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

Min, Thinzar; Wali, L; Williams, David M.; Plummer, Emily M.; Gurung, Ayeshna; Stephens, Jeffrey W.

doi:10.1080/03007995.2017.1336432

Cited by 3 publications

(1 citation statement)

References 4 publications

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“…SGLT2 inhibitors, such as dapagliflozin, have been shown to improve glomerular hyperfiltration and blood pressure [10, 11], as add-ons to their action on blood glucose and glycated hemoglobin levels. The renoprotective effect of dapagliflozin in diabetic patients is still discrepant [13, 17]. Therefore, we chose diabetic db/db mice at an age of 12 to 24 weeks to investigate the effect of dapagliflozin on renal function.…”

Section: Discussionmentioning

confidence: 99%

Dapagliflozin Aggravates Renal Injury via Promoting Gluconeogenesis in db/db Mice

Jia

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: A sodium-glucose co-transporter-2 inhibitor dapagliflozin is widely used for lowering blood glucose and its usage is limited in type 2 diabetes mellitus patients with moderate renal impairment. As its effect on kidney function is discrepant and complicated, the aim of this study is to determine the effect of dapagliflozin on the progression of diabetic nephropathy and related mechanisms. Methods: Twelve-week-old male C₅₇BL/6 wild-type and db/db mice were treated with vehicle or 1 mg/kg dapagliflozin for 12 weeks. Body weight, blood glucose, insulin tolerance, glucose tolerance, pyruvate tolerance and 24-hour urine were measured every 4 weeks. At 24 weeks of age, renal function was evaluated by blood urea nitrogen level, creatinine clearance, urine output, urinary albumin excretion, Periodic Acid-Schiff staining, Masson’s trichrome staining and electron microscopy. Changes in insulin signaling and gluconeogenic key regulatory enzymes were detected using Western blot analysis. Results: Dapagliflozin did not alleviate but instead aggravated diabetic nephropathy manifesting as increased levels of microalbuminuria, blood urea nitrogen, and glomerular and tubular damage in db/db mice. Despite adequate glycemic control by dapagliflozin, urinary glucose excretion increased after administration before 24 weeks of age and was likely associated with renal impairment. Increased urinary glucose excretion was mainly derived from the disturbance of glucose homeostasis with elevated hepatic and renal gluconeogenesis induced by dapagliflozin. Although it had no effect on insulin sensitivity and glucose tolerance, dapagliflozin further induced the expression of gluconeogenic key rate-limiting enzymes through increasing the expression levels of FoxO1 in the kidney and liver. Conclusion: These experimental results indicate that dapagliflozin aggravates diabetes mellitus-induced kidney injury, mostly through increasing gluconeogenesis.

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Section: Discussionmentioning

confidence: 99%

Dapagliflozin Aggravates Renal Injury via Promoting Gluconeogenesis in db/db Mice

Jia

Wang

et al. 2018

Cell Physiol Biochem

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Sodium-glucose co-transporter 2 inhibitors and serum uric acid

Kawada

2018

Current Medical Research and Opinion

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Renal and Cardiovascular Effects of Sodium Glucose Co-Transporter 2 Inhibitors in Patients with Type 2 Diabetes and Chronic Kidney Disease: Perspectives on the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation Trial Results

et al. 2020

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Background: Chronic kidney disease (CKD) risk is elevated in patients with type 2 diabetes mellitus (T2DM). Disease management in these patients has been generally focused on glycemic control and controlling other renal and cardiac risk factors as, historically, few protective therapies have been available. The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial of canagliflozin was the first study to demonstrate renal protection with a sodium glucose co-transporter 2 inhibitor in patients with T2DM and CKD, and these results could have important implications for clinical practice. Summary: In CREDENCE, participants with T2DM and estimated glomerular filtration rate 30–<90 mL/min/1.73 m2 and urinary albumin-creatinine ratio >300–5,000 mg/g who were treated with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for ≥4 weeks prior to randomization at either the maximum labeled or tolerated dose were randomized to receive either canagliflozin 100 mg or placebo. Canagliflozin significantly reduced the risk of the primary composite outcome of doubling of serum creatinine, end-stage kidney disease, or renal or cardiovascular (CV) death compared with placebo (hazard ratio 0.70, 95% CI 0.59–0.82; p = 0.00001). Canagliflozin also reduced the risk of secondary renal and CV outcomes. The safety profile of canagliflozin in CREDENCE was generally similar to previous studies of canagliflozin. No imbalances were observed between canagliflozin and placebo in the risk of amputation or fracture in the CREDENCE population. Key Messages: The positive renal and CV effects of canagliflozin observed in the CREDENCE trial could have a substantial impact on improving outcomes for patients with T2DM and CKD.

show abstract

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

Cited by 3 publications

References 4 publications

Dapagliflozin Aggravates Renal Injury via Promoting Gluconeogenesis in db/db Mice

Dapagliflozin Aggravates Renal Injury via Promoting Gluconeogenesis in db/db Mice

Sodium-glucose co-transporter 2 inhibitors and serum uric acid

Renal and Cardiovascular Effects of Sodium Glucose Co-Transporter 2 Inhibitors in Patients with Type 2 Diabetes and Chronic Kidney Disease: Perspectives on the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation Trial Results

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