sacubitril and Diabetes-Mellitus

Sacubitril/valsartan and angiotensin-converting enzyme inhibitor (ACEI)/angiotensin-receptor blocker (ARB) therapies were reported to affect glycaemic control and the development of diabetes mellitus (DM), but the findings are inconsistent. We examined the evidence for the effects of sacubitril/valsartan and ACEI/ARB in DM by conducting a meta-analysis.. The Cochrane Central Register of Controlled Trials (The Cochrane Library), Embase, PubMed, and ClinicalTrials.gov were searched for data from randomised clinical trials (RCTs) that evaluated the efficacy of sacubitril/valsartan and ACEI/ARB in patients, as of May 25, 2022. Patients were grouped by their disease background at baseline. The main outcomes were the number of new-onset DM and hypoglycaemia, elevated glycaemia, inadequate DM control, diabetes treatment, and diabetic complications, from baseline to the end of the trials. The risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials (ROB 2). The quality of the evidence was evaluated according to the Recommendations for Assessment, Development, and Evaluation guidelines. The meta-analysis of the incidence of various outcomes was conducted using fixed or random effects models. The results are expressed as binary risk, 95% confidence interval (CI), and relative risk (RR). The Mantel-Haenszel method and Z test were used to determine the overall results and determine the significance of the RR.. This study included 31 RCTs and 86,809 subjects. Compared with placebo, sacubitril/valsartan treatment significantly reduced the risk of new-onset DM among all patients (RR = 0.78, 95% CI: 0.64-0.95), patients with heart failure (HF) (RR = 0.24, 95% CI: 0.12-0.48), HF with reduced ejection fraction (HFrEF) (RR = 0.24, 95% CI: 0.12-0.50), and HF with preserved ejection fraction (HFpEF) (RR = 0.54, 95% CI 0.34-0.85). In contrast, sacubitril/valsartan treatment significantly increased the risk of hypoglycaemia among all patients (RR = 1.91, 95% CI: 1.05-3.47), patients with not all-DM (defined as part of the study population having DM at baseline) (RR = 5.71, 95% CI: 2.02-16.21), and patients with HFpEF (RR = 7.06, 95% CI: 2.10-23.76). Compared with ACEI/ARB, sacubitril/valsartan treatment significantly increased the risk of hypoglycaemia among patients with HF (RR 1.85, 95% CI 1.12-3.06, p = 0.02) and HFpEF (RR 3.59, 95% CI 1.51-8.55, p = 0.004). Compared with placebo, ACEI/ARB treatment did significantly reduce the risk of new-onset DM among all patients (RR 0.85, 95% CI 0.77-0.93, p = 0.0007) and patients with not all-HF (defined as part of the study population having HF at baseline) (RR 0.87, 95% CI 0.82-0.93, p<0.0001) and HFpEF (RR 0.60, 95% CI 0.44-0.83, p = 0.002), diabetes complications among patients with non-HF (/not all-DM) (RR 0.87, 95% CI 0.76-0.99, p = 0.04), and subsequent diabetes treatment among patients with new-onset DM (RR 0.70, 95% CI 0.58-0.84, p = 0.0002) and significantly increased the risk of hypoglycaemia among patients with not all-DM (RR 2.06, 95% CI 1.172-3.61, p = 0.01).. The results of our study, especially in reducing glycaemia and new-onset DM, revealed that sacubitril/valsartan had a positive effect on the control of glycaemia and the development of DM. ACEI/ARB also had a beneficial effect but the effect was weaker than that of sacubitril/valsartan. The above effects varied across diseases but the evidence was strongest in patients with HF.. CRD42022336311.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Diabetes Mellitus; Drug Combinations; Heart Failure; Humans; Hypoglycemia; Randomized Controlled Trials as Topic; Stroke Volume; Tetrazoles; Valsartan

