Improved Insulin Sensitivity With Angiotensin Receptor Neprilysin Inhibition in Individuals With Obesity and Hypertension

Jordan, Jens; Stinkens, Rudi; Jax, Thomas; Engeli, Stefan; Blaak, Ellen E.; May, Marcus; Havekes, Bas; Schindler, Christoph; Albrecht, Diego; Pal, Parasar; Heise, Tim; Goossens, Gijs H.; Langenickel, Thomas

doi:10.1002/cpt.455

Cited by 94 publications

(80 citation statements)

References 39 publications

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“…Abdominal adipose tissue interstitial glycerol concentrations increased with sacubitril/valsartan, but decreased with amlodipine. It seems that sacubitril/valsartan treatment leads to a metabolic benefit in the study population and supports the relevance of neprilysin inhibition along with AT1-receptor blockade in the regulation of human glucose and lipid metabolism [35,36]. However, the underlying pathophysiologic mechanisms are not yet clear and may be attributed to changes in the production and concentrations of various metabolically active peptides by neprilysin inhibition (i.e.…”

Section: Diabetes Mellitus Cardiovascular and Chronic Kidney Diseasessupporting

confidence: 59%

Τhe role of sacubitril/valsartan therapy on renal function and glucose metabolism in chronic heart failure patients

Chrysοhoou¹,

Tousoulis²

2017

Integr Obesity Diabetes

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Section: Diabetes Mellitus Cardiovascular and Chronic Kidney Diseasessupporting

confidence: 59%

Τhe role of sacubitril/valsartan therapy on renal function and glucose metabolism in chronic heart failure patients

Chrysοhoou¹,

Tousoulis²

2017

Integr Obesity Diabetes

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“…33 In a study comparing the effects of sacubitril/valsartan and amlodipine on insulin resistance in 92 obese hypertensive patients treated for 8 weeks, those treated with sacubitril/valsartan showed a significant increase in insulin sensitivity using the hyperinsulinaemic-euglycaemic clamp technique. 9 …”

Section: Discussionmentioning

confidence: 99%

“…Sacubitril/valsartan improved peripheral insulin sensitivity in obese hypertensive patients, 9 whereas omapatrilat, a dual angiotensin-converting-enzyme–neprilysin inhibitor, has potent insulin-sensitising effects experimentally, increasing myocardial glucose uptake in Zucker fatty rats, 10 although there are no data on the effect of omapatrilat on insulin sensitivity and glycaemic control in humans. We therefore investigated the effect of sacubitril/valsartan versus enalapril on HbA 1c in patients with diabetes and HFrEF enrolled in PARADIGM-HF, as well as the influence of these regimens on the initiation of oral antihyperglycaemic and insulin therapy in patients with diabetes.…”

Section: Introductionmentioning

confidence: 99%

Effect of sacubitril/valsartan versus enalapril on glycaemic control in patients with heart failure and diabetes: a post-hoc analysis from the PARADIGM-HF trial

Seferović

Claggett

Seidelmann

et al. 2017

The Lancet Diabetes & Endocrinology

280

211

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Summary Background Diabetes is an independent risk factor for heart failure progression. Sacubitril/valsartan, a combination angiotensin receptor-neprilysin inhibitor, improves morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF), compared with the angiotensin-converting enzyme inhibitor enalapril, and improves peripheral insulin sensitivity in obese hypertensive patients. We aimed to investigate the effect of sacubitril/valsartan versus enalapril on HbA1c and time to first-time initiation of insulin or oral antihyperglycaemic drugs in patients with diabetes and HFrEF. Methods In a post-hoc analysis of the PARADIGM-HF trial, we included 3778 patients with known diabetes or an HbA1c≥6·5% at screening out of 8399 patients with HFrEF who were randomly assigned to treatment with sacubitril/valsartan or enalapril. Of these patients, most (98%) had type 2 diabetes. We assessed changes in HbA1c, triglycerides, HDL cholesterol and BMI in a mixed effects longitudinal analysis model. Times to initiation of oral antihyperglycaemic drugs or insulin in subjects previously not treated with these agents were compared between treatment groups. Findings There were no significant differences in HbA1c concentrations between randomised groups at screening. During the first year of follow-up, HbA1c concentrations decreased by 0·16% (SD 1·40) in the enalapril group and 0·26% (SD 1·25) in the sacubitril/valsartan group (between-group reduction 0·13%, 95% CI 0·05–0·22, p=0·0023). HbA1c concentrations were persistently lower in the sacubitril/valsartan group than in the enalapril group over the 3-year follow-up (between-group reduction 0·14%, 95% CI 0·06–0·23, p=0·0055). New use of insulin was 29% lower in patients receiving sacubitril/valsartan (114 [7%] patients) compared with patients receiving enalapril (153 [10%]; hazard ratio 0·71, 95% CI 0·56–0·90, p=0·0052). Similarly, fewer patients were started on oral antihyperglycaemic therapy (0·77, 0·58–1·02, p=0·073) in the sacubitril/valsartan group. Interpretation Patients with diabetes and HFrEF enrolled in PARADIGM-HF who received sacubitril/valsartan had a greater long-term reduction in HbA1c than those receiving enalapril. These data suggest that sacubitril/valsartan might enhance glycaemic control in patients with diabetes and HFrEF.

