Effects of glucose-lowering agents on vascular outcomes in type 2 diabetes: A critical reappraisal

Scheen, André; Charbonnel, B.

doi:10.1016/j.diabet.2014.03.004

Cited by 65 publications

(23 citation statements)

References 82 publications

(100 reference statements)

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“…These impressive results strongly contrast with several disappointing results previously reported with other glucose-lowering agents in T2D [6], and are also more favourable than those reported with metformin in high-risk populations [7]. A recent systematic review and meta-analysis suggested that results for other SGLT2 inhibitors (specifically, canagliflozin and dapagliflozin) may not be clearly different, although results from ongoing studies will be crucial for substantiating these findings across the drug class [8].…”

Section: Introductioncontrasting

confidence: 67%

Reappraisal of the diuretic effect of empagliflozin in the EMPA-REG OUTCOME trial: Comparison with classic diuretics

Scheen

2016

Diabetes & Metabolism

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Section: Introductioncontrasting

confidence: 67%

Reappraisal of the diuretic effect of empagliflozin in the EMPA-REG OUTCOME trial: Comparison with classic diuretics

Scheen

2016

Diabetes & Metabolism

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“…Past history of cardiovascular disease or congestive heart failure may represent a key criterion of choice considering the remarkable efficacy of the SGLT2i empagliflozin in EMPA-REG OUTCOME [11,12], contrasting with previous mitigated results reported with other glucose-lowering agents, including DPP-4i [61]. Thus, in clinical practice, the choice should be individualized according to individual characteristics of the patient [62].…”

Section: Expert Opinionmentioning

confidence: 82%

DPP-4 inhibitor plus SGLT-2 inhibitor as combination therapy for type 2 diabetes: from rationale to clinical aspects

Scheen

2016

Expert Opinion on Drug Metabolism & Toxicology

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SUMMARYIntroduction : Type 2 diabetes (T2D) is a complex disease with multiple defects, which generally require a combination of several pharmacological approaches to control hyperglycemia. Combining a dipeptidyl peptidase-4 inhibitor (DPP-4i) and a sodium-glucose cotransporter type 2 inhibitor (SGT2i) appears to be an attractive approach.Area covered: An extensive literature search was performed to analyze the pharmacokinetics, pharmacodynamics and clinical experience of different gliptin-gliflozin combinations.Expert opinion: There is a strong rationale for combining a DPP-4i and a SGLT2i in patients with T2D because the two drugs exert different and complementary glucose-lowering effects.Dual therapy (initial combination or stepwise approach) is more potent than either monotherapy in patients treated with diet and exercise or already treated with metformin.Combining the two pharmacological options is safe and does not induce hypoglycemia. The additional glucose-lowering effect is more marked when a gliflozin is added to a gliptin than when a gliptin is added to a gliflozin. Two fixed-dose combinations (FDCs) are already available (saxagliptin-dapagliflozin and linagliptin-empagliflozin) and others are in current development. Bioequivalence of the two compounds given as FDC tablets was demonstrated when compared with coadministration of the individual tablets. FDCs could simplify the antihyperglycaemic therapy and improve drug compliance. Article highlights box -Type 2 diabetes (T2D) often requires the combination of several medications with complementary actions to reach glucose control targets while limiting side effects -The combination of a dipeptidyl peptidase-4 inhibitor (DPP-4i) and a sodium-glucose cotransporter type 2 inhibitor (SGLT2i) is an attractive approach for the management of T2D. Keywords-Both saxagliptin plus dapagliflozin and linagliptin plus empagliflozin combined therapies have been tested as separate tablets (no clinically relevant pharmacokinetic drug-drug interactions) and as fixed-dose combination (FDC : bioequivalence studies).-DPP-4i -SGLT2i combined therapies are more efficacious than either monotherapy to control blood glucose, without worsening of the safety profile.-Initial DPP-4i -SGLT2i combination may be considered or one compound may the added to the other. However, which one should be used in first place remains an open question.

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“…After the UKPDS [5], most CV outcome trials with glucose-lowering agents gave rather disappointing results [15][16][17][18]. Dipeptidyl peptidase-4 inhibitors (gliptins), which exert almost a neutral effect on BP [19], proved non-inferiority but no superiority versus placebo, demonstrating the CV safety of this pharmacological class but not its efficacy in preventing CV events [20].…”

Section: Introductionmentioning

confidence: 99%

Effects of reducing blood pressure on cardiovascular outcomes and mortality in patients with type 2 diabetes: Focus on SGLT2 inhibitors and EMPA-REG OUTCOME

Scheen

2016

Diabetes Research and Clinical Practice

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Please cite this article as: A.J. Scheen, Effects of reducing blood pressure on cardiovascular outcomes and mortality in patients with type 2 diabetes: focus on SGLT2 inhibitors and EMPA-REG OUTCOME, Diabetes Research and Clinical Practice (2016), doi: http://dx.doi.org/10.1016/j.diabres. 2016.09.016 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. SummaryEmpagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has shown a remarkable reduction in cardiovascular and all-cause mortality in patients with type 2 diabetes (T2D) and antecedents of cardiovascular disease in the EMPA-REG OUTCOME trial. This effect has been attributed to a hemodynamic rather than a metabolic effect, partly due to the osmotic/diuretic effect of empagliflozin and to the reduction in arterial blood pressure. The present review will : 1) summarize the results of specific studies having tested the blood pressure lowering effects of SGLT2 inhibitors; 2) describe the results of meta-analyses of trials having evaluated the effects on mortality and cardiovascular outcomes of lowering blood pressure in patients with T2D, with a special focus on baseline and target blood pressures; 3) compare the cardiovascular outcome results in EMPA-REG OUTCOME versus other major trials with antihypertensive agents in patients with T2D; and 4) evaluate post-hoc analyses from EMPA-REG OUTCOME, especially subgroups of patients of special interest regarding the blood pressure lowering hypothesis. Although BP reduction associated to empagliflozin therapy may partly contribute to the benefits reported in EMPA-REG OUTCOME, other mechanisms most probably play a greater role in the overall CV protection and reduction in mortality observed in this trial.

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Effects of glucose-lowering agents on vascular outcomes in type 2 diabetes: A critical reappraisal

Cited by 65 publications

References 82 publications

Reappraisal of the diuretic effect of empagliflozin in the EMPA-REG OUTCOME trial: Comparison with classic diuretics

Reappraisal of the diuretic effect of empagliflozin in the EMPA-REG OUTCOME trial: Comparison with classic diuretics

DPP-4 inhibitor plus SGLT-2 inhibitor as combination therapy for type 2 diabetes: from rationale to clinical aspects

Effects of reducing blood pressure on cardiovascular outcomes and mortality in patients with type 2 diabetes: Focus on SGLT2 inhibitors and EMPA-REG OUTCOME

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