Lecture on anti diabetic drugs

1. Antidiabetic drugs
Dr Hemant Kumar (Ph.D.)
Assistant Professor
Department of Pharmacology
FMHS, SGT University, Gurugram

2. Diabetes mellitus (DM)
It is a chronic metabolic disease characterized by elevated
levels of blood glucose, which leads over time to serious
damage to the heart, blood vessels, eyes, kidneys and
nerves (WHO).

3. Diagnosis of DM

4. HbA1c (Glycated haemoglobin)
A form of Hb that is chemically linked to a sugar
Indicates the presence of excessive sugar in the
bloodstream
HbA1c is measured primarily to determine the three-
month average blood sugar level

5. Type 1 DM Type 2 DM
Juvenile-onset DM- In
children and adolescents
Adult-onset DM- In middle-
aged and older adults
Autoimmune- destruction of
pancreatic beta- cells by
antibodies
insulin resistance and relative
insulin insufficiency
Poor life style and diet
Pancreatic beta- cells are not
sufficient to release required
insulin on stimulation
Required insulin is released
on stimulation of beta- cells
Insulin is used Other anti-diabetic drugs

6. Clinical manifestations of DM
Hyperglycemia
Excessive urination, thirst and weight loss
Complications of DM  Diabetic ketoacidosis
 Diabetic retinopathy
 Diabetic nephropathy
 Diabetic neuropathy

7. Classification of antidiabetic drugs
 Hypoglycemic agents
 Antihyperglycemic agents
• Act by releasing insulin
• May decrease blood glucose below normal level
• Risk of hypoglycemia
• Not act by releasing insulin but via some other mechanism
• Maintain blood glucose to normal level
• Minimal risk of hypoglycemia

8. Hypoglycemic agents classification
1) Insulin and its analogs
• Ultra-short acting
• Short acting
• Intermediate acting
• Long acting
• Ultra-long acting

9. Hypoglycemic agents classification cont..
2) Sulfonylureas
1st generation
Chlorpropamide
Tolbutamide
2nd generation
Glibenclamide (Glyburide)
Gliclazide
Glipizide
Glimepiride

10. Hypoglycemic agents classification cont..
3) Meglitinide analogues
Nateglinide
Repaglinide
4) GLP-1 analogs
• Oral
Semaglutide
• Parenteral
Exenatide
Liraglutide
5) DPP-4 inhibitors
Sitagliptin
Tenaligliptin
Vildagliptin
Saxagliptin
Alogliptin

11. Mechanism of insulin release
Sulfonylureas
Meglitinide analogs
Inhibit
Inhibit
Sulfonamides (cause hyperglycemia)

12. Action of insulin
1) Decrease blood glucose by
Stimulating the entry of glucose in muscle and fat (by
inceasing synthesis of GLUT- 4)
Inhibiting glycogenolysis and gluconeogenesis - at
low concentration
Increasing glycolysis and glycogenesis- at high
concentration

13. Action of insulin
2) Inhibits lipolysis and favours triglyceride deposition
3) Inhibits the breakdown of proteins and increases its
synthesis

14. Indications of insulin
1) Type- 1 DM (IDDM)
2) NIDDM
 In pregnancy
 Uncontrolled diabetes
 In complications like diabetes ketoacidosis
3) Acute hyperkalemia

15. Complications of insulin
1) Hypoglycemia- treated by Glucose (i.v.) or glucagon (i.v.)
2) Lipodystrophy at injection site
3) Edema due to Na+ and water retention (rare)

16. Drug interactions of insulin
1) Non-selective beta- blockers
2) Acute consumption of alcohol (can precipitate
hypoglycemia)
3) Drugs increasing glucose levels (corticosteroid, Oral
contraceptives, diuretics, diazoxide, etc.)

