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

Prior treatment

• Participants treated with formal anticoagulant therapy such as, but not limited to, heparin or warfarin
• Currently taking drugs likely to have interactions with semaglutide or tirzepatide

Other illness

• 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
• Known active malignancy
• Clinically significant neurological disease
• History of scleroderma
• Second or third-degree AV block, sino-atrial block, sick sinus syndrome
• Known HIV, hepatitis B or C
• 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
• Known heart failure
• Family history of multiple endocrine neoplasia
• Known thyroid cancer
• Known history of pancreatitis
• History of gall stones (unless the gall bladder has been removed)

Lab values

• Known renal impairment (creatinine \>150µmol/L)

Other

• Implanted pacemaker or implantable cardioverter defibrillator (ICD)
• Current pregnancy, breastfeeding
• Current involvement in the active treatment phase of other research studies (excluding observational/non-interventional)
• Needle phobia
• BMI \<18.5 kg/m2
• Any other clinical reason which may preclude entry in the opinion of the investigator

• 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
• 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
• 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