This document summarizes insulin sensitizers, including their mechanism of action, pharmacokinetics, uses, adverse effects, and drug interactions. It focuses on the biguanides metformin and phenformin, and the thiazolidinediones pioglitazone and rosiglitazone. Metformin works by decreasing insulin resistance and is the first-line treatment for type 2 diabetes. Pioglitazone increases insulin sensitivity but requires careful use due to risks of weight gain, hepatotoxicity, and rare reports of bladder cancer. Both classes improve blood glucose control and have similar advantages, though individual drugs have distinct absorption, metabolism, and side effect profiles that require consideration.

1. DR.VIRAJ A. SHINDE
JR1
DEPARTMENT OF PHARMACOLOGY
GMC NAGPUR

2.  What are insulin sensitizers ??
 Pharmacology of biguanides
 Pharmacology of thiozolidinediones

3. • DefinitionInsulin sensitizers
• Mechanism of action
• Pharmacokinetics , uses, adverse effects
• Drug interactions
• Advantages
Metformin
• Mechanism of action
• Pharmacokinetics
• Uses , adverse effects
• Drug interactions
Thiazolidinediones

4. Drugs that improve action of insulin and
generally result in lowering in levels of
insulin and blood glucose levels in patients
with insulin resistance

5. • Metformin
• PhenforminBIGUANIDES
• Pioglitazone
• RosiglitazoneTHIAZOLIDINEDIONES

7. Absorption- small intestine
t1/2 - 2 to 3 hrs
Duration of action – 6 to 10 hrs
Not protein bound
Not metabolised
Excreted unchanged in urine

8.  First line drug for type 2 DM
 Decrease insulin resistance
 In combination with other Oral hypoglycemic
agents
 Decreases micro as well as macro vascular
complications
 Non diabetic use - Polycystic ovarian disease
( PCOD)

9. Immediate
 Nausea
 Metallic taste
 Anorexia
 Flatulence
 Diarrhoea
Long term
 Megaloblastic
anaemia
 Lactic acidosis - Rare

10. Eliminated by renal tubular secretion
 Cimetidine
 Furosemide
 Nifedipine
Dose reduction of Metformin

11. 1. No insulin release , No hypoglycaemia
2. Causes weight reduction in obese patients
3. Lowers LDL and VLDL
4. Elevates HDL

12. •Withdrawn in june
2013
•Reintroduced in july
2013
Pioglitazone
•withdrawn
•Due to MI and Other
cardiovascular
events
Rosiglitazone

14.  Association with bladder cancer
 Reintroduced With box warnings
1) not to be prescribed in
2) Safety and efficacy to be reviewed after 3-6
months of starting treatment
3) Risk factors of bladder cancer should be
assessed a) Age
b) Current and past h/o smoking
c) Occupational history
d) Chemotherapy history
e) Previous irradiation to pelvic region
4) Use with extra care in elderly patient

15. Absorption in 2 -3 hrs
Duration of action 24hrs
Metabolised in liver
By cytochrome enzyme (CYP 2C8
& CYP3A4 )

16.  Increases insulin sensitivity and decreases
insulin resistance in type 2 DM
 Decreases HbA1C
 Increases HDL-C and decreases triglyceride
levels

17.  Weight gain
 Hepatoxicity - Rare
Contraindications
1)hepatic failure
2)pregnancy
3)lactating mothers
4)children
5)heart failure

18.  Rifampicin –
 Gemfibrozil -
Increase in dose of
pioglitazone
Redution in dose of
pioglitazone

19.  Metformin is first choice of drug in treating
type 2 dm due to its safety profile
 Pioglitazone should used as add on drug
after metformin and sulfonylureas

20.  Goodman and Gilman 12th edition, The
pharmacological basis of therapeutics
 S K Sharma 2nd edition, Principles of
pharmacology
 Pharmacovigilance programme of India
newsletter 6th august 2013 issue vol -3