IBFORMIN

WHAT IS THE ROLE OF

GLUCOSE IN THE BODY?
 Glucose acts as a FUEL for the body….

 Fuel for the BRAIN:

• The brain normally relies almost exclusively on glucose to fuel
its energy needs.

• Because of its high energy demands and inability to store

glucose, the brain requires a constant supply of the sugar
WHAT IS THE ROLE OF
GLUCOSE IN THE BODY?
Fuel for Skeletal Muscles:
• The skeletal muscles utilize large amounts of glucose during
exercise.

• Muscle tissue also normally absorbs large amounts of glucose

from the bloodstream during exercise

Fuel for other Tissues & Organs:

• Human body also utilizes glucose to manufacture other
important structural molecules.

• For example, the glycoprotein collagen ( found in skin,

muscles, bones and other body tissues) consists of a protein
backbone plus simple sugars, including glucose

Ref: http://www.livestrong.com/article/133891-the-importance-
HOW GLUCOSE IS
REGULATED IN BODY?
 PANCREAS PLAY AN
IMPORTANT ROLE
Pancreas has 2 different types of cells which helps in glucose regulation.
ACTIONS OF ALPHA & BETA CELLS

 Pancreas and its hormone control the blood glucose in the

body.

Type of Cell Hormone Action

Beta-cell Insulin Blood Glucose

Alpha Cell Glucagon Blood Glucose

HORMONAL REGULATION OF GLUCOSE
WHAT IS INSULIN?
 Insulin is the hormone
responsible for reduction
in blood glucose level.

 It is produced in beta
cells of pancreas.

 It carries the glucose

molecule to the cells.
HOW INSULIN HELPS
CONTROL BLOOD GLUCOSE
LEVELS?
 Insulin is normally secreted by the beta cells (a type of islet
cell) of the pancreas.

 There is always a low level of insulin secreted by the

pancreas

 Amount of Insulin secretion go up with more glucose

enters in blood and go down with less amount remains in
blood.

 In response to insulin, these cells absorb glucose out of

the blood, having the net effect of lowering the high blood
glucose levels into the normal range.
HOW INSULIN HELPS
CONTROL BLOOD GLUCOSE
LEVELS?
 DIABETES
Chronic metabolic disorder characterized
by
persistent hyperglycaemia
due to
insulin deficiency and / or insulin resistance
DIAGNOSIS O DIABETES:
ADA CRITERIA

ADA. 2. Classification and Diagnosis. Diabetes Care 2016;38(suppl 1):S9; Table 2.1
WHAT IS HBA1C: A
GLYCOSYLATED HB
 Form of hemoglobin that is
measured primarily to
identify the average plasma
glucose concentration over
prolonged periods

 Serves as a marker for

average blood glucose
levels over the previous 3
months before the
measurement as this is the
lifespan of red blood cells.
TYPES OF DIABETES
 Majorly 3 types of
Diabetes exists
a) Type 1 Diabetes
b) Type 2 Diabetes
c) Gestational Diabetes
SYMPTOMS OF
DIABETES
DIABETIC COMPLICATIONS
 TYPE 1 DIABETES: WHAT IS IT?
Type 1 diabetes occurs because the
insulin-producing cells (called beta
cells) of the pancreas are damaged.

Produce little or no insulin, so

sugar cannot get into the body's
cells for use as energy.

This causes blood sugar levels to

rise.
CAUSES OF IDDM
Type 1 diabetes is caused by a combination of genetic (88%) and
non-genetic (or environmental – such as virus exposure 12%) risk
factors.
 TYPE 2 DIABETES:
WHTAT IS IT?
People with Type 2 diabetes produce
insulin. However, there is either not
enough insulin or it doesn't work
properly in the body.

insulin is not used as it should be,

sugar cannot get into the body's
cells for use as energy. This causes
blood sugar to rise.
CAUSES AND RISK
FACTORS OF NIDDM
CAUSES AND RISK
FACTORS OF NIDDM
Type 2 Diabetes is caused by a combination of genetic and non-
genetic (or environmental) risk factors.
DIABETES:
TREATMENT GOALS
1. Glucose control
2. Normal lipid levels: LDL-C < 100, TG <150
3. Blood pressure : Systolic < 140 mm Hg &
Diastolic < 80 mm Hg
4. Weight management
5. Physical activity : Start with 10-15 min daily and
progress gradually to 30 min activity daily
6. Cessation of smoking
GLYCEMIC GOAL RECOMMENDATIONS FOR
NON PREGNANT ADULTS WITH DIABETES

