Effects of sodium-glucose co-transporter 2 inhibitors on blood pressure: A systematic review and meta-analysis

Baker, William L.; Smyth, Lindsay R.; Riche, Daniel M.; Bourret, Emily M.; Chamberlin, Kevin W.; White, William Β.

doi:10.1016/j.jash.2014.01.007

Cited by 385 publications

(289 citation statements)

References 53 publications

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“…It has been reported that treatment either as monotherapy or add‐on therapy with another SGLT2 inhibitor such as canagliflozin, empagliflozin, ipragliflozin, luseogliflozin, and tofogliflozin is associated with a small but significant reduction in SBP and DBP 67. Our findings of the effects of SGLT2 inhibitors on BP are similar to a recent systematic review by Baker et al69 and a recent meta‐analysis of efficacy and safety of SGLT2 inhibitors 70…”

Section: Discussionsupporting

confidence: 88%

“…The BP reductions observed with the SGLT2 inhibitors may result from their chronic natriuretic and osmotic diuretic effects. It has been reported that SGLT2 inhibitors increase urinary output by between 107 and 470 mL/d 69. Therefore, the increased urinary sodium excretion may reduce plasma volume, resulting in reduced BP, particularly with increasing age 20.…”

Section: Discussionmentioning

confidence: 99%

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Effect of Sodium‐Glucose Cotransport‐2 Inhibitors on Blood Pressure in People With Type 2 Diabetes Mellitus: A Systematic Review and Meta‐Analysis of 43 Randomized Control Trials With 22 528 Patients

Mazidi

Rezaie

Gao

et al. 2017

JAHA

256

174

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BackgroundThe sodium‐glucose cotransporter 2 (SGLT2) inhibitors are a class of oral hypoglycemic agents. We undertake a systematic review and meta‐analysis of prospective studies to determine the effect of SGLT2 on blood pressure (BP) among individuals with type 2 diabetes mellitus.Methods and ResultsPubMed‐Medline, Web of Science, Cochrane Database, and Google Scholar databases were searched to identify trial registries evaluating the impact of SGLT2 on BP. Random‐effects models meta‐analysis was used for quantitative data synthesis. The meta‐analysis indicated a significant reduction in systolic BP following treatment with SGLT2 (weighted mean difference −2.46 mm Hg [95% CI −2.86 to −2.06]). The weighted mean differences for the effect on diastolic BP was −1.46 mm Hg (95% CI −1.82 to −1.09). In these subjects the weighted mean difference effects on serum triglycerides and total cholesterol were −2.08 mg/dL (95% CI −2.51 to −1.64) and 0.77 mg/dL (95% CI 0.33‐1.21), respectively. The weighted mean differences for the effect of SGLT2 on body weight was −1.88 kg (95% CI −2.11 to −1.66) across all studies. These findings were robust in sensitivity analyses.ConclusionsTreatment with SGLT2 glucose cotransporter inhibitors therefore has beneficial off‐target effects on BP in patients with type 2 diabetes mellitus and may also be of value in improving other cardiometabolic parameters including lipid profile and body weight in addition to their expected effects on glycemic control. However, our findings should be interpreted with consideration for the moderate statistical heterogeneity across the included studies.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Effect of Sodium‐Glucose Cotransport‐2 Inhibitors on Blood Pressure in People With Type 2 Diabetes Mellitus: A Systematic Review and Meta‐Analysis of 43 Randomized Control Trials With 22 528 Patients

Mazidi

Rezaie

Gao

et al. 2017

JAHA

256

174

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“…The within‐group analysis in the total cohort showed improvements in HbA1c (−0.7%), FPG (−28.2 mg/dL), body weight (−2.7 kg) and systolic blood pressure (−3.0 mm Hg) after initiation of dapagliflozin that were consistent with findings from phase III RCTs 2, 3. A benefit for lipid profile was also observed, confirming the increase in HDL cholesterol and reduction of triglycerides seen in RCTs,15 but with no significant increase in LDL cholesterol.…”

Section: Discussionsupporting

confidence: 75%

Use and effectiveness of dapagliflozin in routine clinical practice: An Italian multicentre retrospective study

