum creatinine and estimated glomerular filtration rate (eGFR) before and during treatment with dapagliflozin. We identified 148 patients (63% male) with a mean age of 57.8 ± 9.0 years who had received a mean duration of treatment of 15.6 ± 8.7 months with dapagliflozin. We observed no significant changes in pre- and post-treatment serum creatinine (76 ± 18 vs. 77 ± 21 μmol/L, p = .509) or eGFR (92 ± 23 vs. 92 ± 24 mL/min per 1.73 m², p = .983). A modest but significant reduction in systolic blood pressure (139 ± 19 vs. 134 ± 19 mmHg, p = .002) and diastolic blood pressure (79 ± 10 vs. 77 ± 8 mmHg, p = .025) was observed. Significant reduction in HbA1c, body weight and body mass index (BMI) were also observed as shown in Table 1. In those individuals with a follow-up of less than 6 months (n = 23), eGFR decreased from 87 ± 20 to 80 ± 20 mL/min per 1.73 m², p = .02).

Table 1. Mean change in renal function, blood pressure, HbA1c and body weight in patients receiving dapagliflozin.

Measurement	Baseline	Follow-up	Mean difference (95% CI)	p
Creatinine (μmol/L)	76 ± 18	77 ± 21	1 (−2, 4)	.509
eGFR (mL/min per 1.73 m^2)	92 ± 23	92 ± 24	0 (−3, 3)	.983
Weight (kg)	105 ± 18	102 ± 18	−3 (−4, −2)	<.001
BMI (kg/m^2)	36 ± 6	35 ± 6	−1 (−1.4, −0.8)	<.001
SBP (mmHg)	139 ± 19	134 ± 19	−5 (−8, −2)	.002
DBP (mmHg)	79 ± 10	77 ± 8	−2 (−4, 0.2)	.025
HbA1c (mmol/mol)	82 ± 18	69 ± 13	−13 (−16, −10)	<.001

Unless indicated otherwise, data given as mean ± SD.

Abbreviations. eGFR, estimated glomerular filtration rate; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; CI, confidence interval.

In conclusion, no significant change in renal function was observed in our cohort (n = 148), who had been treated with dapagliflozin for a mean duration of 15.6 months. Our finding supported the idea that SGLT2 inhibitors are not nephrotoxic. Larger studies with long-term follow-up are warranted to confirm the nephroprotective effect of SGLT2 inhibitors.

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Declaration of funding

This letter was not funded.

Declaration of financial/other relationships

J.W.S. has disclosed that he has received a research grant from AstraZeneca. T.M., L.W., D.M.W., E.P. and A.G. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

Acknowledgments

We acknowledge the help of Dr David Price (Morriston Hospital) for his assistance with database management.