A Study on the Efficacy and Safety of Empagliflozin in the Treatment of Pulmonary Arterial Hypertension

Inclusion Criteria:

1. At least 18 years old.

2. Sign the informed consent form.

3. Subjects who are willing and able to comply with the requirements of prescribedvisits, treatment plans, laboratory examinations and other research procedures.

4. PAH with symptoms was initially diagnosed and belonged to one of the followingsubgroups: A. Idiopathic pulmonary hypertension (IPAH); B. hereditary pulmonary hypertension (HPAH); C drug or toxin-induced PAH, based on previous exposure to drugs, chemicalsor toxins, such as fenfluramine derivatives, other appetite suppressants, toxicrapeseed oil or L- tryptophan. D. PAH is accompanied by: A) connective tissue disease B) Congenital systemic-pulmonary shunt (surgicalcorrection must be performed at least one year before screening, and there is no orno clinically insignificant systemic-pulmonary shunt [1.0≤ lung-systemic blood flowratio (QP/QS)≤1.5]), according to the opinion of the researcher.

5. Received right heart catheterization (RHC) at the time of screening or within 5years before screening (if RHC is not performed, it will be performed duringscreening), which is consistent with the diagnosis of PAH and meets all thefollowing criteria: A. mean pulmonary artery pressure (papm) > 20mmhg (at rest) B pulmonary arteriolewedge pressure (PAWP)≤15 mmHg (if reliable PAWP data cannot be obtained, leftventricular end diastolic pressure [LVEDP]≤15 mmHg). C pulmonary vascular resistance (PVR) > 2.00 wood units (> 160 dynes/sec/cm5).

6. There are symptoms of WHO/NYHA FC Grade II or III.

7. Stable PAH targeted background oral therapy. Subjects received endothelin receptorantagonist (ERA) and/or phosphodiesterase inhibitor type 5 (PDE5-I) or solubleguanylate cyclase (sGC) agonist. Stability was defined as no change in dose orregimen within 30 days before baseline and during the duration of the study.

8. 6-minute walking distance (6 MWD) ≥ 150m.

9. If the subject is taking concomitant drugs that can affect PAH (for example, calciumchannel blockers, digoxin or L- arginine supplements), the dose must be kept stablefor at least 30 days before the baseline visit and throughout the study.

10. If there is the possibility of pregnancy, both male and female subjects should agreeto use a highly effective contraceptive method during the whole study period (frominformed consent to the end of follow-up).

Exclusion Criteria:

• 1. Subjects shall not have the following three or more risk factors for leftventricular dysfunction: Body mass index (BMI)≥30 kg/m2 History of systemichypertension

There is any of the following evidence to prove the history of major coronary artery disease:

A coronary angiographic evidence of a history of myocardial infarction or percutaneous coronary intervention or coronary artery disease (at least one coronary artery stenosis > 50%); B. Positive results of exercise provocation test and image evidence; C. previous coronary artery bypass surgery; D. stable angina pectoris; 2) Pulmonary function tests (PFTs) conducted within 180 days before or during the screening showed mild or above lung diseases. Subjects who meet any of the following criteria will be excluded: A. forced expiratory volume in the first second (FEV1)<60% (expected value); or B total lung volume (TLC) < 60% of the estimated value. 3) The evidence of thromboembolic disease is confirmed by lung ventilation/perfusion (V/Q) scanning or local standard diagnosis and treatment evaluation at the time of diagnosis or after diagnosis of PAH.

4. Severe chronic liver disease (i.e. Child-pugh grade C), portal hypertension, cirrhosis or complications of cirrhosis/portal hypertension (e.g., history of varicose bleeding, history of hepatic encephalopathy).

5. Confirm the active infection of hepatitis B virus (HBV) or hepatitis C virus (HCV).

6. Subjects whose alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level is more than or equal to 3 times the normal upper limit value (ULN) or whose total bilirubin is more than or equal to 2 times ULN at the time of screening.

7. Chronic renal insufficiency at screening, which is defined as serum creatinine > 2.5 mg/dL or requiring dialysis support.

8. Hemoglobin concentration < 9 g/dL during screening. 9) diabetes. 10) cardiac function grade IV (NYHA classification) 11) The subject has been treated with IV or SC prostacyclin pathway drugs (for example, epoprostol, triprostinil or iloprost) at any time before baseline (allowed to be used in pulmonary vasodilation test).

9. The subject has pulmonary vein occlusion disease. 13) Diagnosed and/or treated with malignant tumor within 5 years before screening, but excluding localized non-metastatic basal cell carcinoma or squamous cell carcinoma of the skin, or radical resection of cervical carcinoma in situ.

10. At the time of screening, there was a history of alcohol or drug abuse within 6 months.

11. Start the exercise-based cardiopulmonary rehabilitation program within 90 days of the screening period and/or during the study period.

12. Participated in other interventional clinical studies within 30 days before screening. It is allowed to participate in registered or observational studies at the same time, as long as the subjects meet all other selection criteria and comply with all research process requirements.

13. Any reason (for example, any past or intermittent diseases) that the respondent thinks may increase the risk of participating in the study or may affect the study analysis and damage the study participation or collaboration, so that the subject cannot participate in the study.

14. Those who are known to be allergic to Engelgin or any auxiliary materials. 19) According to the researcher's judgment, life expectancy is less than 12 months.

15. Pregnant or lactating women.