Fadini

Zatti

Baldi

et al. 2018

Diabetes Obesity Metabolism

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In randomized controlled trials (RCTs), sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors have been shown to confer glycaemic and extra‐glycaemic benefits. The DARWIN‐T2D (DApagliflozin Real World evIdeNce in Type 2 Diabetes) study was a multicentre retrospective study designed to evaluate the baseline characteristics of patients receiving dapagliflozin vs those receiving selected comparators (dipeptidyl peptidase‐4 inhibitors, gliclazide, or glucagon‐like peptide‐1 receptor agonists), and drug effectiveness in routine clinical practice. From a population of 281 217, the analysis included 17 285 patients initiating dapagliflozin or comparator glucose‐lowering medications (GLMs), 6751 of whom had a follow‐up examination. At baseline, participants starting dapagliflozin were younger, had a longer disease duration, higher glycated haemoglobin (HbA1c) concentration, and a more complex history of previous GLM use, but the clinical profile of patients receiving dapagliflozin changed during the study period. Dapagliflozin reduced HbA1c by 0.7%, body weight by 2.7 kg, and systolic blood pressure by 3.0 mm Hg. Effects of comparator GLMs were also within the expected range, based on RCTs. This real‐world study shows an initial channelling of dapagliflozin to difficult‐to‐treat patients. Nonetheless, dapagliflozin provided significant benefits with regard to glucose control, body weight and blood pressure that were in line with findings from RCTs.

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“…Weight reduction and sodium depletion also contribute to this finding. 23,24 In addition, a direct vascular effect, with reduced arterial stiffness, leads to BP change. 25 The effect of this class on serum lipid levels is mild.…”

Section: The Kidney As a Treatment Targetmentioning

confidence: 99%

“…Greater attention should be given to the elderly, who are more sensitive to the risk of hypotension, especially those who use diuretics. 23,24 A more serious and potentially fatal but uncommon adverse effect is the risk of diabetic ketoacidosis (DKA), rare in T2DM but more common in T1DM. These drugs are being used in addition to what has been approved by Anvisa, as an adjunct to insulin treatment in T1DM.…”

Section: The Kidney As a Treatment Targetmentioning

confidence: 99%

Use of SGLT-2 inhibitors in the treatment of type 2 diabetes mellitus

Santos¹,

Lima

Sousa‐Rodrigues³

et al. 2017

Rev. Assoc. Med. Bras.

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Summary Introduction: Diabetes mellitus is one of the most common chronic diseases in the world, with high morbidity and mortality rates, resulting in a greatly negative socioeconomic impact. Although there are several classes of oral antidiabetic agents, most of the patients are outside the therapeutic goal range. Objective: To review the use of SGLT-2 inhibitors in the treatment of type 2 diabetes mellitus, focusing on their favorable and unfavorable effects, as well as on cardiovascular profile. Method: A literature search on Pubmed database was performed using the following keywords: "SGLT-2 inhibitors," "dapagliflozin," "empagliflozin," "canagliflozin." Results: SGLT-2 inhibitors are a class of oral antidiabetic drugs directed to the kidney. Their mechanism of action is to reduce blood glucose by inducing glycosuria. Extra-glycemic benefits have been described, such as weight loss, decline in blood pressure and levels of triglycerides and uric acid, and they can slow the progression of kidney disease. Genitourinary infections are the main side effects. There is a low risk of hypotension and hypoglycemia. Diabetic ketoacidosis is a serious adverse effect, although rare. Empagliflozin has already had its cardiovascular benefit demonstrated and studies with other drugs are currently being performed. Conclusion: SGLT-2 inhibitors are a new treatment option for type 2 diabetes mellitus, acting independently of insulin. They have potential benefits other than the reduction of blood glucose, but also carry a risk for adverse effects.

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Effects of sodium-glucose co-transporter 2 inhibitors on blood pressure: A systematic review and meta-analysis

Cited by 385 publications

References 53 publications

Effect of Sodium‐Glucose Cotransport‐2 Inhibitors on Blood Pressure in People With Type 2 Diabetes Mellitus: A Systematic Review and Meta‐Analysis of 43 Randomized Control Trials With 22 528 Patients

Effect of Sodium‐Glucose Cotransport‐2 Inhibitors on Blood Pressure in People With Type 2 Diabetes Mellitus: A Systematic Review and Meta‐Analysis of 43 Randomized Control Trials With 22 528 Patients

Use and effectiveness of dapagliflozin in routine clinical practice: An Italian multicentre retrospective study

Use of SGLT-2 inhibitors in the treatment of type 2 diabetes mellitus

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