The effect of dapagliflozin on renal function in patients with type 2 diabetes

Kohan, Donald E.; Fioretto, Paola; Johnsson, Kristina; Parikh, Shamik; Ptaszynska, Agata; Ying, Lei

doi:10.1007/s40620-016-0261-1

Cited by 68 publications

(59 citation statements)

References 32 publications

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“…However, this might result from a mixture of initial eGFR dipping and long-term eGFR preservation. We noticed a pattern of eGFR reduction in the short-term studies and eGFR preservation in the longer-term studies, as has been reported in several clinical trials (Cefalu et al, 2013; Kohan et al, 2014; Lambers Heerspink et al, 2013; Strojek et al, 2011; Wanner et al, 2016; Yale et al, 2013), including the EMPA-REG OUTCOME study (Wanner et al, 2016), and pooled analyses (Kohan et al, 2016; Yamout et al, 2014). This pattern, as well as the reversibility of eGFR after drug discontinuation (Barnett et al, 2014; Wanner et al, 2016), suggests that initial reduction of eGFR is probably caused by hemodynamic changes, either acute volume contraction or rapid upregulation of TGF, rather than by structural damage.…”

Section: Discussionsupporting

confidence: 79%

Effects of sodium-glucose co-transporter 2 (SGLT2) inhibition on renal function and albuminuria in patients with type 2 diabetes: a systematic review and meta-analysis

Lang

et al. 2017

PeerJ

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AimTo evaluate the effects of sodium-glucose co-transporter 2 (SGLT2) inhibition on renal function and albuminuria in patients with type 2 diabetes.MethodsWe conducted systematic searches of PubMed, Embase and Cochrane Central Register of Controlled Trials up to June 2016 and included randomized controlled trials of SGLT2 inhibitors in adult type 2 diabetic patients reporting estimated glomerular filtration rate (eGFR) and/or urine albumin/creatinine ratio (ACR) changes. Data were synthesized using the random-effects model.ResultsForty-seven studies with 22,843 participants were included. SGLT2 inhibition was not associated with a significant change in eGFR in general (weighted mean difference (WMD), −0.33 ml/min per 1.73 m2, 95% CI [−0.90 to 0.23]) or in patients with chronic kidney disease (CKD) (WMD −0.78 ml/min per 1.73 m2, 95% CI [−2.52 to 0.97]). SGLT2 inhibition was associated with eGFR reduction in short-term trials (WMD −0.98 ml/min per 1.73 m2, 95% CI [−1.42 to −0.54]), and with eGFR preservation in long-term trials (WMD 2.01 ml/min per 1.73 m2, 95% CI [0.86 to 3.16]). Urine ACR reduction after SGLT2 inhibition was not statistically significant in type 2 diabetic patients in general (WMD −7.24 mg/g, 95% CI [−15.54 to 1.06]), but was significant in patients with CKD (WMD −107.35 mg/g, 95% CI [−192.53 to −22.18]).ConclusionsSGLT2 inhibition was not associated with significant changes in eGFR in patients with type 2 diabetes, likely resulting from a mixture of an initial reduction of eGFR and long-term renal function preservation. SGLT2 inhibition was associated with statistically significant albuminuria reduction in type 2 diabetic patients with CKD.

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Section: Discussionsupporting

confidence: 79%

Effects of sodium-glucose co-transporter 2 (SGLT2) inhibition on renal function and albuminuria in patients with type 2 diabetes: a systematic review and meta-analysis

Lang

et al. 2017

PeerJ

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“…A large pooled analysis of 12 randomized clinical trials of up to 24 (4,545 patients) or 102 (3,036 patients) weeks explored the effects of dapagliflozin on renal function in patients with type 2 diabetes with normal or mildly impaired renal function (48 (48). In addition to the effects on GFR, SGLT2 inhibitors also influence albuminuria.…”

