The document discusses the classification, treatment, and glucose lowering therapies for different types of diabetes. It provides details about the mechanisms of action, examples, A1C reduction, advantages, disadvantages, contraindications, and dosages of various antidiabetic drugs. Insulin is indicated for gestational diabetes, type 1 diabetes, and chronic kidney disease. Metformin, amylin agonists, and GLP1 agonists cause weight loss while sulfonylureas, pioglitazone, and insulin cause weight gain. Pioglitazone reduces fatty liver but increases risk of fractures and heart failure.

1. BY
Dr.V.Padma,
Associate professor of Medicine,
Shree Balaji Medical College,Chrompet,Chennai.

2. OBJECTIVES
At the end of the class the student should be able to
identify which antidiabetic drug is indicated in
different type of diabetes.
Common side effects of antidiabetic drugs.

3. CLASSIFICATION
Type 1 DM
Type 2 DM
Other specific types of diabetes
 Genetic defects
 Exocrine pancreatic diseases
 Endocrinopathies
 Drug or chemical induced,Infections.
Gestational diabetes mellitus

4. TREATMENT
Type 1 DM Insulin→
GDM Insulin→
Type 2 DM -Diet
 -Exercise
 -Medication -Oral hypoglycemic
drugs,Insulin.


5. GLUCOSE LOWERING THERAPIES FOR
TYPE 2 DIABETES
ORAL:
 -BIGUANIDES
 -ALPHA GLUCOSIDASE INHIBITORS
 -DIPEPTIDYL PEPTIDASE 4 INHIBITORS
 -INSULIN SECRETAGOGUES- Sulphonylureas,non
sulphonylureas
 -THIZOLIDINE DIONES
PARENTERAL-INSULIN,GLP-1 agonists, Amylin agonists.
MEDICAL NUTRITIONAL THERAPY

6. MEDICAL NUTRITION THERAPY AND PHYSICAL ACTIVITY
Mechanism of action Decreased insulin resistance,increased insulin secretion
EXAMPLE Low calorie,low fat diet,exercise
A1C Reduction 1-2%
Specific advantages Other health benefits
Specific
disadvantages
Compliance difficult,long term success low
Contra indications
DOSAGE

7. BIGUANIDES
MECHANISM OF
ACTION
Decreased hepatic glucose production,weight loss,improves
peripheral glucose utilization,insulin resistance
EXAMPLE Metformin
A1C Reduction 1-2%
Specific advantages Weight loss
Specific
disadvantages
Lactic acidosis,nausea,diarrhoea.
Contra indications Sr. creatinine>1.5mg/dl,CHF,radiographic contrast
studies,seriously ill patients,acidosis.
DOSAGE 500-1000MG BID

8. ALPHA GLUCOSIDASE INHIBITORS
Mechanism of action Decreased glucose absorption-by inhibiting the enzyme that
cleaves oligosaccharides into simple sugars in intestinal lumen.
EXAMPLE Acarbose,miglitol,voglibose
A1C Reduction 0.5-0.8%
Specific advantages Reduces post prandial glycemia.
Specific
disadvantages
GI flatulence,diarrhoea,abdominal distension-increased
delivery of oligosaccharides to large bowel
Contra indications Renal or liver disease,pt with inflamatory bowel
disease,gastroparesis,cr>2 mg%,avoid cotreatment with
antacids,bile acid resins.
DOSAGE Acarbose,Miglitol-25-50mg,Voglibose-0.2-0.3mg.

9. THIAZOLIDINEDIONES
Mechanism of action Increased glucose utilization,decreased insulin resistance
Binds to PPAR G nuclear receptor,-promote adiposite
differentiation,reduces hepatic fat,reduces insulin resistance-
increases FA storage and increases adiponectin levels,induces
ovulation in premenopausal with PCOS.
EXAMPLE pioglitazone
A1C Reduction 0.5-1.4%
Specific advantages Lower insulin requirements
Specific
disadvantages
Weight gain,peripheral edema,CHF,fractures,macular
edema,rosi increases risk of MI.
Contra indications CHF,liver failure
DOSAGE PIO-15-45MG,

10. DIPEPTIDYL PEPTIDASE 4 INHIBITORS
Mechanism of action Prolongs endogenous GLP-1 action
EXAMPLE Sitagliptin,vildagliptin
A1C Reduction 0.5-1%
Specific advantages No hypoglycemia
Specific
disadvantages
Contra indications Reduce dose with renal disease
DOSAGE 100 mg daily

11. SULFONYLUREAS
Mechanism of action Increases insulin secretion by interacting with ATP- sensitive
potassium channel on the beta cell
EXAMPLE Glimepride,gliclazide,glibenclamide
A1C Reduction 1-2 %
Specific advantages Lower fasting blood glucose
Specific
disadvantages
Hypoglycemia,weight gain
Contra indications Renal/liver disease
DOSAGE Glibenclamide,glipizide-2.5-10mg,glimepride-1-
4mg,gliclazide-40-120mg

12. NON SULFONYL UREAS
Mechanism of action Increases insulin secretion by interacting with ATP-sensitive K
channel
EXAMPLE Repaglinide,nateglinide
A1C Reduction 1-2%
Specific advantages Short onset of action,lowers PP glucose
Specific
disadvantages
hypoglycemia
Contra indications Renal/liver disease
DOSAGE Repa-0.5-16mg,nate-180-360mg

