Sacubitril/Valsartan Treats Patients With Essential Hypertension and Type 2 Diabetic Nephropathy

Inclusion Criteria:

• Age 18 years or older, no gender restriction;

• Diagnosed with mild to moderate primary hypertension (140 ≤ SBP < 180 mmHg and/or 90 ≤ DBP < 110 mmHg), including newly diagnosed or inadequately treated patients (thosewho have not followed previous medical advice and have uncontrolled blood pressureaccording to the investigator);

• Diagnosed with type 2 diabetes (according to Guideline for the prevention andtreatment of type 2 diabetes mellitus in China (2020 edition)), and meeting thefollowing conditions: a) Continuously on ≥ 1 glucose control medication regimens (which may include long-acting insulin) for at least 12 weeks before screening, witha stable treatment regimen (i.e., the same medication and dosage) for at least 28days before screening, and maintaining this regimen during the study. At theinvestigator's discretion, the dose of supplemental short-acting insulin can beadjusted as needed to achieve adequate glucose control; b) HbA1c level ≤ 10.5% andfasting (≥ 8 hours) plasma glucose level ≤ 13.3 mmol/L (if fasting glucose > 13.3mmol/L, the investigator may repeat the test to determine eligibility);

• Urine albumin/creatinine ratio (UACR) ≥ 30 mg/g in two measurements taken onseparate days or eGFR < 60 mL/min/1.73 m²;

• Non-pregnant or fertile patients (male or female) using reliable contraception;

• Female patients with potential for pregnancy must have a negative pregnancy test atscreening;

• Subjects must voluntarily agree to comply strictly with the study protocolrequirements and sign a written informed consent form.

Exclusion Criteria:

• Presence of severe hypertension, malignant hypertension, hypertensive emergencies,or hypertensive crises;

• History or evidence of secondary hypertension within 12 months before screening,including but not limited to any of the following: renovascular hypertension, renalparenchymal hypertension, unilateral or bilateral renal artery stenosis, coarctationof the aorta, primary aldosteronism, Cushing's disease, pheochromocytoma, polycystickidney disease, and drug-induced hypertension;

• History of angioedema (drug-related or other causes) within 12 months beforescreening;

• Presence of diabetic ketoacidosis;

• History or evidence of secondary diabetes within 12 months before screening,including but not limited to any of the following: endocrine disorders causingcarbohydrate metabolism disorders, pancreatogenic diabetes, hepatogenic diabetes,nephrogenic diabetes, etc.;

• History of malignancy in any organ system (excluding localized basal cell carcinomaof the skin);

• History of acute stroke, lacunar infarction, or dementia within 6 months beforescreening;

• History of coronary artery bypass graft surgery or any percutaneous coronaryintervention (PCI) within 6 months before screening;

• Previously diagnosed or currently diagnosed heart failure (NYHA Class III-IV) orclinically significant valvular heart disease;

• History or current diagnosis of cardiac abnormalities: (1) second or third-degreeatrioventricular block without a pacemaker; (2) clinically significant arrhythmias,including atrial fibrillation with a ventricular rate ≥ 120 bpm; (3) family historyof long QT syndrome or torsades de pointes ventricular tachycardia;

• Chronic kidney disease stage 4 or higher (eGFR < 30 mL/min/1.73 m²), receiving renaldialysis, or history of kidney transplantation;

• Significant abnormalities in laboratory tests, such as potassium levels > 5.5 mmol/Lor < 3.5 mmol/L, sodium levels < 130 mmol/L, liver function (ALT, AST) results > 3times the upper limit of normal;

• History of allergy to antihypertensive drugs such as ARBs, Angiotensin-ConvertingEnzyme (ACE) inhibitors, or renin inhibitors;

• Clear history of intolerance to drugs similar to the study medication (e.g., ACEinhibitors, ARBs);

• Use of traditional Chinese or Western medicines that could affect the study'sefficacy during the study period (see appendix for list);

• Any surgery or medical condition that significantly alters the absorption,distribution, metabolism, or excretion of any medication, including but not limitedto the following: clinically significant gastrointestinal surgery within 12 monthsbefore the screening (e.g., gastrectomy, gastrointestinal anastomosis, bowelresection, gastric bypass, gastroenterostomy, or gastric banding), current activeinflammatory bowel disease or history of active inflammatory bowel disease;

• Pregnant or breastfeeding women, or patients of childbearing potential unwilling orunable to use effective contraception during the study period;

• Participation in another clinical study using any investigational drug orobservational study within 30 days before screening;

• Other conditions that, in the investigator's judgment, may affect the conduct of theclinical study or the determination of study results.