Effects of Sacubitril/Valsartan Versus Telmisartan in Type 2 Diabetic or Pre-Diabetic Patients with Hypertension and Without Heart Failure: The Rationale and Design of A Randomized Clinical Trial

Abstract

Background: Sacubitril/valsartan has revealed superior glycemic and blood pressure control compared with enalapril and irbesartan in patients with heart failure and type 2 diabetes and in individuals with chronic kidney disease. However, whether the effects of sacubitril/valsartan remain the same in those without heart failure is unknown. Methods: A multicenter randomized double-blinded trial will be carried out in five military hospitals in Taiwan for a period of 1 year. Participants with prior cardiovascular diseases and heart failure will be excluded. The purpose of the study is to compare the effects of sacubitril/valsartan (97/103 mg once or twice daily) on the temporal changes in fasting blood glucose, HbA1c, insulin resistance and blood pressure levels with telmisartan (40 mg once or twice daily) in individuals with stage 1-3 hypertension and newly diagnosed type 2 diabetes or prediabetes who have an HbA1c ≥6.0% and a systolic blood pressure ≥130 mmHg or a diastolic blood pressure ≥85 mmHg. The inclusion criteria include the age of 35-70 years, women who are not pregnant, estimated glomerular filtration rate ≥45 ml/min per 1.73m2 and B-type natriuretic peptide levels <400 pg/ml. Results: The sample size is estimated to be 502 participants for randomization according to an assumption of between-person standard deviation in systolic blood pressure of 15 mmHg or in HbA1c of 1.5%, which provides ≥80% power (at p =0.05) to detect a difference in systolic blood pressure of 4 mmHg or in HbA1c of 0.3% at the final follow-up. All participants will receive a comprehensive physical examination and tests for blood cell counts, blood biochemistry, urine analysis, 12-lead electrocardiography and an echocardiography every 3 months. Conclusion: All analyses will be performed based on the intention-to-treat principle among all randomized participants.