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THERAPIES
IN
DIABETES MELLITUS
(TYPE II)
BY
SWAPNAJEET SAHOO
4th yr
VSS MEDICAL COLLEGE,BURLA
INTRODUCTION
Diabetes mellitus is a syndrome characterized by hyperglycemia
due to
It has been estimated that over 230 million diabetics by 2010 &
3.0
-50%
β -Cell volume (%)
2.5
2.0 -63%
1.5
1.0
0.5
0.0
ND IFG T2DM ND T2DM
Obese Lean
ND=non-diabetic; IFG=impaired fasting glucose; T2DM=Type 2 diabetes mellitus
Butler et al. Diabetes. 2003
Excessive hepatic
glucose production in
Type 2 diabetes
Insulin; IR
Hepatic
glucose Glucagon
output Fasting &
postprandial
hyperglycaemia
Plasma glucose
concentration
IR=insulin resistance
PRESENT ORAL
HYPOGLYCEMIC DRUGS
SULFONYL UREAS:
1ST GENERATION- Tolbutamide
BIGUANIDES – Metformin
MEGLITINIDE ANALOGS – Repaglinide,
Nateglinide
THIAZOLIDINEDIONES –
ORAL HYPOGLYCEMIC
DRUGS
ADVERSE EFFECTS OF
Sulfonyl ureas
OHAS
- Hypoglycemia
(most common)
Metformin – lactic acidosis & GI
disturbances
Meglitinide analogues – Hypoglycemia(
less) & wt. gain
Thiazolidinediones- plasma volume
expansion
- edema & heart failure
- weight gain
- mild anemia
Alfa glucosidase inhibitors – flatulence
Incretin
Therapies
WHAT R
INCRETINS ?
Incretins are gut peptides that potentiate insulin secretion
Incretins are gut peptides that potentiate insulin secretion
during eating.
mainly 2 types – GIP ( gastro inhibitory peptide)
- GLP-1 ( glucagon like peptide )
GIP- secreted from K cells of intestine (Duodenum)
doesnot delay gastric emptying
doesnot affect pancreatic alpha cells secretion of
glucagon.
GLP-1 – secreted from L cells of intestine ( ileum & colon)
stimulates glucose dependent insulin release
delays gastric emptying.
So, GLP-1 has been considered a viable therapeutic
approach in management of T2DM.
Incretin effect on insulin secretion
Control subjects (n=8) People with Type 2 diabetes (n=14)
80 80
60 60
Insulin (mU/l)
Insulin (mU/l)
40
Incretin 40
effect
20 20
0 0
0 60 120 180 0 60 120 180
Time (min) Time (min)
• Leads to a reduction of
GLP-1 is secreted from food intake
L-cells of the jejunum
and ileum • Improves insulin sensitivity
Long-term effects
That in turn… in animal models:
• Increase of β-cell mass
and improved β-cell function
Drucker. Curr Pharm Des. 2001
Drucker. Mol Endocrinol. 2003
GLP-1 enhancement
GLP-1 secretion is impaired in Type 2 diabetes
Natural GLP-1 has extremely short half-life
EXENATIDE LAR
Microsphere suspension of exenatide.
Once a weekly regimen in a dose of 0.8-2.0 mg
Significant decrease in HbA1c – 1.4-1.7% has been seen
Offers potential of 24 hrs glycemic control & wt.
reduction when combined with metformin &/or diet &
exercise in T2DM
Long term trials are underway
Diagram of how DPP-4
inhibition might be expected
to improve blood glucose
control
Increase
Increaseinsulin secretion
insulin secretion
Active GLP-1
Active GLP-1
Decrease
Decreaseglucagon release
glucagon release
Hypoglycaemia No No
PRAMLINTIDE(Symlin)
Amylin analog ,differs from it by 3 AAs
Slows gastric emptying & suppresses post prandial
glucagon secretion
Given SC prior major meals.
Indicated in T2DM – adjunct T/t to meal time insulin
with/without a
SU/metformin.
Advantages - wt. loss of 1 – 1.5 kg over 6 months
- decreases HbA1c by 0.5 – 0.7%
A/E – nausea(50% cases), headache ,hypoglycemia (rare)
WHO MIGHT BE BENEFITED
THE MOST ?
www.diabeteshealth.com
www.dentocafe.com
BOOKS:
JOSLIN’S DIABETES MELLITUS
KATZUNG PHARMACOLOGY
LIPPINCOTT
PHARMACOLOGY