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“…82 Drugs that are efficacious, therefore, in diabetic HFrEF are β-blockers, ACE inhibitors and the sacubitril/valsartan combination. 82 Drugs that are efficacious, therefore, in diabetic HFrEF are β-blockers, ACE inhibitors and the sacubitril/valsartan combination.…”

Section: Diagnosis Screening and Therapymentioning

confidence: 99%

Heart failure in the patient with diabetes: Epidemiology, aetiology, prognosis, therapy and the effect of glucose‐lowering medications

Bell¹,

Goncalves

2019

Diabetes Obesity Metabolism

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In people with type 2 diabetes the frequency of heart failure (HF) is increased and mortality from HF is higher than with non-diabetic HF. The increased frequency of HF is attributable to the cardiotoxic tetrad of ischaemic heart disease, left ventricular hypertrophy, diabetic cardiomyopathy and an extracellular volume expansion resistant to atrial natriuretic peptides. Activation of the renin-angiotensin-aldosterone system and sympathetic nervous systems results in cardiac remodelling, which worsens cardiac function. Reversal of remodelling can be achieved, and cardiac function improved in people with HF with reduced ejection fraction (HFrEF) by treatment with angiotensin-converting enzyme inhibitors and β-blockers. However, with HF with preserved ejection fraction (HFpEF), only therapy for the underlying risk factors helps.Blockers of mineralocorticoid receptors may be beneficial in both HFrEF and HFpEF. Glucoselowering drugs can have a negative effect (insulin, sulphonylureas, dipeptidyl peptidase-4 inhibitors and thiazolidinediones), a neutral effect (α-glucosidase inhibitors and glucagon-like peptide-1 receptor agonists) or a positive effect (sodium-glucose co-transporter-2 inhibitors and metformin).antidiabetic drug, GLP-1 analogue, heart failure, insulin therapy, SGLT2 inhibitor, thiazolidinediones 1 | INTRODUCTION Heart failure (HF) results from structural and/or functional impairment of ventricular filling and/or ejection 1 and it is a common and serious comorbidity of type 2 diabetes. 2 In the present review we document the increased incidence of HF, and the reasons for this increase, as well as its poor prognosis in patients with diabetes.The potential therapies to both prevent and treat HF are discussed, in addition to the positive and negative effects of glucoselowering medications.Several reviews on this important subject have been recently published 3-7 ; however, this is a rapidly evolving field. An important limitation has been that HF was not a primary endpoint in most cardiovascular (CV) outcome trials, and it has been the most heterogeneously distributed outcome. | EPIDEMIOLOGYAs long ago as the Framingham Heart Study, HF was shown to be twice as common in men with diabetes and five times more common in women with diabetes between the ages of 45 and 74 years when compared with age-matched non-diabetic controls, and, in those aged ≤65 years, there was a fourfold increase in the prevalence of HF in men with diabetes and an eightfold increase in women with diabetes. 8In almost 10 000 patients with type 2 diabetes enrolled in a Health Maintenance Organization, 12% had HF at entry. Independent risk factors for the presence of HF were older age, longer duration of diabetes, use of insulin and lower body mass index (BMI). 9 In addition, those with type 2 diabetes who did not have HF at entry developed HF at a rate of 3.3% per year. The Reykjavik Study reported a 12% prevalence of HF in people with diabetes compared with 3% in people

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Improved Insulin Sensitivity With Angiotensin Receptor Neprilysin Inhibition in Individuals With Obesity and Hypertension

Cited by 94 publications

References 39 publications

Τhe role of sacubitril/valsartan therapy on renal function and glucose metabolism in chronic heart failure patients

Τhe role of sacubitril/valsartan therapy on renal function and glucose metabolism in chronic heart failure patients

Effect of sacubitril/valsartan versus enalapril on glycaemic control in patients with heart failure and diabetes: a post-hoc analysis from the PARADIGM-HF trial

Heart failure in the patient with diabetes: Epidemiology, aetiology, prognosis, therapy and the effect of glucose‐lowering medications

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