Table 3.
Existence of clinical evidence supporting the MoA of QW GLP‐1 RAs
| Clinical effect (MoA) | Exenatide ER | Dulaglutide | Semaglutide |
|---|---|---|---|
| Glycaemic control (pancreatic α‐ and β‐cells a ) | Yes 37 , 39 , 40 , 41 , 49 , 55 | Yes 42 , 44 , 45 , 50 , 52 | Yes 46 , 49 , 50 |
| Body weight reductions (GI tract, brain, fat cells a ) | Yes 37 , 39 , 40 , 41 , 49 , 55 | Mixed 42 , 44 , 45 , 50 | Yes 46 , 49 , 50 |
| CV benefits (MoA undetermined a ) | No (non‐inferior to placebo for MACE; superiority not demonstrated) 71 | Yes 72 | Yes 17 |
| Systolic blood pressure reductions (brain a ) | Yes 37 , 40 , 41 , 49 , 77 | Mixed 42 , 44 , 45 , 52 | Yes 46 , 49 , 50 |
| Heart rate increases (muscle a ) | Yes 40 , 49 | Yes 42 , 44 , 45 , 52 | Yes (but not always statistically significant) 46 , 49 , 50 |
| Lipid lowering (fat cells a ) | Yes (but not always statistically significant) 37 , 40 , 41 | Yes 42 , 45 , 52 | Mixed 49 , 50 |
| Renal benefits (kidney a ) | Unclear 71 | Yes 52 , 72 , 85 | Yes 17 |
Abbreviations: CV, cardiovascular; ER, extended‐release; GI, gastrointestinal; GLP‐1 RA, glucagon‐like peptide‐1 receptor agonist; MACE, major adverse CV events; MoA, mechanisms of action; QW, once‐weekly; α, alpha; β, beta.
a
Cell types targeted by the MoA of GLP‐1 RAs as described in DeFronzo's ominous octet. 5