DIABETES AND ITS MANAGEMENT

DIABETES AND ITS MANAGEMENT
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A Major project Report on
“DIABETES AND ITS MANAGMENT”
Submitted to the
Rajiv Gandhi Proudyogik Vishwavidyalaya, Bhopal (M.P.)
With the partial Fulfilment of
BACHELOR OF PHARMACY
(2020 -2021)
Nutanben Mansukh Bhai Turakhiya Gujarati
College of pharmacy, Indore (M.P.)
Guided By: - Submitted By:-
Prof. Navin Sainy DHAWAL PAL
(7th
Semester)

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CERTIFICATE
This is to certify that the work presented in the major project entitled
For Bachelor of pharmacy
Has been carried out by DHAWAL PAL
At Nutanben Mansukh Bhai Turakhiya Gujarati college of
pharmacy
Indore,
Under the guidance of PROF. Navin Sainy
Date: - Dr. Dheeraj Jain
Place: - Indore
(Principal)
N.M.T Gujarati college of pharmacy Indore

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CERTIFICATE
This is to certify that the work presented in the major project entitled
For Bachelor of pharmacy
Has been carried out by Dhawal pal
At Nutanben MansukhBhai Turakhiya Gujarati college of
Pharmacy
Indore,
Under my guidance and to my satisfaction
Date: - Ass. Prof. Navin Sainy
Place: - Indore
(Project Guide)
N.M.T Gujarati college of pharmacy
Indore

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RECOMMENDATION
The Major project entitled “DIEBETS AND MANAGEMENT
”submitted by DHAWAL PAL is recommended and forwarded for the
partial fulfilment of B. Pharma Semester -7th
of Bachelor of pharmacy
course in Rajiv Gandhi Proudyogiki Vishwavidyalaya, Bhopal (M.P.)
Under the guidance and supervision of Ass. Prof. Navin Sainy Assistant
Professor N.M.T Gujarati college of pharmacy.
Dr. Dheeraj Jain
(Principal)
N.M.T Gujarati college of pharmacy
Indore

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ACKNOWLEDGEMENT
I express my special thanks to Shri Pankaj Bhai Sanghavi, Honourable
Secretary, shri Gujarati Samaj, Indore. For providing us excellent infrastructural
campus.
At the outset, I take this Opportunity to express my sincere gratitude to Shri
Rajesh Bhai Vyas, Chairman, N.M.T. Gujarati Collage of Pharmacy, and Indore
for giving me opportunity to pursue my major project and providing me various
ultramodern infrastructural facilities at the institute.
My sincere Thanks to Dr.Dheeraj Jain Principal. NMT Gujarati Collage of
pharmacy, Indore for his valuable support and time help.
I am honoured to express my profound and deep sense of gratitude to words my
respected guide Prof. Navin Sainy Assistant prof., N.M. T Gujarati collage of
Pharmacy, Indore. For his creative suggestion, helpful discussion, unfailing
advice, constant encouragement during the major project work. I consider my self-
privileged to have worked under his as he always shared his vast experience so
generously and patiently. I sincerely appreciate interactive help receive from his by
the way of advice or suggestion.
I am fortune to get an enormous collaboration from all our teacher Mr.Anand
Birthare, Miss Nidhi Bais, Mr. Deepak Shrivastav, Dr. Atul Joshi ,
Miss.Rashmi Rathore, Mrs.Ghazala Khan , Mrs. Ankita Dubey Gawande ,
Mrs. Anita Bhatt and all non-teaching staff to make the capable for this work.
I will be always thankful to the almighty God for giving me the strength to
carryout project work successfully
Date:-Place: - Indore DHAWAL PAL

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INDEX
S.NO TOPIC PAGE NO.
1. INTRODUCTION 1-2
2 TYPES OF DIABETAS 3
3 SING AND SYMPTOMS 4-5
4 CAUSE 6-7
5 DIAGNOSIS 8
6 PREVENTION 9
7 MANAGEMENT 10
8 TREATMENT 11
9 INSULIN 11-15
10 VARIANTES OF INSULIN 15-20
11
ORAL HYPOGLYCEMIC
AGENT
20-32
12 HERBAL TREATMENT 32-41
13 CONCULSION 42
14 REFERENCE 42-43