17. Sulfonylureas
1st generation
Chlorpropamide,
Tolbutamide
2nd generation
Glibenclamide , Gliclazide,
Glimepiride, Glipizide
More hypoglycemia
Less potent
Less preferred
Less hypoglycemia
More potent
More preferred
MOA: ATP- sensitive K+ channel inhibitor
cause depolarisation of β- cells
Release insulin

18. Second generation sulfonylureas
Glibenclamide/ Glyburide – Long acting
Maximum hypoglycemia
Gliclazide – additional antiplatelet action
Glimepiride
Glipizide

19. Miglitinide analogs: Nateglinide, Repaglinide
Act by releasing insulin
Orally active and short acting (3-4 times/ day)
Used to control post-prandial hyperglycemia (DOC)
MOA: Similar to sulfonylureas (SUs)
Stimulate insulin release by inhibiting ATP-sensitive
potassium channels of the β- cell membrane via
binding on a receptor distinct from that of SUs
ADR: Hypoglycemia and weight gain

20. Glucagon like peptide- 1 (GLP-1) analogs
Oral
Semaglutide
Parenteral (s.c.)
Exenatide
Liraglutide
Food in g.i.t. GLP Insulin release
GLP
analogs
 ADR: Nausea, vomiting, weight loss, acute pencreatitis

21. DPP-4 inhibitors
Sitagliptin
Tenaligliptin
Vildagliptin
Saxagliptin
Alogliptin
Food in g.i.t. GLP Insulin release
Dehydropeptidyl peptidase- 4
(DPP- 4)
Metabolise
DPP-4
inhibitors
Inhibit
No nausea and weight loss like GLP-1 analogs
ADR: Nasopharyngitis, acute pancreatitis

22. Hypoglycemic agents
Adverse effects/ contraindications/ precautions
• Hypoglycemia
• Beta- blockers are relatively contraindicated

23. Antihyperglycemic agents

24. Antihyperglycemic agents
Not act by releasing insulin but via some other mechanism/s
Minimal risk of hypoglycemia

25. Antihyperglycemic agents classification
1) Biguanides
Metformin
Phenformin
2) Thiazolidinediones
Pioglitazone
Rosiglitazone
3) α-glucosidase inhibitors
Acarbose
Miglitol
Voglibose
4) Dopamine D2 receptor agonist
Bromocriptine

26. Biguanides
Metformin (more megaloblastic anaemia)
Phenformin (more lactic acidosis)
Metformin – 1st line drug for type 2 DM
MOA:
AMPK (Adenosine monophospahte activated protein
kinase) activator
Other mechanisms

27. Thiazolidinediones
Pioglitazone
Rosiglitazone
MOA: (Proxisome proliferator activated receptor gamma
(PPAR- gamma) activator
 Reverse insulin resistance
 Hepatic function monitoring recommended due to
hepatotoxicity
 ADR: Weight gain, edema, plasma volume expansion
(should be avoided in CHF patients)

28. α- glucosidase inhibitors
Acarbose
Miglitol
Voglibose
Decrease carbohydrate absorption
Restore beta cell function and prevent new case of type
2 DM
Major adverse effect is flatulence (CI in inflammatory
bowel disease)

29. Dopamine D2 receptor agonist
Bromocriptine
Acts by central mechanism
Alter insulin resistance

30. Choice of initial glucose lowering agent
Based on level of hyperglycemia
Mild to moderate
(200- 250 mg/ dl) or
(11.1- 13.9 mmol/ l)
Respond well to single oral glucose
lowering agents
Severe
(> 250 mg/ dl) or
(> 13.9 mmol/ l)
Combination therapy
 Insulin can be used as an initial therapy in severe hyperglycemia
or in those who are symptomatic from the hyperglycemia

31. Q-1 DOC for type II DM ?
Q-4 DOC for type II DM pregnancy ?
Q-5 DOC for post-prandial hyperglycemia ?
Q-6 DOC for diabetic ketoacidosis ?
Q-2 DOC for uncontrolled DM ?
Q-3 DOC for hypoglycemia in pregnancy ?
A1- Metformin
A2- Insulin
A3- Glucose
A4- Insulin
A5- Nateglinide
A6- Insulin and I.V. fluids

32. Thank you