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Newer antidiabetic agents
1. Dr. Prerna Singh
Junior Resident 3rd year
Department of Pharmacology
JNMCH, AMU
Newer Antidiabetic Agents
2. INTRODUCTION
Diabetes mellitus refers to a group of metabolic
disorders that share a common phenotype of
hyperglycemia
-Harrison’s Principles of internal medicine
4types-
Type 1- IDDM
Type 2 -NIDDM
Type 3- Other specific types
Type 4 – Gestational DM
Insulin was the first peptide
hormone discovered.
Frederick Banting and Charles Herbert
Best, working in the laboratory of J.J.R.
Macleod at the University of Toronto,
were the first to isolate insulin from dog
pancreas in 1921.
7. New insulins
Detemir:
• Long acting: DOA <24 Hour
• Onset: 1-2 hour
• Less frequent hypoglycemia
• Minimum weight gain
Degludec :
• Long acting DOA>24 hour; 3times a week
8. New insulins
Neutral protamine lispro:
• Intermediate acting
• Reported more weight gain and hypoglycemia
HIM-2:
• In phase 3 trails
• Oral insulin
• Enhanced stability and resistance to intestinal degradation
9. New insulins
Oral insulin spray:
• In Phase 3 trial
• Liquid aerosol mist
• Absorbed through mucus membrane
10. New insulins
Bioavailability – 20%
Patient training is important
Exubera:
• Withdrawn in 2007 because of pulmonary fibrosis and risk of lung cancer
Afrezza:
• Approved In 2014
• Rapid acting inhaled insulin
• Not suitable for ketoacidosis
Side effect: Hypoglycemia, cough, throat pain and irritation
11. New insulin delivery system
• Pen device
• Insulin pump
• Continuous SC insulin infusion
13. Incretin based therapy
• Incretin: GI hormone
• Released after meal; increase insulin biosynthesis and release
• Examples: GLP1,GIP
• Metabolized by DPP IV- short half life
• DPP IV resistant GLP1 agonist are useful for therapy
• DPP IV inhibitor are useful for therapy
14. • Increase glucose dependent insulin secretion
• Control PP
• Show good efficacy as monotherapy but are not first line agents
• Used as adjuvant
Incretin mimetics
Exenatide (5-10mcg BD), Liraglutide (0.6-1.8mg OD), Albiglutide (30-50 mg weekly), Semaglutide
(oral)
15. Mechanism of action:
• Act on GLP1 receptor (GPCR)
• Activate cAMP-PKA pathway and also signaling via PKC & PI3K
• Increase insulin synthesis and release
• In CNS (GLP1 receptor) - food intake affected, Gastric emptying, nausea
GLP1 agonist
16. Side effect
• Nausea
• Anorexia – weight loss
• Pancreatitis
• Only injectables –SC (except semaglutide-2019)
• No risk of hypoglycemia
• Liraglutide: black box warning- risk of thyroid carcinoma
• Exenatide: avoid in pancreatitis predisposed patients
GLP1 agonist
17. • Inhibit metabolism of incretins (GLP1, GIP)
• DPP IV enzyme is responsible for metabolism of incretins which increase insulin
release.
• No effect on weight
• Increase risk of heart failure with saxagliptin and Alogliptin
DPP IV inhibitors
Sitagliptin (100mg OD), Vildagliptin (50 mg OD/BD), Saxagliptin (5mg/day), Linagliptin (5mg/day),
Alogliptin (25mg/day)
19. • Approved in 2005
• Act on amylin receptor in hind brain
Inhibit glucagon secretion
Delay gastric emptying
Decrease appetite
• Subcutaneously before meals
• Used in both T1 and T2 DM
• Added to decrease insulin requirement
• Should not be mixed in same syringe - different pH
• Risk of hypoglycemia with insulin
• Pregnancy category C
Amylin mimetics
Pramlintide (T1: 15-0 mcg/day; T2: 60-120 mcg/day)
23. Bromocriptine
(1.6 - 4.8 mg)
• Approved in 2009 for diabetes
• D2 agonist
• Effects on blood glucose and may reflect an action in the CNS
Side effects:
• Nausea, vomiting
• Fatigue, headache
• Dizziness
• Orthostatic hypotension
24. Colesevelam
• Approved for Type 2 diabetes as an adjunct to diet and exercise
Mechanism: not established
Reduce intestinal glucose absorption
Dose: 625-mg tablets are available
3 tablets twice daily before lunch and dinner
OR
6 tablets prior to the patient’s largest meal