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INTRODUCTION
Diabetes mellitus (DM), commonly known as diabetes, is a group of metabolic
disorders characterized by a high blood sugar level over a prolonged period of time. Symptoms
often include frequent urination, increased thirst, and increased appetite. If left untreated,
diabetes can cause many complications. Acute complications can include diabetic
ketoacidosis, hyperosmolar hyper glycemic state, or death. Serious long-term complications
include cardiovascular disease, stroke, chronic kidney disease, foot ulcers, damage to the
nerves, damage to the eyes and cognitive impairment.
Diabetes is due to either the pancreas not producing enough insulin, or the cells of the body not
responding properly to the insulin produced. There are three main types of diabetes mellitus:
Specialty Endocrinology
Symptoms Frequent urination, increased thirst, increased hunger
Complications
Diabetic ketoacidosis, hyperosmolar hyperglycemic state, heart
disease, stroke, chronic kidney failure, foot ulcers, cognitive
impairment, gastroparesis
Risk factors
Type1: Family history
Type 2: Obesity, lack of exercise, genetics
Diagnostic
method
High blood sugar
Treatment Healthy diet, physical exercise
Medication Insulin, anti-diabetic medication like metformin
Frequency 463 million (8.8%)
Deaths 4.2 million (2019)

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FIG 01. PRECAUTION AGAINST DIABETS TYPE

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TYPES OF DIABETES
• Type 1 diabetes results from the pancreas's failure to produce enough insulin due to loss
of beta cells. This form was previously referred to as "insulin-dependent diabetes mellitus"
(IDDM) or "juvenile diabetes". The loss of beta cells is caused by
an autoimmune response. The cause of this autoimmune response is unknown.
• Type 2 diabetes begins with insulin resistance, a condition in which cells fail to respond to
insulin properly. As the disease progresses, a lack of insulin may also develop. This form
was previously referred to as "non insulin-dependent diabetes mellitus" (NIDDM) or "adult-
onset diabetes". The most common cause is a combination of excessive body
weight and insufficient exercise.
• Gestational diabetes is the third main form, and occurs when pregnant women without a
previous history of diabetes develop high blood sugar levels.
Comparison of type 1 and 2 diabetes
Feature Type 1 diabetes Type 2 diabetes
Onset Sudden Gradual
Age at onset Mostly in children Mostly in adults
Body size Thin or normal[39]
Often obese
Ketoacidosis Common Rare
Autoantibodies Usually present Absent
Endogenous insulin Low or absent
Normal, decreased
or increased
Concordance
in identical twins
50% 90%
Prevalence ~10% ~90%

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FIG 02. MAIN SYMPTOMS OF DIABETES.

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Signs and symptoms
The classic symptoms of untreated diabetes are unintended weight loss, polyuria (increased
urination), polydipsia (increased thirst), and polyphagia (increased hunger). Symptoms may
develop rapidly (weeks or months) in type 1 diabetes, while they usually develop much more
slowly and may be subtle or absent in type 2 diabetes.
Several other signs and symptoms can mark the onset of diabetes although they are not specific
to the disease. In addition to the known ones above, they include blurred
vision, headache, fatigue, slow healing of cuts, and itchy skin. Prolonged high blood glucose can
cause glucose absorption in the lens of the eye, which leads to changes in its shape, resulting
in vision changes. Long-term vision loss can also be caused by diabetic retinopathy. A number
of skin rashes that can occur in diabetes are collectively known as diabetic dermadromes.
FIG 03. SINGS AND SYMPTOMS OF DIABETES.

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CAUSES
Type 1
Type 1 diabetes is characterized by loss of the insulin-producing beta cells of the pancreatic
islets, leading to insulin deficiency. This type can be further classified as immune-
mediated or idiopathic. The majority of type 1 diabetes is of the immune-mediated nature, in
which a T cell-mediated autoimmune attack leads to the loss of beta cells and thus insulin. It
causes approximately 10% of diabetes mellitus cases in North America and Europe. Most
affected people are otherwise healthy and of a healthy weight when onset occurs. Sensitivity and
responsiveness to insulin are usually normal, especially in the early stages. Although it has been
called "juvenile diabetes" due to the frequent onset in children, the majority of individuals living
with type 1 diabetes are now adults.
"Brittle" diabetes, also known as unstable diabetes or labile diabetes, is a term that was
traditionally used to describe the dramatic and recurrent swings in glucose levels, often occurring
for no apparent reason in insulin-dependent diabetes. This term, however, has no biologic basis
and should not be used. Still, type 1 diabetes can be accompanied by irregular and unpredictable
high blood sugar levels, and the potential for diabetic ketoacidosis or serious low blood sugar
levels. Other complications include an impaired counterregulatory response to low blood sugar,
infection, gastroparesis (which leads to erratic absorption of dietary carbohydrates),
and endocrinopathies (e.g., Addison's disease). These phenomena are believed to occur no more
frequently than in 1% to 2% of persons with type 1 diabetes.
Type 2
Reduced insulin secretion and absorption leads to high glucose content in the blood.
Type 2 diabetes is characterized by insulin resistance, which may be combined with relatively
reduced insulin secretion. The defective responsiveness of body tissues to insulin is believed to
involve the insulin receptor. However, the specific defects are not known. Diabetes mellitus
cases due to a known defect are classified separately. Type 2 diabetes is the most common type
of diabetes mellitus. Many people with type 2 diabetes have evidence of prediabetes (impaired
fasting glucose and/or impaired glucose tolerance) before meeting the criteria for type 2
diabetes. The progression of prediabetes to overt type 2 diabetes can be slowed or reversed by

