BENCLAMET

(Metformin)
 BENCLAMET
(Metformin)
• Belongs to the class of drugs called
Biguanides

• Oral antihyperglycemic agent

Mechanism of action
Decreases gluconeogenesis

Less Glucose output from liver

Decreases glucose in blood

Glucar to some extent can also -
● Improves insulin sensitivity in peripheral
tissues.

● Decrease intestinal absorption of glucose.

 Pharmacokinetics
– Food decreases and delays absorption

– Bioavailabilty is 50 - 80% under fasting

conditions.
– Excreted unchanged in urine.

– Plasma half-life is 6.2 hours.

 Pharmacodynamics
Effect On Blood Glucose
• Significantly decreases hepatic
glucose production.
• Decreases fasting and postprandial
plasma glucose, but mainly FPG.
 Pharmacodynamics
Cardioprotective effects

Variables Effects
Bodyweight Decrease
BPNo effect
Triglycerides Decrease to neutral
Total Cholesterol Decrease to neutral
LDL Decrease to variable
HDL Increase to variable
Lipoprotein(a) Decrease
Hypercoagulability Decrease
C-Reactive Protein Decrease to variable
Endothelial function Improve
Cardiovascular Events Decrease
 Indication
• Drug of first choice in obese with type-2
diabetes mellitus.
• USFDA approved in children > 10 years
of age with type-2 DM.
• Metabolic Syndrome.

• IGT and to prevent diabetes in patients

with IGT.
 Dosage
• Dose of BENCLAMET has to be individualized

• The recommended starting dose of BENCLAMET is

500 mg b.i.d or 850 mg once a day with meals.

• The maximum dose is 2550 mg per day.

• BENCLAMET can be combined with insulin,

sulfonylureas or glitazones if there is no response with
monotherapy.
 Adverse Effects
• Diarrhea, nausea, vomiting,
abdominal bloating, flatulence,
anorexia, which decreases with
continuous use.

• Unpleasant metallic taste, which

resolves spontaneously
 Drug Interactions

There is no significant drug

interactions with BENCLAMET
 Contraindications
• Hypersensitivity.

• Acute or chronic acidosis.

• Renal disease.

• Congestive heart failure.

 Precautions & Warnings
• Incidence of lactic acidosis is very low with This is
particularly in patients with renal disease.

• Alcohol may potentiate effects of metformin on lactate

metabolism.

• Hypoglycemia may occur when used as a combination

therapy.
GLIMETOP
Glimepiride
 GLIMETOP
GLIMETOP is an oral hypoglycemic and
belongs to class of drugs known as
Sulfonylurea.

GLIMETOP is a second generation

sulfonylurea.
 Mode of Action
• Binds with sulfonylurea receptors (SUR) and causes
closure of ATP sensitive K+ channels.

• This leads to depolarization of cell membrane.

• Voltage dependent Ca++ channels open up.

• Influx of extracellular Ca++ triggers release of insulin.

GLIMETOP can stimulate the release

of insulin from functional beta cells
 Mode of action
• Some extrapancreatic effect also, that is
GLIMETOP also increases peripheral
insulin sensitivity to some extent.

• Major effect is due to stimulation of beta

cells
 Pharmacokinetics
• Some active metabolites are present.
• Excreted in feces.
• Elimination half-life is 5 hours, can increase to
9 hours after multiple doses.
• No significant differences in pharmacokinetics
of elderly.
 Pharmacodynamics
• Significantly improves both first and second
phase of insulin secretion.

• Stimulates insulin production primarily after meals

when glucose concentrations are highest, but
controls glucose throughout the day.

• Causes significant decrease in serum HbA1c level.

 Pharmacodynamics
• Maintains myocardial preconditioning.

• Causes significantly less hypoglycemia

compared to glibenclamide.

• Safe in renal failure patients; no dosage

adjustment is required.
 Indications
• Treatment of type-2 diabetes mellitus as an
adjunct to diet and exercise

• First drug of choice in lean type-2 diabetic

patients

• Combination therapy with metformin,

thiazolidinediones and insulin.
 Dosage
• The recommended starting dose is 1-2 mg once daily
with breakfast or the first main meal.

• Maximum dose is 8 mg. if patients do not respond to

maximum dose, add metformin.

