Insulin sensitizers

insulin sensitisers

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

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

3. Overview

4. Insulin Sensitisers 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. Insulin sensitizers

6. Metformin mechanism of action

7. Pharmacokinetics

8. Clinical use 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. Adverse effects Immediate Nausea Metallic taste Anorexia Flatulence Diarrhoea Long term Megaloblastic anaemia Lactic acidosis - Rare

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

11. Advantages No insulin release , No hypoglycaemia Causes weight reduction in obese patients Lowers LDL and VLDL Elevates HDL

12. Thiazolidinediones [ glitazones ]

13. Thiazolidinedione mechanism of action

14. Why was pioglitazone withdrawn?? 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. Pharmacokinetics

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

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

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

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