13. GLP-1 AGONISTS
Mechanism of action Increase insulin,decreased glucagon,slow gastric emptying
EXAMPLE exenatide
A1C Reduction 0.5-1mg%
Specific advantages Weight loss
Specific
disadvantages
Injection,nausea,increased risk of hypoglycemia with
secretogogues
Contra indications Renal disease,agents that slow GI motility
DOSAGE 5microgm sc bid-10 microgm bid

14. AMYLIN AGONIST
Mechanism of action Slow gastric emptying,decreased glucagon,does not alter
insulin level
EXAMPLE pramlintide
A1C Reduction 0.25-0.5%
Specific advantages Reduced postprandial glycemia,weight loss
Specific
disadvantages
Injection,nausea,increased hypoglycemia with insulin
Contra indications Agents that slow GI motility
DOSAGE 15microgm sc before each meal-upto60 in type 1-120 micro
gm in type 2 DM .

15. INSULIN
Mechanism of action Increased glucose utilization and other anabolic actions
EXAMPLE Regular,NPH,analogues
A1C Reduction No limit
Specific advantages Known safety profile
Specific
disadvantages
Injection,weight gain, hypoglycemia
Contra indications nil
DOSAGE According to requirement

16. PATIENT WITH TYPE 2 DIABETES
MNT,INCREASED PHYSICAL ACTIVITY,METFORMIN
REASSESS A1C
COMBINATION THERAPY,
METFORMIN+OTHER AGENTS
REASSESS A1C
COMBINATION THERAPY
METFORMIN+2 OTHER AGENTS REASSESS A1C
INSULIN+MET

17. SUMMARY
Insulin is indicated in gestational diabetes,Type 1
DM,Chronic kidney disease,medical or surgical
emergencies.
Post prandial hyperglycemia is treated by
acarbose,non sulphonylureas and amylin
agonists,short acting insulins.
Serious complication of metformin is lactic acidosis.
Fasting hyperglycemia is treated by biguanides and
sulphonylureas.

18. SUMMARY
Metformin,amylin agonists, GLP1 agonsts cause
weight loss.
Sulphonylureas,pioglitazone and insulin causes
weight gain.
Pioglitazone causes fat redistribution and thus
reduces fatty liver,but causes weight gain,increased
risk of fractures and aggravates cardiac failure.
Metformin and pioglitazone reduces insulin
resistance.

19. 1 MCQ
Which antidiabetic causes weight loss
1)metformin
2)glibenclamide
3)pioglitazone
4)insulin

20. 2 MCQ
Antidiabetic drug which induces ovulation in
polycystic ovarian disease
1)sulphonyl ureas
2)insulin
3)metformin
4)acarbose

21. 3 MCQ
Drug of choice in gestational diabetes mellitus is
1)pioglitazone
2)insulin
3)amylin agonists
4)glimepride

22. 4 MCQ
Which drug reduces postprandial hyperglycemia
1)glimepride
2)metformin
3)acarbose
4)pioglitazone

23. 5 MCQ
Which antidiabetic drug is safe in chronic kidney
disease
1)metformin
2)gibenclamide
3)pioglitazone
4)insulin

29. PHARMACOKINETICS
PREPARATION ONSET
hrs
PEAK,
hrs
DURATION
hrs
75/25-75%protamine
lispro,25%lispro
70/30-70%protamine
aspart,30%aspart
50/50-50%protamine
lispro,50%lispro
70/30-
70%NPH,30%regular
insulin
50/50-50%NPH,50%reg
<0.25
<0.25
<0.25
0.5-1
0.5-1
1.5
1.5
1.5
Dual
dual
10-16
10-16
10-16
10-16
10-16

31. Myristic
acid
LysDetemir
ArgThrLysProGlyGlargine
ThrGluProLysAsnGlulisin
e
ThrProLysAsnLispro
ThrLysAspartic
acid
AsnAspart
ThrLysProAsnAsnHuman
B31
And
B32
B30B29B28B3A21Source/
Type
B- chain PositionA-
chai
n
Position
Amino Acid Substitutons
Myristic
acid
LysDetemir
ArgThrLysProGlyGlargine
ThrGluProLysAsnGlulisin
e
ThrProLysAsnLispro
ThrLysAspartic
acid
AsnAspart
ThrLysProAsnAsnHuman
B31
And
B32
B30B29B28B3A21Source/
Type
B- chain PositionA-
chai
n
Position
Amino Acid Substitutons

32. GUIDELINES-CARE OF DM
Self monitoring of blood glucose
A1C testing-2-4 times/year
Diabetic education-annual
MNT and education-annual
Eye examination-annual
Foot examination-1-2 times/year by physician,daily by
patient
DM nephropathy screening-annual
BP measurement-quarterly
Lipid profile,sr.creatinine-annual
Influenza,pneumococcal vaccinations
Antiplatelet therapy

33. PREPARATION ONSET,Hrs PEAK,Hrs Duration,hr
SHORT ACTING,SC
LISPRO,GLULISINE
ASPART
REGULAR
<0.25
0.5-1.0
0.5-1.5
2-3
3-4
4-6
SHORT ACTING,
INHALED regular
<0.25 0.5-1.5 4-6
LONG ACTING
NPH
DETEMER
GLARGINE
1-4
1-4
1-4
6-10
MIN 6-14H
MIN PEAK
10-16
12-20
24
PHARMACOKINETICS