 A1C <7.0%*
 Preprandial plasma glucose 80–130 mg/dL* (4.4–
7.2 mmol/L)
 Peak postprandial plasma glucose† <180 mg/dL* (<10.0
mmol/L)

REF: ADA. 6. Glycemic Targets. Diabetes Care 2015;38(suppl 1):S37; Table 6.2
TREATMENT OPTIONS:
DRUG THERAPY
1.Insulin and insulin analogues

2.Insulin secretagogues:
a.sulphonylureas- Glimepiride, Gliclazide
b. Meglitinide - Repaglinide
3.Insulin sensitizers:
a.Biguanide- Metformin
b.Thiazolidinediones- Pioglitazone, Rosiglitazone

4. Alpha glucosidase inhibitors : Acarbose, Voglibose, Miglitol

5. SGLT2 Inhibitors (Gliflozins)

Dapagliflozin, Canagliflozin, Empagliflozin
6. DPP4 Inhibitors (Gliptins): Sitagliptin, Teneligliptin, Lindagliptin
Before moving on to the treatment of Type 2 DM
Let’s Understand

PATHOPHYSIOLOGY
OF TYPE 2 DIABETES
INSULIN CARRIES
GLUCOSE TO THE CELL
BETA CELLS OF PANCREAS
RELEASES INSULIN
INSULIN BINDS WITH IR & ALLOWS GLUCOSE TO GO
INSIDE THE CELL
INSULIN RESISTANCE AND -CELL DYSFUNCTION
ARE CORE DEFECTS OF TYPE 2 DIABETES

Genetic susceptibility,
obesity, Western lifestyle

Insulin -cell
resistance IR  dysfunction

Type 2 diabetes
Rhodes CJ & White MF. Eur J Clin Invest 2002; 32 (Suppl. 3):3–13.
INSULIN RESISTANCE
INSULIN SENSITIVE
 Generally with meal, blood glucose level rise triggering the
pancreas to produce insulin.

 The hormone travels through the body and induces fat and
muscle cells to absorb excess glucose from the blood for use
as energy.

 As the cells take up glucose, blood glucose levels fall and

flatten out to a normal range.
INSULIN RESISTANCE
 People with insulin resistance, also known as impaired insulin
sensitivity, have built up a tolerance to insulin, making the
hormone less effective.

 As a result, more insulin is needed to persuade fat and muscle

cells to take up glucose and the liver to continue to store it.
INSULIN RESISTANCE LEADS
TO LOSS OF BETA CELLS
 Over time, insulin resistance tends to get worse, and the
pancreatic beta cells that make insulin can wear out.

 In response to the body's insulin resistance, the pancreas

deploys greater amounts of the hormone to keep cells
energized and blood glucose levels under control.

 Eventually, the pancreas no longer produces enough

insulin to overcome the cells' resistance.

 The result is higher blood glucose levels (prediabetes) and,

ultimately, type 2 diabetes

Ref: Erika Gebel, PhD. Understanding Insulin Resistance; http://www.diabetesforecast.org/

INSULIN RESISTANCE LEADS
TO LOSS OF BETA CELLS
Insulin Resistance major Risk Factor for
Type 2 Diabetes
WHAT IS METABOLIC
SYNDROME?
 Metabolic syndrome, also called insulin resistance
syndrome, is a group of traits and medical conditions linked to

Overweight and obesity that puts

People at risk for both CVD and type 2 diabetes.

Insulin Resistance Responsible for

Metabolic Syndrome

Ref: https://www.niddk.nih.gov/health-information/diabetes/overview/what-is-diabetes/prediabetes-insulin-
resistance#star
INSULIN RESISTANCE
INCREASE CVD RISK
 People who are obese or who have metabolic syndrome,
insulin resistance, type 2 diabetes, or prediabetes often also
have low-level inflammation throughout the body.

 They also develop blood clotting defects that increase the risk
of developing blood clots in the arteries.

 These conditions contribute to increased risk for CVD.

Insulin Resistance increase risk of CVD.

Ref: https://www.niddk.nih.gov/health-information/diabetes/overview/what-is-diabetes/prediabetes-insulin-
resistance#star
CAN INSULIN RESISTANCE
BE REVERSED?
 By losing weight and being more physically active, people can
reverse insulin resistance and prediabetes, thus preventing or
delaying type 2 diabetes.