Diabetes mellitus is associated with worse outcomes and lower attainment of disease-modifying therapies in patients with heart failure with reduced ejection fraction (HFrEF). This post hoc analysis of TRANSITION compared the patterns of tolerability and uptitration of sacubitril/valsartan in patients with HFrEF stabilized after hospital admission due to acute decompensated HF depending on the presence or absence of diabetes as a co-morbidity.. TRANSITION, a randomized, open-label study compared sacubitril/valsartan initiation pre-discharge vs. post-discharge (up to14 days) in 991 patients hospitalized for acutely decompensated HFrEF. The impact of diabetes status on tolerability and safety was studied at 10-week and 26-week post-randomization.. Among the 991 patients analysed at baseline, 460 (46.4%) had diabetes and exhibited a higher risk profile. At 10 weeks, sacubitril/valsartan target dose (97/103 mg bid) was achieved in a similar proportion of patients in each subgroup, when initiated pre-discharge or post-discharge respectively [diabetes subgroup: 47% (n = 105/226) vs. 50% (n = 115/228); relative risk ratio (RRR), 0.923; P = 0.412; non-diabetes subgroup: 45% (n = 119/267) vs. 51% (n = 133/261); RRR, 0.878; P = 0.155]. The proportions of patients achieving and maintaining either 49/51 mg or 97/103 mg bid [diabetes subgroup: 61.1% (n = 138/226) vs. 67.5% (n = 154/228); RRR, 0.909; P = 0.175; non-diabetes subgroup: 62.9% [n = 168/267] vs 69.3% [n = 181/261]; RRR, 0.906; P = 0.118] or any dose for ≥2 weeks leading to Week 10 [diabetes subgroup: 85% (n = 192/226) vs. 88.2% (n = 201/228); RRR, 0.966; P = 0.356; non-diabetes subgroup: 86.9% (n = 232/267) vs. 90.8% (n = 237/261); RRR, 0.963; P = 0.215] were also similar in each subgroup, when initiated pre-discharge or post-discharge, respectively. At 10 weeks, hypotension and renal dysfunction rates were similar, although hyperkalaemia was higher among patients with diabetes (15.9% vs. 9.5%). The rate of permanent discontinuation due to adverse events was similar in the diabetes and non-diabetes subgroups at 10 weeks, respectively: pre-discharge (7.5% vs. 7.1%) or post-discharge (5.7% vs. 4.2%). Similar patterns of uptitration and tolerability were observed at 26 weeks. Cardiac biomarkers including NT-proBNP (P < 0.005) and hs-TnT (P < 0.005) reduced significantly from baseline levels in both subgroups at Weeks 4 and 10; however, the response was greater among patients without diabetes. Mortality (diabetes vs. non-diabetes subgroups: 3.3% vs 4.0%; P = 0.438) and HF rehospitalization (diabetes vs. non-diabetes subgroups: 36.3% vs. 33.0%; P = 0.295) did not differ between the groups at 26 weeks.. Despite a higher risk profile among patients with diabetes, sacubitril/valsartan initiation either before or shortly after discharge in hospitalized patients with HFrEF resulted in comparable rates of dose up-titration and tolerability as in those without diabetes.

Topics: Aftercare; Aminobutyrates; Angiotensin Receptor Antagonists; Biphenyl Compounds; Diabetes Mellitus; Heart Failure; Humans; Patient Discharge; Stroke Volume; Tetrazoles; Valsartan

