What is the research question? Semaglutide and tirzepatide cause weight loss and blood pressure reduction. However, weight loss only partially explains the blood pressure reduction. Based on previous studies, there might be direct effects in the cardiovascular system. In forearm blood flow studies, semaglutide and tirzepatide will be infused into the brachial artery to investigate their effects on the function of blood vessels. In systemic studies, semaglutide and tirzepatide will be infused into systemic circulation to investigate their effects on heart and blood vessels.
There are three different populations being looked at for this study: participants with normal weight and normal blood pressure, participants with obesity and normal blood pressure, and participants with obesity and high blood pressure.
There are six sub-studies each with different visit schedules. The minimum participant study duration (including follow-up phone call) would be 2 days, while the maximum participant study duration would be approximately 2 - 2.5 months. The overall study duration is expected to be approximately 18 months.
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)
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)
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Treatment groupsSee each treatment group below.