 People can decrease their risk by

Eating a healthy diet and reaching and maintaining a healthy

weight
Increasing physical activity
Not smoking
Taking medication

Ref: https://www.niddk.nih.gov/health-information/diabetes/overview/what-is-diabetes/prediabetes-insulin-
resistance#star
METFORMIN FOR INSULIN
RESISTANCE AND TYPE 2
DIABETES
METFORMIN - REVERSE
INSULIN RESISTANCE
 Mechanism of Metformin is not clearly understood.

 Possible mechanism include

Increased insulin receptor tyrosine kinase activity

Enhanced glycogen synthesis (conversion of glucose to
glycogen)
An increase in the recruitment and activity of GLUT4 glucose
transporters ( GLUT4 require for entry of glucose in cell)
In adipose tissue, metformin promotes inhibits lipolysis
(breakdown of lipid and fat), which may indirectly improve
insulin sensitivity through reduced lipotoxicity.
Ref: Giannarelli R.Reducing insulin resistance with metformin: the evidence today. Diabetes Metab.2003 Sep;29(4 Pt
2):6S28-35.
METFORMIN - MECHANISM
OF ACTION
 Metformin’s main action is to decrease the overproduction of glucose by
the liver, a common problem in prediabetes and type 2 diabetes.

 The action of metformin helps lower blood sugar levels particularly during
the night to keep fasting glucose levels under control, but it also helps control
blood glucose throughout the day.

 Metformin also increases the uptake of glucose by your muscles.

 Overall, metformin decreases insulin resistance and improves insulin

sensitivity, thereby helping the insulin your body still makes work more
effectively.
METFORMIN - MECHANISM
OF ACTION
METFORMIN - EFFICACY
 metformin treatment was associated with significant
improvements in fasting plasma glucose (5.3 mmol/L) and
lower HbA1c(2.4%)

 Metformin also shows significantly lower total cholesterol.

Ref: Adam C Robinson et al. The Effects of Metformin on Glycemic Control and Serum Lipids in Insulin-Treated
NIDDM Patients With Suboptimal Metabolic Control. Diabetes Care 1998 May; 21(5): 701-705
METFORMIN – REDUCE CV
RISK AS PER UKPDS STUDY
IBFORMIN SR
Metformin 500 mg Sustained Release
IBFORMIN SR-
COMPOSITON
 IBFORMIN SR is available in 2 dosage forms.

 1)Each tablet of IBFORMIN 500 SRcontains

Metformin Hydrochloride SR ………500 mg

 2) Each tablet of IBFORMIN 1000 SRcontains

Metformin Hydrochloride SR ………1000 mg
IBFORMIN SR -
INTRODUCTION

 Ibformin SR is Extended-Release Tablet which are oral

antihyperglycemic drugs used in the management of type 2
diabetes.

Ref: GLUCOPHAGE. Product Monograph. Bristol-Myers Squibb Company

 IBFORMIN SR -
PHARMACOKINETICS
 Absorption

Cmax – 1.1 hr for 100 mg

Bioavailability – 50-60%

 Distribution

Metformin is negligibly bound to plasma proteins

 Metabolism - Hepatic

 Elimination

90% of the absorbed drug is eliminated via the renal route within the first 24
hours

Hallf-life - 6.2 hours

Ref: GLUCOPHAGE. Product Monograph. Bristol-Myers Squibb Company
IBFORMIN SR -
INDICATIONS

 IBFORMIN SR can be given as first line therapy for the

management of Type 2 Diabetes with newly diagnosed Type 2
Diabetes Mellitus patients along with diet control and exercise.
IBFORMIN SR - DOSAGE
AND ADMINISTRATION
 IBFORMIN SR should generally be given once daily with the
evening meal.

 IBFORMIN SR should be started at a low dose, with gradual

dose escalation

 The maximum recommended daily dose of IBFORMIN SR in

adults is 2000 mg

Ref: GLUCOPHAGE. Product Monograph. Bristol-Myers Squibb Company

 RECOMMENDATIONS
 The American Diabetes Association and the European
Association for the Study of Diabetes consensus algorithm
for the treatment of type 2 diabetes recommends beginning
metformin treatment at diagnosis.

