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, André

doi:10.1016/j.diabres.2016.09.016

Cited by 43 publications

(29 citation statements)

References 78 publications

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“…One marked difference between LEADER and EMPA-REG OUTCOME is the distinctive outcome of a 35% (P < 0.001) reduction in hospitalizations for HF reported with empagliflozin, whereas only a slight, non-significant reduction was noted with liraglutide (-13%, P = 0.14; Table 4). Both liraglutide and empagliflozin reduce systolic blood pressure, an independent risk factor of HF, but the insignificant difference vs the placebo arm in T2D patients with blood pressure already well controlled at baseline cannot explain the marked reduction in hospitalizations for HF in the EMPA-REG OUTCOME [52].…”

Section: Lessons From Leadermentioning

confidence: 97%

GLP-1 receptor agonists and heart failure in diabetes

Scheen

2017

Diabetes & Metabolism

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The prevalence of heart failure (HF) is increasing in patients with type 2 diabetes (T2D), and glucose-lowering agents have distinctive effects on the risk of developing HF that requires hospitalization. Such an increased risk has been consistently reported with thiazolidinediones (glitazones) and perhaps also with the dipeptidyl peptidase (DPP)-4 inhibitor saxagliptin (at least in SAVOR -TIMI 53), whereas a markedly decreased risk was highlighted with the sodium -glucose cotransporter type 2 (SGLT2) inhibitor empagliflozin in EMPA-REG OUTCOME. Yet, the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on myocardial function remain controversial. Whereas some promising observations have been reported in various animal models, the effects of GLP-1RAs on myocardial function in humans are more heterogeneous, while the positive effect on left ventricular ejection fraction (LVEF), if any, appears to be inconsistent and rather modest in most patients with HF. However, no increased risk of hospitalization for HF has been reported with GLP-1RAs in meta-analyses of phase-II/III trials (exenatide, albiglutide, dulaglutide, liraglutide), demonstrating the safety of this pharmacological class, and such findings have been confirmed by three large prospective cardiovascular outcome trials (ELIXA with lixisenatide, LEADER with liraglutide and SUSTAIN-6 with semaglutide). In particular, LEADER reported a trend towards a reduction in HF hospitalization (-13%, P = 0.14), together with a significant reduction in cardiovascular and all-cause mortality in patients with T2D at risk of cardiovascular disease. These results are reassuring in the face of the somewhat negative results of the FIGHT trial, which evaluated the effects of liraglutide in patients with advanced HF and low LVEF, such that further studies and caution are now required when using this agent to treat such patients in clinical practice.

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Section: Lessons From Leadermentioning

confidence: 97%

GLP-1 receptor agonists and heart failure in diabetes

Scheen

2017

Diabetes & Metabolism

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“…[68,69]. It is unlikely, however, that they could be explained either by the modest reduction in glycated haemoglobin (HbA1c, though equipoise glucose control in both arms was not achieved), or by the slight reduction in arterial blood pressure in already wellcontrolled T2D patients, [70] or by a common diuretic effect. [71] Even a combination of all these mechanisms appears insufficient to explain the drastic reduction in mortality so that other hemodynamic [67] or metabolic [72] mechanistic alternatives have been proposed, which are not mutually exclusive but still remain to be confirmed.…”

Section: Empa-reg Outcome Trialmentioning

confidence: 98%

Pharmacological management of type 2 diabetes: what’s new in 2017?

Scheen

2017

Expert Review of Clinical Pharmacology

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IntroductionNovelties in the management of type 2 diabetes are dominated by the commercialisation of new glucose-lowering agents, which offer alternatives to older antidiabetic medications, and by the publication of several prospective placebo-controlled outcome trials, which demonstrated not only cardiovascular safety but also cardiovascular and renal protection with some new medications. Areas coveredUpdates regarding the use of glucose-lowering agents are discussed from a clinical point of view. Some new viewpoints concern older antidiabetic agents such as metformin, sulfonylureas and glitazones whose benefit-risk balance has been revisited, especially in high risk patients. The recent data regarding DPP-4 inhibitors (gliptins) focused on the safety profile of this pharmacological class, including in patients with impaired renal function. The highlight concerns the cardiovascular (and renal) protection by some GLP-1 receptor agonists (liraglutide, semaglutide) and SGLT2 inhibitors (empagliflozin, canagliflozin) in patients with high cardiovascular risk. Finally, efficacy and safety of new combinations and advances in insulin therapy will be briefly discussed. Expert Opinion/commentaryThe recent data from randomized controlled trials, meta-analyses and observational real-life studies should trigger a revision of the algorithm for the treatment of hyperglycemia in type 2 diabetes, especially in patients with high cardiovascular and/or renal risk.

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“…SGLT-2 inhibitors improve glycemic control, reduce body weight and blood pressure, and are associated with a low risk of hypoglycemia [68]. In clinical trials, an SGLT2 inhibitor (empagliflozin) was found to have a profound effect in reducing cardiovascular and all-cause mortality in patients with T2DM and antecedents of cardiovascular disease [67]. This effect, however, was attributed mostly to a hemodynamic rather than a metabolic effect in part due to osmotic/diuretic effect of the SGLT2 and to the reduction in arterial blood pressure.…”

Section: Kidneysmentioning

confidence: 99%

“…In T2DM subjects, all of the filtered glucose in excess of the Tm is excreted in the urine [64][65][66]. Because sodium and glucose are cotransported in renal proximal tubular cells, T2DM subjects have an increase in total body sodium content and a high risk of hypertension [67]. Inhibition of SGLT-2, which is responsible for approximately 90% of renal glucose reabsorption, increases urinary glucose excretion and lowers blood glucose concentrations.…”

Section: Kidneysmentioning

confidence: 99%

Can Avicenna Help Manage the Diabetes Epidemic in Central Asia?

Sharofova,

Nuraliev,

Sukhrobov

et al. 2017

Cent. Asian j. Med. Sci.

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Objectives:The fast-rising rate of diabetes incidents is a growing concern in Central Asian countries. This article reviews the current understanding of type 2 diabetes etiology, progression and treatment options along with opportunities for utilizing Avicenna's legacy in developing novel botanical therapeutics. Methods: Analysis of relevant publications, including a variety of Avicenna's work in Arabic, English and Russian. Results: With conventional treatment strategy shifting from single-component drugs aimed at one target to multitherapeutic combinations addressing the complex nature of many diseases and conditions, the role of multicomponent botanical preparations may increase. Diabetes mellitus is a serious chronic, progressive disease characterized by hyperglycemia, which is associated with a variety of comorbidities because of considerable damage, dysfunction and failure of multiple organs developed through the disease's progression. Multidisciplinary collaborative research that encompasses innovative tools could be used for effective development of new comprehensive therapeutic products and treatments based on knowledge of traditional medicine and supported by contemporary scientific validation. Conclusion: Comprehensive analysis of Avicenna's 1,000-year-old approach to the treatment of prediabetes and diabetes provides valuable directions in the search for plant-based treatments. Botanical therapeutics may provide relatively inexpensive and safe methods for diabetes treatment.

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

Cited by 43 publications

References 78 publications

GLP-1 receptor agonists and heart failure in diabetes

GLP-1 receptor agonists and heart failure in diabetes

Pharmacological management of type 2 diabetes: what’s new in 2017?

Can Avicenna Help Manage the Diabetes Epidemic in Central Asia?

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