Effect of the SGLT2 Inhibitor Dapagliflozin on Potassium Levels in Patients with Type 2 Diabetes Mellitus: A Pooled Analysis

Yavin, Yshai; Mansfield, Traci A.; Ptaszynska, Agata; Johnsson, Kristina; Parikh, Shamik; Johnsson, Eva

doi:10.1007/s13300-015-0150-y

Cited by 51 publications

(38 citation statements)

References 39 publications

(48 reference statements)

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“…In total, 27 studies yeilded data on biomarkers or on cardiovascular, renal or safety outcomes, with substantial contributions from three large cardiovascular outcome trials of empagliflozin, canagliflozin and dapagliflozin . Of the 27 studies, 18 were individual trials, eight were pooled analyses and one was a regulatory report for ertugliflozin (Figure and Supporting Information Table S2). The eight pooled analyses and one regulatory report combined data from 41 individual trials from which results were not individually available for the CKD population.…”

Section: Resultsmentioning

confidence: 99%

Effect of SGLT2 inhibitors on cardiovascular, renal and safety outcomes in patients with type 2 diabetes mellitus and chronic kidney disease: A systematic review and meta‐analysis

Toyama

Neuen

Jun

et al. 2019

Diabetes Obesity Metabolism

231

159

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Aim The use of sodium glucose co‐transporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) has been limited, primarily because glycaemic efficacy is dependent on kidney function. We performed a systematic review and meta‐analysis to assess the efficacy and safety of SGLT2 inhibitors in patients with T2DM and CKD, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Materials and methods We searched MEDLINE, EMBASE and the Cochrane Library until 7 August 2018 and websites of the US, European and Japanese regulatory authorities until 27 July 2018 for data from randomized controlled trials of SGLT2 inhibitors that included reporting of effects on biomarkers, cardiovascular, renal or safety outcomes in individuals with T2DM and CKD. Random effects models and inverse variance weighting were used to calculate relative risks with 95% confidence intervals. Results Data were obtained from 27 studies with up to 7363 participants involved. In patients with T2DM and CKD, SGLT2 inhibitors lowered glycated haemoglobin (−0.29%; 95% CI, −0.39 to −0.19) as well as blood pressure, body weight and albuminuria. SGLT2 inhibition reduced the risk of cardiovascular death, nonfatal myocardial infarction or nonfatal stroke (RR, 0.81; 95% CI, 0.70‐0.94) and heart failure (RR, 0.61; 95% CI, 0.48‐0.78), without a clear effect on all‐cause mortality (HR, 0.86; 95% CI, 0.73‐1.01). These agents also attenuated the annual decline in eGFR slope (placebo‐subtracted difference of 1.35 mL/1.73 m2/y; 95% CI, 0.78‐1.93) and reduced the risk of the composite renal outcome (HR, 0.71; 95% CI, 0.53‐0.95). There was no evidence of additional risks with SGLT2 inhibition in CKD beyond those already known for the class, although heterogeneity was observed across individual agents for some safety outcomes. Conclusion Currently available data suggest that, despite only modest reductions in glycated haemoglobin, SGLT2 inhibitors reduce the risk of cardiovascular and renal outcomes in patients with T2DM and CKD, without clear evidence of additional safety concerns.

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Section: Resultsmentioning

confidence: 99%

Effect of SGLT2 inhibitors on cardiovascular, renal and safety outcomes in patients with type 2 diabetes mellitus and chronic kidney disease: A systematic review and meta‐analysis

Toyama

Neuen

Jun

et al. 2019

Diabetes Obesity Metabolism

231

159

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“…However, despite the fact that they might trigger volume depletion and stimulate the tubule‐glomerular feedback, available evidence suggests that SGLT2is are associated with mild changes in serum electrolyte levels. Indeed, no effect on plasma sodium levels and only small increases in serum potassium, calcium, phosphate, and magnesium concentrations have been found in clinical trials …”

