Semaglutide is GLP-1 receptor agonist, while tirzepatide is a "dual" agonist that also targets the GIP hormone. We are often asked to explain the differences.
GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide) are two incretin hormones that are released from the gut in response to food intake. Both hormones play a role in regulating blood sugar levels and appetite.
However, there are some key differences between GLP-1 and GIP.
GLP-1
- Produced by L cells in the distal ileum and colon
- Stimulates insulin secretion from the pancreas
- Inhibits glucagon secretion from the pancreas
- Slows gastric emptying
- Reduces appetite
- Increases satiety
GIP
- Produced by K cells in the duodenum and jejunum
- Stimulates insulin secretion from the pancreas
- Enhances fat storage
GIP is the main incretin hormone in healthy people, but its insulinotropic effect is reduced in people with type 2 diabetes. GLP-1, on the other hand, remains effective in people with type 2 diabetes.
GLP-1 also has a number of other beneficial effects, such as protecting beta cells from apoptosis and stimulating beta-cell proliferation.
Due to its superior insulinotropic effects and other beneficial effects, GLP-1 is considered to be a more promising target for the development of new diabetes treatments.
Here is a table that summarizes the key differences between GLP-1 and GIP:
| Characteristic | GLP-1 | GIP |
|---|---|---|
| Source | L cells in the distal ileum and colon | K cells in the duodenum and jejunum |
| Effects on insulin secretion | Stimulates | Stimulates |
| Effects on glucagon secretion | Inhibits | No effect |
| Effects on gastric emptying | Slows | No effect |
| Effects on appetite | Reduces | No effect |
| Effects on satiety | Increases | No effect |
| Effectiveness in type 2 diabetes | Remains effective | Reduced effectiveness |
| Other beneficial effects | Protects beta cells from apoptosis, stimulates beta-cell proliferation | Enhances fat storage |
There are new medications in this category under development that will target 3 receptors, likely improving the effectiveness beyond what we are currently seeing with tirzepatide.