Guidelines classify sacubitril/valsartan as a significant part of medical treatment of heart failure with reduced ejection fraction (HFrEF). Data have shown that the HbA1c levels in patients with diabetes mellitus could be impacted by sacubitril/valsartan. A possible positive effect in diabetes patients treated with sacubitril/valsartan on outcome and echocardiography parameters is not well studied yet.. The aim of the present study was to compare the impact of sacubitril/valsartan on life-threatening arrhythmias, atrial fibrillation, different echocardiography parameters and congestion rate in patients suffering from HFrEF according to the diagnosis diabetes mellitus or no diabetes mellitus.. Consecutive 240 patients with HFrEF from 2016 to 2020 were treated with sacubitril/valsartan and separated to concomitant diabetes mellitus (n = 87, median age 68 years interquartile range (IQR) [32-87]) or no diabetes mellitus (n = 153, median age 66 year IQR [34-89]). Different comorbidities and outcome data were evaluated over a follow-up period of 24 months. Arterial hypertension (87% vs. 64%; P < 0.01) and coronary artery disease (74% vs. 60%; P = 0.03) were more often documented in patients with diabetes mellitus compared with patients without diabetes mellitus. Over the follow-up of 24 months several changes were noted in both subgroups: Median left ventricular ejection fraction (EF) increased significantly in non-diabetes (27% IQR [3-44] at baseline to 35% IQR [13-64]; P < 0.001), but not in diabetic patients (29% IQR [10-65] at baseline to 30% IQR [13-55]; P = 0.11). Accordingly, NT-proBNP and troponin-I levels decreased significantly in non-diabetes patients (NT-brain natriuretic peptide [NT-proBNP] from median 1445 pg/mL IQR [12.6-74 676] to 491 pg/mL IQR [13-4571]; P < 0.001, troponin-I levels from 0.099 ng/mL IQR [0.009-138.69] to 0.023 ng/mL IQR [0.006-0.635]; P < 0.001), but not in diabetic patients (NT-proBNP from 1395 pg/mL IQR [100-29 924] to 885 pg/mL IQR [159-4331]; P = 0.06, troponin-I levels from 0.05 ng/mL IQR [0.013-103.0] to 0.020 ng/mL IQR [0.015-0.514]; P = 0.27). No significant change of laboratory parameters e. g. glomerular filtration rate, potassium level and creatinine levels were found in diabetes or non-diabetes patients. Comparing further echocardiography data, left atrial surface area, right atrial surface area, E/A ratio did not show a significant change either in the diabetes or non-diabetes group. However, the tricuspid annular plane systolic excursion was significantly increased in non-diabetes mellitus patients (from 17 mm IQR [3-31] to 18 mm [2.5-31]; P = 0.04), and not in diabetic s patients (17.5 mm IQR [8-30] to 18 mm IQR [14-31]; P = 0.70); the systolic pulmonary artery pressure remained unchanged in both groups. During follow-up, a similar rate of ventricular tachyarrhythmias was observed in both groups. The congestion rate decreased significantly in both groups, in diabetes patients (44.4% before sacubitril/valsartan and 13.5% after 24 months treatment; P = 0.0009) and in non-diabetic patients (28.4% before sacubitril/valsartan and 8.4% after 24 months treatment; P = 0.0004). The all-cause mortality rate was. Sacubitril/valsartan reverses cardiac remodelling in non-diabetes patients. However, it reduces the congestion rate in diabetes and non-diabetes patients. The rates of ventricular tachyarrhythmias were similar in DM compared with non-DM over follow-up. The mortality rate remained to be over follow-up higher in diabetes patients compared with non-diabetes; however, it was lower compared with published data on diabetes and concomitant HFrEF not treated with sacubitril/valsartan.

Topics: Aged; Atrial Fibrillation; Diabetes Mellitus; Heart Failure; Humans; Stroke Volume; Tachycardia, Ventricular; Tetrazoles; Troponin I; Valsartan; Ventricular Function, Left

This study aimed to evaluate the efficacy of nifedipine controlled-release tablets combined with sacubitril valsartan in diabetic nephropathy (DN) patients with hypertension. One hundred and twelve DN patients with hypertension were enrolled. They were randomly divided into the control group (treated with nifedipine controlled-release tablets combined with valsartan) and the observation group (treated with nifedipine controlled-release tablets combined with sacubitril valsartan). Renal function, endothelial function and inflammatory response were examined. After three-months treatment, the levels of clinical indexes (glycosylated hemoglobin, fasting blood glucose, systolic and diastolic blood pressure), renal function indicators (urinary albumin excretion rate, blood urea nitrogen, serum creatinine and cystatin C), endothelial function indicators (microalbumin, angiotensin II, thrombomodulin and cartilage oligomeric matrix protein) and inflammatory response factors (interleukin-6 and tumor necrosis factor-α) in the observation group were significantly lower than those in the control group. Nifedipine controlled-release tablets combined with sacubitril valsartan could effectively alleviate the progression of DN combined with hypertension.

