Table 1.
Notable FDA-approved drugs, physiological effects, and cardiovascular clinical trials of drugs targeting the β-adrenergic, angiotensin II type 1, and incretin receptors.
| Receptor Activity | Proximal Effectors | FDA-approved Agents | Cardiovascular Effects | Notable Clinical Trials |
|---|---|---|---|---|
| β-adrenergic
receptors (β1AR and β2AR) antagonists |
Gαs,
Gαi, β -arrestin 1/2 |
Beta blockers: Acebutolol, Atenolol, Betaxolol, Bisoprolol, Carvedilol, Labetalol, Metoprolol, Nadolol, Nebivolol, Pindolol, Propranolol, Timolol | - Heart rate control - Negative inotropy - Reduction in myocardial oxygen demand - Reduces BP - Treatment of heart failure |
Heart Failure with Reduced Ejection
Fraction: 1993: Metoprolol in Dilated Cardiomyopathy (Metoprolol)53 1996: US Carvedilol HF Study (Carvedilol)54 1999: MERIT-HF (Metoprolol)56 1999: CIBIS-II (Bisoprolol)55 2001: COPERNICUS (Carvedilol)57 |
| Angiotensin II Type 1 Receptor (AT1R) antagonists |
Gαq,
Gαi, β -arrestin 1/2 |
ACE-I: Benazepril, Captopril,
Enalapril, Fosinopril, Lisinopril, Moexipril, Perindopril, Quinapril,
Ramipril, Transolapril ARB: Candesartan, Eprosartan, Irbesartan, Losartan, Olmesartan, Telmisartan, Valsartan |
- Reduces BP - Treatment of heart failure - Renoprotection by decreasing glomerular filtration |
Heart Failure with Reduced Ejection
Fraction: 1987: CONSENSUS (Enalapril)157 1991: V-HeFT II (Enalapril)252 1991: SOLVD-T (Enalapril)253 1992: SOLVD-P (Enalapril)254 1997: ELITE (Losartan / Captopril)158 2001: Val-HeFT (Valsartan)255 2003: CHARM-Alt (Candesartan)256 2014: PARADIGM-HF (Sacubitril-Valsartan / Enalapril)159 |
| Glucagon-like peptide 1 receptor (GLP-1R) agonists |
Gαs, Gαq,
Gαi, β -arrestin 1 |
Dulaglutide, Exenatide, Liraglutide, Lixisenatide, Tirzepatide (dual GLP-1R and GIPR agonist) | - Weight loss - Glycemic control - Reduction in major cardiovascular events - Improvement in heart failure |
Major adverse cardiovascular events
(Nonfatal myocardial infarction, nonfatal stroke, or cardiovascular
death): 2021 Meta-analysis of eight clinical trials in diabetes (Lixisenatide, Liraglutide, Semaglutide, Exenatide, Albiglutide, Dulaglutide, Efpeglenatide)172 2023 SELECT – Obesity and CAD without diabetes (Semaglutide)173 Heart Failure with Preserved Ejection Fraction: 2023 STEP-HFpEF – Obesity without diabetes (Semaglutide)174 |