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lifestyle changes or medications that improve insulin sensitivity or reduce the liver's glucose
production.
Type 2 diabetes is primarily due to lifestyle factors and genetics. A number of lifestyle factors
are known to be important to the development of type 2 diabetes, including obesity (defined by
a body mass index of greater than 30), lack of physical activity, poor diet, stress,
and urbanization. Excess body fat is associated with 30% of cases in people of Chinese and
Japanese descent, 60–80% of cases in those of European and African descent, and 100% of Pima
Indians and Pacific Islanders. Even those who are not obese may have a high waist–hip ratio.
Dietary factors such as sugar-sweetened drinks is associated with an increased risk. The type
of fats in the diet is also important, with saturated fat and trans fats increasing the risk
and polyunsaturated and monounsaturated fat decreasing the risk. Eating white rice excessively
may increase the risk of diabetes, especially in Chinese and Japanese people. Lack of physical
activity may increase the risk of diabetes in some people.
Adverse childhood experiences (ACEs), including abuse, neglect, and household difficulties,
increase the likelihood of type 2 diabetes later in life by 32%, with neglect having the strongest
effect.
FIG 04. DIABETES RANGE.

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Diagnosis
Diabetes mellitus is characterized by recurrent or persistent high blood sugar, and is diagnosed
by demonstrating any one of the following:
• Fasting plasma glucose level ≥ 7.0 mmol/L (110 mg/dL)
• Plasma glucose ≥ 11.1 mmol/L (140 mg/dL) two hours after a 75 gram oral glucose
load as in a glucose tolerance test (OGTT)
• Symptoms of high blood sugar and casual plasma glucose ≥ 11.1 mmol/L
(200 mg/dL)
• Glycated heamoglobin (HbA1C) ≥ 48 mmol/mol (≥ 6.5 DCCT %).
A positive result, in the absence of unequivocal high blood sugar, should be confirmed by a
repeat of any of the above methods on a different day. It is preferable to measure a fasting
glucose level because of the ease of measurement and the considerable time commitment of
formal glucose tolerance testing, which takes two hours to complete and offers no prognostic
advantage over the fasting test. According to the current definition, two fasting glucose
measurements above 7.0 mmol/L (126 mg/dL) is considered diagnostic for diabetes mellitus.
WHO diabetes diagnostic criteria
Condition 2-hour glucose Fasting glucose HbA1c
Unit mmol/L mg/dL mmol/L mg/dL mmol/mol DCCT %
Normal < 7.8 < 140 < 6.1 < 110 < 42 < 6.0
Impaired fasting glycaemia < 7.8 < 140 6.1–7.0 110–125 42–46 6.0–6.4
Impaired glucose tolerance ≥ 7.8 ≥ 140 < 7.0 < 126 42–46 6.0–6.4
Diabetes mellitus ≥ 11.1 ≥ 200 ≥ 7.0 ≥ 126 ≥ 48 ≥ 6.5

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Prevention
There is no known preventive measure for type 1 diabetes. Type 2 diabetes—which accounts for
85–90% of all cases worldwide—can often be prevented or delayed by maintaining a normal
body weight, engaging in physical activity, and eating a healthy diet. Higher levels of physical
activity (more than 90 minutes per day) reduce the risk of diabetes by 28%. Dietary changes
known to be effective in helping to prevent diabetes include maintaining a diet rich in whole
grains and fiber, and choosing good fats, such as the polyunsaturated fats found in nuts,
vegetable oils, and fish. Limiting sugary beverages and eating less red meat and other sources
of saturated fat can also help prevent diabetes. Tobacco smoking is also associated with an
increased risk of diabetes and its complications, so smoking cessation can be an important
preventive measure as well.
The relationship between type 2 diabetes and the main modifiable risk factors (excess weight,
unhealthy diet, physical inactivity and tobacco use) is similar in all regions of the world. There is
growing evidence that the underlying determinants of diabetes are a reflection of the major
forces driving social, economic and cultural change: globalization, urbanization, population
aging, and the general health policy environment.
Fig. 04 Food sources