Section: Sglt2 Inhibitors and Renal Function In Clinical Studiesmentioning

confidence: 99%

SGLT2 Inhibitors and the Diabetic Kidney

et al. 2016

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Diabetic nephropathy (DN) is the most common cause of end-stage renal disease worldwide. Blood glucose and blood pressure control reduce the risk of developing this complication; however, once DN is established, it is only possible to slow progression. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, the most recent glucose-lowering oral agents, may have the potential to exert nephroprotection not only through improving glycemic control but also through glucose-independent effects, such as blood pressure-lowering and direct renal effects. It is important to consider, however, that in patients with impaired renal function, given their mode of action, SGLT2 inhibitors are less effective in lowering blood glucose. In patients with high cardiovascular risk, the SGLT2 inhibitor empagliflozin lowered the rate of cardiovascular events, especially cardiovascular death, and substantially reduced important renal outcomes. Such benefits on DN could derive from effects beyond glycemia. Glomerular hyperfiltration is a potential risk factor for DN. In addition to the activation of the renin-angiotensin-aldosterone system, renal tubular factors, including SGLT2, contribute to glomerular hyperfiltration in diabetes. SGLT2 inhibitors reduce sodium reabsorption in the proximal tubule, causing, through tubuloglomerular feedback, afferent arteriole vasoconstriction and reduction in hyperfiltration. Experimental studies showed that SGLT2 inhibitors reduced hyperfiltration and decreased inflammatory and fibrotic responses of proximal tubular cells. SGLT2 inhibitors reduced glomerular hyperfiltration in patients with type 1 diabetes, and in patients with type 2 diabetes, they caused transient acute reductions in glomerular filtration rate, followed by a progressive recovery and stabilization of renal function. Interestingly, recent studies consistently demonstrated a reduction in albuminuria. Although these data are promising, only dedicated renal outcome trials will clarify whether SGLT2 inhibitors, in addition to their glycemic and blood pressure benefits, may provide nephroprotective effects.Diabetes is a worldwide growing public health problem with high risks of severe microvascular and macrovascular complications. Diabetic nephropathy (DN) is a major burden among the chronic complications of diabetes, given that it affects ;30% of patients with diabetes. Indeed, DN is the most common cause of end-stage renal disease in the U.S. (1) and worldwide. Known risk factors for DN include hyperglycemia, hypertension, dyslipidemia, smoking, and obesity as well as ethnic, familial, and genetic predispositions (2). Key clinical trials have demonstrated that early interventions, especially those aimed at primary prevention, are by far more effective and that it is only possible to slow progression once DN is established (2). Thus, large intervention trials on the impact of long-term intensified glucose control on chronic diabetes complications, both in type 1 and type 2 diabetes (2-6), have documented the critical role of glycemic control i...

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“…[59] Dapagliflozin, on the other hand, has been studied only in patients with normal or mildly impaired renal functioning but it has been associated with favorable effects on renal end points. [6061] In a retrospective meta-analysis, dapagliflozin has also demonstrated a reduction in proteinuria, suggestive of possible benefit for the proteinuria end point. Confirmatory evidence on the renal benefit of dapagliflozin is awaited from prospective trials.…”

Section: Sodium–glucose Co-transportersmentioning

confidence: 99%

“…Confirmatory evidence on the renal benefit of dapagliflozin is awaited from prospective trials. [6061]…”

Section: Sodium–glucose Co-transportersmentioning

confidence: 99%

Safe and pragmatic use of sodium–glucose co-transporter 2 inhibitors in type 2 diabetes mellitus: South Asian Federation of Endocrine Societies consensus statement

Kalra

Ghosh

Aamir

et al. 2017

Indian J Endocr Metab

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Diabetes prevalence shows a continuous increasing trend in South Asia. Although well-established treatment modalities exist for type 2 diabetes mellitus (T2DM) management, they are limited by their side effect profile. Sodium–glucose co-transporter 2 inhibitors (SGLT2i) with their novel insulin-independent renal action provide improved glycemic control, supplemented by reduction in weight and blood pressure, and cardiovascular safety. Based on the clinical outcomes with SGLT2i in patients with T2DM, treatment strategies that make a “good clinical sense” are desirable. Considering the peculiar lifestyle, body types, dietary patterns (long duration religious fasts), and the hot climate of the South Asian population, a unanimous decision was taken to design specific, customized guidelines for T2DM treatment strategies in these regions. The panel met for a discussion three times so as to get a consensus for the guidelines, and only unanimous consensus was included. After careful consideration of the quality and strength of the available evidence, the executive summary of this consensus statement was developed based on the American Association of Clinical Endocrinologists/American College of Endocrinology protocol.

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The effect of dapagliflozin on renal function in patients with type 2 diabetes

Cited by 68 publications

References 32 publications

Effects of sodium-glucose co-transporter 2 (SGLT2) inhibition on renal function and albuminuria in patients with type 2 diabetes: a systematic review and meta-analysis

Effects of sodium-glucose co-transporter 2 (SGLT2) inhibition on renal function and albuminuria in patients with type 2 diabetes: a systematic review and meta-analysis

SGLT2 Inhibitors and the Diabetic Kidney

Safe and pragmatic use of sodium–glucose co-transporter 2 inhibitors in type 2 diabetes mellitus: South Asian Federation of Endocrine Societies consensus statement

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