DECODE - Haemodynamic Effects Of Semaglutide and Tirzepatide - a Series of Pilot Studies

Inclusion Criteria: 1. Inclusion Criteria - Participants with normal weight and normal blood pressure * Have given written informed consent to participate * Aged 18 to 50 years (inclusive) * Females must be post/peri-menopausal or if of child-bearing potential they are required to use adequate contraception and to have a negative pregnancy test (performed at each visit) * Current non-smoker * Body mass index (BMI) in range 18.5-24.9 kg/m2 * Clinic brachial systolic blood pressure \<140 mmHg and diastolic blood pressure \<90 mmHg 2. Inclusion Criteria - Obese participants with normal blood pressure * Have given written informed consent to participate * Aged 18 to 50 years (inclusive) * Male or female * Females must be post/peri-menopausal or if of child-bearing potential they are required to use adequate contraception and to have negative pregnancy test (performed at each visit) * Current non-smoker * BMI ≥30 kg/m2 * Clinic brachial systolic blood pressure \<140 mmHg and diastolic blood pressure \<90 mmHg 3. Inclusion Criteria - Obese participants with high blood pressure * Have given written informed consent to participate * Aged 18 to 50 years (inclusive) * Male or female * Females must be post/peri-menopausal or if of child-bearing potential they are required to use adequate contraception and to have negative pregnancy test (performed at each visit) * Current non-smoker * BMI ≥30 kg/m2 * Diagnosis of stage 1 essential hypertension Exclusion Criteria: * Regular use of medications with vasoactive or cardiac effects in normotensive individuals; inability or unwillingness to omit anti-hypertensive medications on the morning of the study visits in hypertensive individuals * Hypersensitivity to any of the study drugs or excipients * Known clinically significant valvular heart disease * Implanted pacemaker or implantable cardioverter defibrillator (ICD) * Known active malignancy * Known renal impairment (creatinine \>150µmol/L) * Clinically significant neurological disease * History of scleroderma * Current pregnancy, breastfeeding * Current involvement in the active treatment phase of other research studies (excluding observational/non-interventional) * Second or third-degree AV block, sino-atrial block, sick sinus syndrome * Known HIV, hepatitis B or C * Needle phobia * Participants treated with formal anticoagulant therapy such as, but not limited to, heparin or warfarin * Diagnosis of Type 1 or Type 2 Diabetes Mellitus or current usage of insulin or other injectable drugs for the treatment of diabetes such as but not limited to GLP-1 and GIP receptor agonists * BMI \<18.5 kg/m2 * Known heart failure * Currently taking drugs likely to have interactions with semaglutide or tirzepatide * Family history of multiple endocrine neoplasia * Known thyroid cancer * Known history of pancreatitis * History of gall stones (unless the gall bladder has been removed) * Any other clinical reason which may preclude entry in the opinion of the investigator