Ref: Bianca Hemmingsen, MD, PhD et al.Sulfonylurea versus metformin monotherapy in patients with type 2 diabetes: a
Cochrane systematic review and meta-analysis of randomized clinical trials and trial sequential analysis; CMAJ Open. 2014
Jul-Sep; 2(3): E162–E175
IBFORMIN SR - SPECIAL
POPULATIONS

 Pregnancy - Pregnancy category B

There are no adequate and well-controlled studies in

pregnant women. Metformin was not teratogenic in rats and
rabbits at doses up to 600 mg/kg/day

 Nursing Mothers

Studies in lactating rats show that metformin is excreted into

milk
Ref: GLUCOPHAGE. Product Monograph. Bristol-Myers Squibb Company
IBFORMIN SR - ADVERSE
REACTIONS
 Commonly reported side effects of metformin include:

Lactic acidosis
Diarrhea
Nausea
 Vomiting,
 Flatulence

Ref: GLUCOPHAGE. Product Monograph. Bristol-Myers Squibb Company

CLINICAL TRIALS
 METFORMIN VS SUFONYL UREAS -
CARDIAC SAFETY
 Researchers reported that diabetes patients who used sulfonylureas had
a higher risk of death from all causes and a higher risk of heart failure
than diabetes patients who used the most widely prescribed diabetes
drug, metformin

 Compared with metformin, single-drug treatment with first- and second-

generation sulfonylureas (eg. Glibeclamide, Gliclazide) was associated
with up to a 61% increased risk for death.

 Users of second-generation sulfonylureas had up to a 30% higher risk for

congestive heart failure.

Ref: http://www.webmd.com/diabetes/news/20091204/metformin-vs-sulfonylureas-for-diabetes#1
 METFORMIN VS SULFONYLUREA –
WEIGHT GAIN
 Sulfonylureas, thiazolidinedione, and insulin are associated with
weight gain,

 Metformin is weight neutral or associated with modest weight loss.

 Since obesity aggravates insulin resistance, beta cell failure, and

cardiovascular risk, treatment of diabetes also should consider
weight gain effects of therapy.

Ref: Vicky Cheng and Sangeeta R. Kashyap. Weight Considerations in Pharmacotherapy for Type 2 Diabetes
J Obes. 2011; 2011: 984245.
 METFORMIN VS SULFONYLUREA –
HYPOGLYCEMIA

 Sulfonylurea resulted in greater weight gain compared with

metformin.

 Significantly more patients of mild hypoglycemia & severe

hypoglycemia reported in the sulfonylurea arm than in the
metformin arm

Ref: Bianca Hemmingsen, MD, PhD et al.Sulfonylurea versus metformin monotherapy in patients with type 2 diabetes: a
Cochrane systematic review and meta-analysis of randomized clinical trials and trial sequential analysis; CMAJ Open. 2014
Jul-Sep; 2(3): E162–E175
ADVANTAGES OF EXTENDED-RELEASE
METFORMIN IN PATIENTS WITH TYPE 2
DIABETES MELLITUS.

 Background:

 Metformin is a first-line pharmacological treatment for patients

with type 2 diabetes mellitus because of its favorable overall
profile, including its glucose-lowering ability, weight-neutral
effects, and low risk of hypoglycemia

 However, gastrointestinal (GI) intolerance may limit use in

some patients.
ADVANTAGES OF EXTENDED-RELEASE
METFORMIN IN PATIENTS WITH TYPE 2
DIABETES MELLITUS.

 Metformin SR Vs Metformin IR (Side Effect Profile):

Maximum plasma metformin concentrations are reached more slowly

with the extended-release formulation compared with conventional
immediate-release metformin, so improves GI tolerability, allows once-
daily dosing

Tolerability is better with SR formulation compared to IR.

 Metformin SR Vs Metformin IR (Efficacy)

Extended-release metformin is as effective as immediate-release

metformin in patients newly started on metformin
ADVANTAGES OF EXTENDED-RELEASE
METFORMIN IN PATIENTS WITH TYPE 2
DIABETES MELLITUS.

 Metformin SR Vs Metformin IR (Patient Compliance)

Metformin extended-release formulation has the potential to
improve patient adherence with a simpler dosing regimen and
increased tolerability.

Increased adherence may result in greater glycemic control,

and in turn, improve outcomes and lower health care usage and
costs.

Conclusion

Extended-release metformin provides an appropriate option

for patients with type 2 DM who have GI intolerance with the
immediate-release formulation.