sacubitril and Hypoglycemia

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

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