Tip 2 Diyabette GLP-1 ve GIP

 GLP-1 :

GLP-1 exerts its main effect by stimulating glucose-dependent insulin release from the pancreatic islets . It has also been shown to slow gastric emptying , inhibit inappropriate post-meal glucagon release , and reduce food intake

 GLP-1 exhibits a short half-life of one to two minutes due to N-terminal degradation by the enzyme dipeptidyl peptidase 4 (DPP-4). Synthetic GLP-1 receptor agonists are variably resistant to degradation by the enzyme DPP-4, and therefore have a longer half-life, facilitating clinical use.

 

GIP :  In the postprandial state, GIP is cosecreted with GLP-1, and they appear to interact in an additive fashion to potentiate glucose-induced insulin secretion . However, GIP exhibits different effects than GLP-1 on glucagon secretion. In the euglycemic or hypoglycemic states, GIP enhances glucagon activity

 

 Combination with oral agents – GLP-1 receptor agonists can be combined with metformin and most other oral agents. They should not be combined with DPP-4 inhibitors, as there do not appear to be additive effects on glucose lowering .There are few trials directly evaluating the combination of GLP-1 receptor agonists with SGLT2 inhibitors, and the published trials are generally short-term with A1C as the primary outcome.

Combination with insulin – GLP-1 receptor agonists may be combined with insulin.  

Dual-acting GLP-1 and GIP receptor agonists – Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist. It appears to have remarkable glycemic (and weight-reducing) efficacy compared with either agent alone . It has been studied for use as monotherapy in patients inadequately treated with diet and exercise , as well as in combination with other agents, including metformin, sulfonylureas, and insülin glarjin.

Oral GLP-1 receptor agonist (orforglipron):

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are highly effective for the treatment of type 2 diabetes, but the inconvenience of administration limits use for some patients.After 26 weeks, orforglipron doses ≥12 mg daily led to greater mean reduction in A1C than placebo or dulaglutide.

 

 

 Triple Agonist :(GLP-1,GIP VE glukagon reseptör agonisti)

Retatrutide is a triple glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon receptor agonist in development for the treatment of type 2 diabetes.

 After 24 weeks, retatrutide led to greater mean reduction in A1C than placebo or dulaglutide (-2.02 percentage points with 12 mg retatrutide versus -0.01 and -1.41 percentage points with placebo and dulaglutide, respectively). After 36 weeks, mean body weight loss with 12 mg retatrutide was 17.2 kg. Triple agonist therapy is a promising strategy for the treatment of type 2 diabetes.