Insulin was discovered in 1922 by Banting and Best. The first recipient was Leonard Thompson in 1922. Insulin preparations have evolved from animal insulins in the 1920s to recombinant human insulin in 1977 to long-acting analogues like glargine and detemir. Insulin is synthesized in the pancreas as proinsulin and cleaved into insulin and C-peptide. Insulin regulates blood glucose by stimulating glucose uptake and inhibiting gluconeogenesis and lipolysis. It is indicated for treatment of type 1 diabetes and can be used for type 2 diabetes when other options are inadequate or in special circumstances like surgery. New long-acting analogues allow once-daily dosing with lower risks of hypoglycemia and

1. INSULIN AND INSULIN ANALOGUES

2. History
 Insulin was discovered in 1922 by Frederick G Banting
and his student Charles H Best, for which they were
awarded Nobel Prize
 First recipient of insulin was Leonard Thompson on 23rd
of January 1922
 The molecule was purified for clinical use by Mcleod

3. Some more dates
 1922: discovery of insulin
 1923: discovery and manufacture of animal insulin
preparations
 1946: discovery of Hagedorn protamine insulin (NPH)
 1950s: ultralente, semilente and lente (zinc insulin
suspension)
 1977: discovery of recombinant human insulin
 1980: formulation of biphasic insulin
 1990: discovery of fast acting insulin analogue
 2000s: discovery of glargine insulin analogue
 2004: discovery of detemir insulin analogue
 2013: discovery of insulin degludec analogue

4. Structure
Preproinsulin(110
aa)
• Synthesized in β
cells of pancreas
• Single chain
polypeptide
Proinsulin
• Produced by
removal of 24 aa
Insulin
• Produced by
removal of ‘C’
peptide(35 aa)
• Both ‘C’ peptide and
insulin are realeased
in blood

5. Regulation of insulin

6. Secretion
 Glucose levels more than 70 mg/dl, stimulate insulin
secretion
 Secretion is pulsatile with small secretory bursts
occurring about every 10 min superimposed upon
greater amplitude oscillations of about 80-150 min
 50% insulin is secreted in by the pancreas as basal
insulin and rest is secreted in pulses in response to
meals
 Basal insulin secretion rate is 0.5 U/hr to 1 U/hr

7. Action
 Increases glucose uptake leading to
 Glycogen synthesis
 Utilization
 Storage as fat
 Inhibits
 Glycogenolysis
 Gluconeogenesis
 Proteolysis
 lipolysis

8. Advantages Disadvantages
 Nearly universal response
 Theoretically unlimited
efficacy
 Decreases microvascular
risk
 Better HbA1C reduction as
monotherapy
 Early insulin therapy
improves beta cell function
and glycemic control
 HYPOGLYCEMIA
 Weight gain
 ? Mitogenic effects
 Injectable
 Patient reluctance
 Training requirement

9. Insulin preparations

10. Pre mixed insulins

11. Prandial insulins
Regular insulin Rapidly acting insulin
 Delayed onset of absorption –
to be taken 30 mins before
meals
 Late peak (3 hrs) after
administration – brief period of
hyperglycemia
 Potential hypoglycemic period
3-4 hrs after meal
HYPOGLYCEMIA
 Ultra fast acting – can be taken
5-15 mins before meals or
immediately after
 Peak coincides better with the
rising plasma glucose after
meals
 Action wanes off as glucose
levels decreases
HYPOGLYCEMIA

12. NPH
 Intermediate acting
 Multiple daily dosing required
 Pronounced peak effect - HYPOGLYCEMIA
 Substantial within-patient variability – episodes of
hyperglycemia and HYPOGLYCEMIA

13. Glargine
 Longer duration
 Once daily dosing
 Peakless insulin
 Less chances of hypoglycemia
 Control of fasting blood glucose better
 Provides rest to beta cells

14. Detemir
 Variable duration (12-24 hrs) – dose dependent
duration
 Once or twice dosing
 Peakless insulin
 Minimal intra- and interpatient variability
 Less weight gain
 Lower chances of hypoglycemia as compared to
glargine

15. Degludec
 Ultra long acting ( 40 hours), it has been seen some
insulin activity is is present even at 96 hrs after
injection
 Once daily dosing
 Peakless
 Timeless – flexible timing
 Lower chances of hypoglycemia
 No inter or intrasubject variabilty

17. Comparison
Feature NPH Glargine Detemir Degludec
Duration (hrs) 14-24 24 12-24 40
Dosing Twice Once Once/twice once
Peak (hrs)
6-12 None 3-9 None
Weight gain + +/- +/- +/-
Hypoglycemia + +/- +/- -
Intra- &
interpatient
variability
++ + +/- -

18. Premixed insulin
 Twice daily dosing
 Provide rapid and intermediate acting in one
injection
 Can be used fro initiation of insulin therapy
 Dosage of short acting and intermediate acting
insulin can not be varied to meet the individual
needs of the patient

19. Indications for insulin therapy
 Insulin is the mainstay and only treatment for T1DM
 Treatment of choice in gestational diabetes
 Severe glycemia (>300 mg/dl) in T2DM
 T2DM treatment who develop loss of weight or
ketosis
 Severe sepsis, major surgical procedure, other
intercurrent illnesses
 Add on therapy with oral hypoglycemic drugs in
T2DM

22. Thank you