Section: Clinical and Preclinical Studies On Electrolytes Imbalancesmentioning

confidence: 99%

Mineral and Electrolyte Disorders With SGLT2i Therapy

et al. 2019

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The newly developed sodium‐glucose cotransporter 2 inhibitors (SGLT2is) effectively modulate glucose metabolism in diabetes. Although clinical data suggest that SGLT2is (empagliflozin, dapagliflozin, ertugliflozin, canagliflozin, ipragliflozin) are safe and protect against renal and cardiovascular events, very little attention has been dedicated to the effects of these compounds on different electrolytes. As with other antidiabetic compounds, some effects on water and electrolytes balance have been documented. Although the natriuretic effect and osmotic diuresis are expected with SGLT2is, these compounds may also modulate urinary potassium, magnesium, phosphate, and calcium excretion. Notably, they have had no effect on plasma sodium levels and promoted only small increases in serum potassium and magnesium concentrations in clinical trials. Moreover, SGLT2is may induce an increase in serum phosphate, FGF‐23, and PTH; reduce 1,25‐dihydroxyvitamin D; and generate normal serum calcium. Some published and preliminary reports, as well as unconfirmed reports have suggested an association with bone fractures. Some homeostasis perturbations are transient, whereas others may persist, suggesting that the administration of SGLT2is may affect electrolyte balances in exposed subjects. Although current evidence supports their safety, additional efforts are needed to elucidate the long‐term impact of these compounds on chronic kidney disease, mineral metabolism, and bone health. Indeed, the limited follow‐up studies and the heterogeneity of the case‐mix of different randomized controlled trials preclude a definitive answer on the impact of these compounds on long‐term outcomes such as the risk of bone fracture. Here we review the current understanding of the mechanisms involved in electrolyte handling and the available data on the clinical implications of electrolytes and mineral metabolism perturbations induced by SGLT2i administration. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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“…Its BP-lowering properties were particularly favorable in patients already receiving a β blocker or calcium-channel blocker [34]. Also, even when used in patients receiving angiotensin receptor blockers/angiotensin converting enzyme inhibitors or potassium-sparing diuretics or in those with moderate renal impairment, no increased risk for hyperkalemia has been detected [35]. Of interest, the reduction in BP is not associated with significant changes in heart rate.…”

Section: Blood Pressurementioning

confidence: 99%

A consensus statement for the clinical use of the renal sodium-glucose co-transporter-2 inhibitor dapagliflozin in patients with type 2 diabetes mellitus

Avogaro

Giaccari

Fioretto

et al. 2017

Expert Review of Clinical Pharmacology

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Introduction: The present review developed a clinical consensus based on a Delphi method on Dapagliflozin, a selective inhibitor of the renal sodium-glucose co-transporter-2 (SGLT2-I) in the treatment of patients with Type 2 diabetes mellitus. Areas covered: Panel members, using a 5-point scale, were asked to rate 9 statements on pharmakodinamic, mode of action on glycaemic and extra-glycaemic effects, and safety of dapaglifozin, Members also aimed to identify the patient most susceptible to the treatment with dapagliflozin . Expert commentary: Dapagliflozin is effective in lowering the plasma glucose concentration with a good safety profile. Dapagliflozin can be utilized in combination with all other antihyperglycaemic agents at all stages of the disease: however, a reduced GFR limits its efficacy. As for the other drugs of the class, Dapagliflozin positively modifies other risk factors for CV disease: these effects will be tested in the so far largest cardiovascular outcome trial for the SGLT2 inhibitors so far, the DECLARE trial, which will communicate whether this class of drugs will be disease-modifier in patients with type 2 diabetes also in primary prevention.

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Effect of the SGLT2 Inhibitor Dapagliflozin on Potassium Levels in Patients with Type 2 Diabetes Mellitus: A Pooled Analysis

Cited by 51 publications

References 39 publications

Effect of SGLT2 inhibitors on cardiovascular, renal and safety outcomes in patients with type 2 diabetes mellitus and chronic kidney disease: A systematic review and meta‐analysis

Effect of SGLT2 inhibitors on cardiovascular, renal and safety outcomes in patients with type 2 diabetes mellitus and chronic kidney disease: A systematic review and meta‐analysis

Mineral and Electrolyte Disorders With SGLT2i Therapy

A consensus statement for the clinical use of the renal sodium-glucose co-transporter-2 inhibitor dapagliflozin in patients with type 2 diabetes mellitus

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