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Management
• Lifestyle
People with diabetes can benefit from education about the disease and treatment, dietary
changes, and exercise, with the goal of keeping both short-term and long-term blood glucose
levels within acceptable bounds.
• Medications
Medications used to treat diabetes act by lowering blood sugar levels. There are a number of
different classes of anti-diabetic medications. Some are available by mouth, such as metformin,
while are others are only available by injection such as GLP-1 agonists, Type 1 diabetes can only
be treated with insulin, typically with a combination of regular and NPH insulin, or synthetic
insulin analogous
• Surgery
A pancreas transplant is occasionally considered for people with type 1 diabetes who have severe
complications of their disease, including end stage kidney disease requiring kidney
transplantation.
• Support
In countries using a general practitioner system, such as the United Kingdom, care may take
place mainly outside hospitals, with hospital-based specialist care used only in case of
complications, difficult blood sugar control, or research projects. In other circumstances, general
practitioners and specialists share care in a team approach. Home telehealth support can be an
effective management technique.
Pancreas
A major portion of the pancreas* essentially comprises of glandular tissue which specially contains
acinar cells that predominantly gives rise to the secretion of certain digestive enzymes. Besides,
there
also exist some ‘isolated groups of pancreatic cells’ commonly known as the islets of
Langerhans
which usually made up of four cell types, each of which generates a distinct polypeptide
hormone,
namley :
(a) Insulin — in the beta (β) cells,
(b) Glucagon — in the alpha (α) cells,
(c) Somatostatin — in the delta (δ ) cells, and
(d) Pancreatic polypeptide — in the PP or F cell.

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Interestingly, the -cells made up 60-80% of the islets of Langerhans most predominantly and
distinctly.
FIG 06. PANCREASE
Treatment
Controlling blood sugar level or Diabetes through diet, oral medication, or insulin. Regular
screening for complication is also required.
Insulin
Insulin was discovered in 1921 by Banting and best who demonstrated the hypoglycaemic action
of an extract of pancreas prepared after degeneration of the exocrine part due to ligation of
pancreatic duct. It was first obtained in pure crystalline form in 1926 and the chemical structure
was fully worked out in 1956 by Sanger. Insulin is a two chain polypeptide having 51amino
acids and MW about 6000. The A-chain has 21 while B-chain has 30 amino acids. There are

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minor differences between human, pork and beef insulins: Thus, pork insulin is more
homologous to human insulin than is beef insulin. The A and B chains are held together by two
di sulfide bonds. Insulin is synthesized in the cells of pancreatic islets as a single chain peptide
Pre pro insulin (110 AA) from which 24 AAs are first removed to produce Proinsulin. The
connecting or ‘C’ peptide (35 AA) is split off by proteolysis in Golgi apparatus; both insulin and
C peptide are stored in granules within the cell. The C peptide is secreted in the blood along with
insulin.
FIG 07. STRUCTURE OF INSULINE.
Regulation of insulin secretion
Under basal condition ~1U insulin is secreted per hour by human pancreas. Much larger quantity
is secreted after every meal. Secretion of insulin from cells is regulated by chemical, hormonal
and neural mechanisms
Chemical The cells have a glucose sensing mechanism dependent on entry of glucose into cells
(through the aegis of a glucose transporterGLUT1) and its phosphorylation by glucokinase.
Glucose entry and metabolism leads to activation of the gluco sensor which indirectly inhibits
the ATP-sensitive K+ channel (K+ATP) resulting in partial depolarization of the cells. This

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increases intracellular Ca2+ availability (due to increased influx, decreased efflux and release
from intracellular stores) → exocytotic release of insulin storing granules. Other nutrients that
can evoke insulin release are—amino acids, fatty acids and ketone bodies, but glucose is the
principal regulator and it stimulates synthesis of insulin as well. Glucose induces a brief pulse of
insulin output within 2 min (first phase) followed by a delayed but more sustained second phase
of insulin release.
Hormonal A number of hormones, e.g. growth hormone, corticosteroids, thyroxine modify
insulin release in response to glucose. PGE has been shown to inhibit insulin release. More
important are the intra-islet paracrine interactions between the hormones produced by different
types of islet cells. The cells constitute the core of the islets and are the most abundant cell type.
The cells, comprising 25% of the islet cell mass, surround the core and secrete glucagon. The α
cells(5–10%) elaborating somatostatin are interspersed between the cells. There are some PP
(pancreatic polypeptide containing) cells as well.
• Somatostatin inhibits release of both insulin and glucagon.
• Glucagon evokes release of insulin as well assomatostatin.
• Insulin inhibits glucagon secretion. Amylin, another cell polypeptide released with insulin,
inhibits glucagon secretion through a central site of action in the brain.
The three hormones released from closely situated cells influence each other’s secretion and
appear to provide fine tuning of their output in response to metabolic needs
FIG 08. REGULATION OF INSULINE.

