1. ORAL
HYPOGLYCEMIC
AGENTS

2. INTRODUCTION
Diabetes
Types – 1, 2, others
Pathogenesis
Diagnostic criteria

3. TREATMENT
 CARE
INSULIN
ORAL HYPOGLYCEMICS

4. ORAL
HYPOGLYCEMICS

5. BIGUANIDES
SECRETAGOGUES
THIAZOLIDINEDIONES
ACARBOSE
OTHERS

6. BIGUANIDES
Phenformin, Metformin
No hypoglycemia
Improve lipid profile
Weight loss

7. Dose- 500 mg once to
max 1000 mg bid
SMBG, 2-3 weeks (slow
action, gi side effects)
Monotherapy effective
Or combine with others

8. Mechanism of action
Hepatic gluconeogenesis
decreased
Insulin mediated glucose
disposal
Retard intestinal absorption
Interfere with mitochondrial
respiratory chain

9. Adverse effects
Nausea, pain abdomen, metallic
taste, diarrhoea, anorexia
B12 deficiency
Lactic acidosis
Careful in alcoholics, renal
failure, hepatic disease,
hypotensive states,
radiographic contrasts, if nil
orally

10. SECRETAGOGUES

11. Sulfonylureas - Mechanism
SUR 1 RECEPTORS
Decrease conductance of
ATP sensitive K+ channels
Depolarization of beta
cells
Decrease glucagon
release

12. 1 st generation
Chlorpropamide,
Tolbutamide, Tolazamide
Longer half-life
More hypoglycemia
More side effects

13. 2 nd generation
 Type 2 DM of recent onset
 Reduce both fasting and PP glucose
 Start at low doses – increase after
1-2 weeks interval
 Just before a meal – increase insulin
acutely
(With chronic therapy – more
sustained release)

14. 2nd generation

15. Adverse effects
Hypoglycemia – may recur
Weight gain
Avoid in renal/liver disease
Tolbutamide- reduces iodine
uptake
Chlorpropamide- cholestatic
jaundice, hyponatremia

16. Drug Interactions - positive
Protein binding –
salicylates, sulfonamides
Decrease metabolism –
warfarin, acute alcohol
Synergise –
salicylates, lithium, theoph
ylline

17. Drug Interactions - negative
Inducers –
Phenobarbitone, Phenytoin,
Chronic alcohol, rifampicin
Opposers –
steroids, thiazides, OCPs

18. Same channel in
myocardium
All except glyburide have
a low affinity for this
NO INCREASED
CARDIAC MORTALITY

19. Non-sulfonylureas
Meglitinide – Repaglinide
D-phenylalanine
analogue – Nateglinide

20. Rapid onset, short-lasting
insulin release
Before every meal
Omit if skip meal
Low risk of hypoglycemia
Side effects – Mild headache,
dyspepsia, weight gain, avoid in
liver/renal disease, arthralgia

21. THIAZOLIDINEDIONES

22. PPAR-gamma receptors
(adipocytes)
Insulin SENSITISERS
Lower insulin resistance &
requirement
Redistribute fat from central
to peripheral
Ovulation in PCOS

23. Used as supplements with
others in type 2
Sometimes monotherapy in mild
with diet, exercise
“Decreased mortality due to
MI/Stroke”
NON-RESPONDERS – With
low baseline insulin

24. DOSE
Rosiglitazone – 2-8 mg/day
once or in 2 divided doses
Pioglitazone – 15-45
mg/day once daily

25. ADVERSE EFFECTS

26. Troglitazone – Liver failure
(monitor LFT)
Effect on lipid profile
Peripheral edema, CHF,weight
gain, ANEMIA, Fractures,
macular edema
Rosiglitazone – CARDIAC

27. Pioglitazone – failure of OCP
therapy
Ketoconazole inhibits metabolism
of pioglitazone
Less interactions with
rosiglitazone

28. ALPHA-
GLUCOSIDASE
INHIBITORS

29. ACARBOSE
“REVERSIBLE” inhibition
Decrease post-prandial
hyperglycemia
ANTI-HYPERGLYCEMIC (NOT
HYPOGLYCEMIC)
Weight, TG levels decrease with
chronic therapy (HbA1c less)
Stop-NIDDM trial – in pre-
diabetics, REDUCED DM
2, HTN, CARDIOVASCULAR

30. Role as adjuvant in obese
diabetics
Start at 25 mg evening
50-100 mg with each meal
max dose
Miglitol – more potent in
inhibiting sucrase

31. Adverse effects
FLATULENCE
ABDOMINAL DISCOMFORT
LOOSE STOOLS
( DUE TO FERMENTATION
OF UNABSORBED
CARBOHYDRATES)

32. NOTE:
Gradual upward dose
titration
Avoid in IBD, gastroparesis
If hypoglycemia from
other treatments occurs
while taking these
agents, use glucose

33. RECENT
ADVANCES

34. BROMOCRIPTINE
Improves glycemic
control in obese DM2
Reduces both fasting
and PP glucose levels

35. INCRETIN
EFFECT

36. GLP-1, GIP
DPP 4

37. DPP 4 inhibitors
SITAGLIPTAN
VILDAGLIPTAN
Saxagliptan
Ritagliptan
Alogliptan

38. AMYLIN EFFECT

39. COLESEVELAM
“Bile acid sequestrant”
Mechanism not known
Adverse effects –
Constipation, dyspepsia, int
estinal
obstruction, nausea, pain
abdomen

40. RENAL GLUCOSE
TRANSPORTER
INHIBITORS
Phlorozin
Dapagliflozin
Sergliflozin
Remogliflozin

41. RESVERATROL
Natural compound found in
grape skin
Food sensors activated in
shortage of food like IGF &
TOR
Mimic effect of dietary
restriction
Increase longeivity

42. SALSALATE
Wall Street Journal Health Blog
research on using Salsalate to
prevent or treat type II
diabetes:
Fasting glucose levels of those
who took salsalate declined 13%
compared with those who took
a placebo

43. GLUCOKINASE
ACTIVATORS
PIRAGLIATIN
Hypoglycemia, fatty liver &
hyperlipidemia

44. THANK YOU