• Attempts should be made to identify the effective

dose of each drug.
 Adverse effects
• Hypoglycemia

• Vomiting, gastrointestinal pain & diarrhea

• Rare skin reactions like pruritus, erythema, urticaria

• Agranulocytosis, thrombocytopenia, etc

 Contraindications
• Hypersensitivity.

Warnings &
Precautions
• Hypoglycemia may occur.
• Loss of control of blood glucose is seen when patient
is exposed to stress, infection or surgery.
• Should not be used in pregnancy, nursing mothers
and children.
 Drug Interactions
• Hypoglycemic action is potentiated with
NSAID’s, salicylates, sulfonamides,
chloramphenicol, & beta blockers.

• Drugs are thiazides, diuretics, corticosteroids,

phenothiazines, thyroid products, estrogens,
oral contraceptives, nicotinic acid may cause
hyperglycemia
Advantage over Glibenclamide
• Lower risk of hypoglycemia (due to quicker
dissociation from receptors).
• Faster onset of action (due to quicker binding to
receptors).
• Better protection during ischemia and better
myocardial preconditioning, hence better
cardioprotective effect.
• Less beta cell fatigue (due to quicker dissociation
from receptors, hence less stimulation).
 Advantage over
Glipizide
The efficacy of Glimepiride is similar
to that of glipizide, however,
glimepiride produced a more rapid
lowering of fasting plasma glucose
levels than glipizide.
 Advantage over
Gliclazide
In clinical trials efficacy were similar.
However Glimepiride has a genuine once a
day dose compared to gliclazide which has to
be given preferably bid.
 Overall Advantage of
Glimepiride
• Glimepiride is recommended as once a day therapy.
Whereas all other sulfonylureas are recommended as
bid at higher dosage.

• Glimepiride do not, at least in theory, stimulate insulin

secretion in the presence of normoglycemia or when
there is no food intake.

• Glimepiride is the only sulfonylurea which is USFDA

approved to be used with insulin.

• Glimepiride appears to possess a greater insulin-

sparing property than other sulfonylureas.
GLYTOP-SR
 GLYTOP-SR

COMPOSITION
Each tablet contains :
Glipizide 5 mg/10 mg in a SR form

INDICATION
• Type 2 Diabetes Mellitus
 GLYTOP-SR

RATIONALE
• Longer acting agents like glibenclamide are
efficacious but have
1) Higher rates of hypoglycemia

• Shorter acting agents like immediate release

glipizide are efficacious and have low risk of
hypoglycemia but have 2 disadvantages :
(i) Dosing more than OD
(ii) Greater excursions in plasma drug levels
Ref : Simonson D, diabetes Care 1997; 20(4): 597-606.
 What is the mechanism of
action of Glytop-SR?
• Like other SUs, stimulate insulin release
from pancreatic beta cells by blocking
potassium channels.
• Unlike other SUs, binds almost to
pancreatic K+ channels (140kDA & 65kDa
protein)
 GLYTOP-SR

PHARMACOKINETICS
• Tmax : 6-12 h
• Steady state : 5th day
6-7 days in elderly
• Effect of food : None
• Metabolism : Liver (90%)
• Excretion : Urine and feces
 GLYTOP-SR
DOSAGE
Initial
No fixed dosage regimen
Recommended starting dose : 5mg OD with breakfast
Maximum : 20mg OD
Switch from conventional Glipizide
Nearest equivalent dose
Switch from other SUs
Start with 5mg OD
Type 2 DM Patients on Insulin
<20 units - discontinue insulin, start with 5mg OD Glytop-SR
>20 units -Reduce insulin dosage by 50% and start 5mgOD Glytop-
SR.
 GLYTOP-SR

COMPETITION
vs. Conventional Glipizide

1. Superior in lowering FBG

2. Less peak to trough fluctuations
3. Incidence of hypoglycemia
comparable
 GLYTOP-SR

COMPETITION

vs. Glibenclamide

1. Lesser risk of hypoglycemia

2. Equieffective
3. Lower C-peptide concentrations
 GLYTOP-SR
USPs
• Most frequently used sulfonylurea in US
(Skyler JS, Medical Clinics of N. America
1998)
• Potent and rapid acting - PPBG control
• 24 hour effect - Nocturnal and FBG control
• Better than IR Glipizide with respect to :
- FBS control
- Plasma insulin
• No effect on lipid profile, body weight and
exercise induced hypoglycemia