Topics: Biphenyl Compounds; Delayed-Action Preparations; Diabetes Mellitus; Diabetic Nephropathies; Drug Combinations; Humans; Hypertension; Nifedipine; Tetrazoles; Valsartan

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Biphenyl Compounds; Diabetes Mellitus; Drug Combinations; Heart Failure; Humans; Kidney; Stroke Volume; Tetrazoles; Valsartan; Ventricular Function, Left

Compared with enalapril, sacubitril/valsartan lowered HbA1c and reduced new insulin therapy in patients with heart failure with reduced ejection fraction (HFrEF) and diabetes in the PARADIGM-HF trial. We sought to assess the glycemic effects of sacubitril/valsartan in heart failure with preserved ejection fraction (HFpEF) and diabetes, and across the spectrum of left ventricular ejection fraction (LVEF) in heart failure and diabetes.. We compared the effect of sacubitril/valsartan, relative to valsartan, on HbA1c, new insulin therapy and hypoglycemia in the randomized controlled trial PARAGON-HF, and performed pooled analyses of PARAGON-HF and PARADIGM-HF.. Sacubitril/valsartan reduced HbA1c and new insulin therapy in patients with heart failure and diabetes across the spectrum of LVEF but may be associated with a slightly higher risk for hypoglycemia. Trial registration ClinicalTrials.gov NCT01920711.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Biphenyl Compounds; Blood Glucose; Diabetes Mellitus; Enalapril; Glycated Hemoglobin; Heart Failure; Humans; Hypoglycemia; Insulins; Stroke Volume; Tetrazoles; Valsartan; Ventricular Function, Left

HFrEF (heart failure with reduced ejection fraction) with a left ventricular ejection fraction of 25-30 % was detected in a 79-year-old man. For further treatment, inpatient cardiac rehabilitation war carried out.. At the start of the cardiac rehabilitation, patient complained of shortness of breath with little exertion, corresponding to NYHA III. Drug therapy included empagliflozin 10 mg, sacubitril/valsartan 24/26 mg, edoxaban 60 mg, torasemide 5 mg, verapamil 80 mg and amiodarone 200 mg.. The daily blood sugar profile showed hypoglycemia with values ​​< 3.7 mmol/l (< 67 mg/dl). After consultation with the patient, these occurred with normal food intake and were symptomatic in form of dizziness during the period of hypoglycaemia.. Symptomatic hypoglycaemia on SGLT2(sodium-glucose linked transporter 2)-inhibitor therapy in a patient with HFrEF without diabetes mellitus.. The therapy with empaglifozin was stopped and a new daily blood sugar profile was carried out, which no longer showed any hypoglycaemic values.. The presented case raises awareness of the side effect of hypoglycaemia, which occurs very rarely with SGLT2 inhibitors in studies in patients with HFrEF without the presence of diabetes mellitus.. Bei einem 79-jährigen wurde eine HFrEF (heart failure with reduced ejection fraction) mit einer linksventrikulären Ejektionsfraktion von 25–30 % nachgewiesen. Zur weiteren Behandlung wurde eine kardiologische Rehabilitationsmaßnahme durchgeführt.. Bei Antritt der AHB klagte der Patient über Luftnot bei geringer Belastung entsprechend dem Stadium NYHA III. Die medikamentöse Therapie beinhaltete Empagliflozin 10 mg, Sacubitril/Valsartan 24/26 mg, Edoxaban 60 mg, Torasemid 5 mg, Verapamil 80 mg sowie Amiodaron 200 mg.. Im Blutzucker-Tagesprofil zeigten sich Hypoglykämien mit Werten < 3,7 mmol/l (< 67 mg/dl). Nach Rücksprache mit dem Patienten traten diese unter normaler Nahrungsaufnahme auf und waren in Form von Schwindel im Zeitraum der Hypoglykämien symptomatisch.. Symptomatische Hypoglykämie unter SGLT2(sodium-glucose linked transporter 2)-Inhibitor-Therapie bei einem Patienten mit HFrEF ohne Diabetes mellitus.. Die Therapie mit Empagliflozin wurde beendet und ein erneutes Blutzucker-Tagesprofil durchgeführt – dieses zeigte keine hypoglykämischen Werte mehr.. Der hier vorgestellte Fall sensibilisiert für die unter SGLT2-Inhibitoren in Studien sehr selten auftretende Nebenwirkung der Hypoglykämie bei Patienten mit HFrEF ohne Vorliegen eines Diabetes mellitus.

Topics: Aged; Aminobutyrates; Biphenyl Compounds; Blood Glucose; Diabetes Mellitus; Drug Combinations; Heart Failure; Humans; Hypoglycemia; Male; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume; Tetrazoles; Ventricular Function, Left