Insulin secretagogues are medications that enhance insulin secretion from the pancreas and are primarily used in treating Type 2 diabetes. There are several classes, including sulfonylureas, glinides, GLP-1 analogues, and DPP-4 inhibitors, each with unique mechanisms of action and associated adverse effects. Key concerns with these drugs include weight gain, hypoglycemia, and various other risks, including potential cancer links and teratogenic effects.

1. Insulin Secretagogues
Bilal Sami Al-Mosheqah

2. Learning Objectives
Insulin Secretagogues
Main Adverse Effect
Mechanism of Action
Classification

3. Insulin Secretagogues
Definition
Are drugs which increase the amount of insulin secreted by the pancreas
Types
Sulfonylureas
Glinides
GLP-1
DPP-4 Inhibitor
Modulators of Incretins
GLP-1:Glucagon like peptide one / DPP-4: dipeptidyl peptidase 4
Potassium Channel blocker
Widely used in treatment of diabetes type 2

4. Sulfonylureas
Examples 1st generation 2nd generation 3rd generation
Glybenclamide
Tolbutamide Glimepiride
Not used as much
anymore !
Mechanism of Action(MOA)
Pancreatic action Insulin release 2 phases
Safe in pregnancy ! Safe in renal patient !

5. Mechanism of Action
ATP
K+(closes,
depolarizes)
Sulphonylureas
Glinides
-
Ca2+
Ca2+

6.  Peripheral glucose uptake
 Upregulation of insulin receptors
Sulfonylureas
Extra-pancreatic action
2nd , 3rd
In peripheral tissue :
Liver :  Gluconeogenesis
 Metabolism of insulin

7. Main Adverse Effect
Sulfonylureas
The over all action is to increase insulin and decrease its degradation
Weight gain Hyperinsulinemia Hypoglycemia
Not favourable in
obese patient
Other Adverse Effect Teratogenic
Not glibenclamide
Sulfa allergy
Around 3% of people

8. Glinides
Examples Repaglinides , Nateglinides
MOA Potassium channel blocker (Same as SU)
Main Adverse Effect Weight gain Hypoglycemia
Less than SU
But they have Rapid onset and short duration
Postprandial glucose modulator
Phase 1 insulin secretion

9. GLP-1 Analogue
Examples Exenatide , Liraglutide
MOA Mimic the action of incretin (incretin analogue)

14. Examples Exenatide , Liraglutide
MOA Mimic the action of incretin (incretin analogue)
But more powerful.(WHY!)
Main Adverse Effect
Hypoglycemia (not alone) Weight loss
HOW?
Thyroid and pancreatic cancer
Pancreatitis
GLP-1 Analogue
GIT: N 40% , V 15%
In animals

15. Gliptins
Examples
MOA
Main Adverse Effect
Sitagliptin, Saxagliptin
Inhibit the degradation of GLP-1
Hypersensitivity: acute pancreatitis Increase risk of infection
Hypoglycemia (not alone)
Nasophryngitis
Sinusitis
URTI ,UTI
Pancreatic cancer in animals

16. Summary
 Insulin Secretagogues are Widely used in treatment of diabetes type 2
 It consist of different families : SU , Glinides , Incretin analogue and DPP4 inhibitor
 It increases Insulin secretion by different pathways

17. Any Question

18. Reference
Karen Whalen; Carinda Feild; Rajan Radhakrishnan (2019) Lippincott's
illustrated reviews, 7th edn., Philadelphia: Wolters Kluwer.
Brian K Alldredge ( 2013) Applied therapeutics the clinical use of drugs, 10th edn.,
Philadelphia: Philadelphia Wolters Kluwer/Lippincott Williams & Wilkins c.