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Neural The islets are richly supplied by sympathetic and vagal nerves.
• Adrenergic 2 receptor activation decreases insulin release (predominant) by inhibiting
cell adenylyl cyclase.
• Adrenergic 2 stimulation increases insulin release (less prominent) by stimulating cell
adenylyl cyclase.
• Cholinergic—muscarinic activation by ACh or vagal stimulation causes insulin secretion
through IP3/DAG-increased intracellular Ca2+ in the cells. These neural influences appear to
govern both basal as well as evoked insulin secretion, because the respective blocking agents
have effects opposite to that mentioned above. The primary central site of regulation of insulin
secretion is in the hypothalamus: stimulation of ventrolateral nuclei evokes insulin release,
whereas stimulation of ventromedial nuclei has the opposite effect.
Mechanism of action Insulin acts on specific receptors located on the cell membrane of
practically every cell, but their density depends on the cell type: liver and fat cells are very rich.
The insulin receptor is a receptor tyrosine kinase (RTK) which is hetero tetrameric glycoprotein
consisting of 2 extracellular and 2 transmembrane subunits linked together by disulfied bonds. It
is oriented across the cell membrane as a heterodimer. The α β subunits carry insulin binding
sites, while the subunits have tyrosine protein kinase activity. Binding of insulin to α β subunits
induces aggregation and internalization of the receptor along with the bound insulin molecules.
This activates tyrosine kinase activity of the subunits pairs of subunits phosphorylate tyrosine
residue son each other expose the catalytic site to phosphorylate tyrosine residues of Insulin
Receptor Substrate proteins (IRS1,IRS2, etc). In turn, a cascade of phosphorylation and
dephosphorylation reactions is set into motion which amplifies the signal and results in
stimulation or inhibition of enzymes involved in the rapid metabolic actions of insulin. Certain
second messengers like phosphatidyl inositol trisphosphate (PIP3) which are generated through
activation of a specific PI3-kinase also mediate the action of insulin on metabolic enzymes.

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FIG 09. INSULIN AND ITS RECEPTOR
Variants of Insulin Products
There are a number of variants of insulin products that are available as a ‘drug’ Insulin
Injection[Synonyms : Regular Insulin ; Crystalline Zinc Insulin]
It is available as a sterile, acidified or neutral solution of insulin. The solution has a potency
of40, 80, 100 or 500 USP Insulin Units in each ml. Mechanism of Action. It is a rapid-action
insulin. The time interval from a hypodermic injection of this ‘drug’ until its action may be
observed ranges between 1/2 to 1 hour. It has been observed that the duration of action is
comparatively short but evidently a little longer than the plasma half-life that stand sat nearly 9
minutes. Importantly, the duration of action is not linearly proportional to the size of the dose,
but it is a simple function of the logarithm of the dose i.e., if 1 unit exerts its action for 4 hours
then 10units will last 8 hours. In usual practice the duration is from 8 to 12 hour after the
subcutaneous injection, which is particularly timed a few minutes before the ingestion of food so
as to avoid any possible untoward fall in the prevailing blood-glucose level.
Isophane Insulin Suspension
[Synonyms : Isophane Insulin ; Isophane Insulin Injection ; NPH Insulin ; NPH Iletin;] :

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The ‘drug’ is a sterile suspension of Zinc-insulin crystals and protamine sulphate in buffered
water for injection, usually combined in such a fashion that the ‘solid phase of the suspension’
essentially comprises of crystals composed of insulin, protamine*, and zinc.
Each mL is prepared from enough insulin to provide either 40, 80, or 100 USP Insulin units of
insulin activity.
Mechanism of Action. The ‘drug’ exerts its action as an intermediate-acting insulin for being
insoluble and obtained as repository form of insulin. In reality, the action commences in 1–1.5
hour, attains a peak-level in 4 to 12 hour, and usually lasts upto 24 hours, with an exception that
‘human isophane insulin’ exerts a rather shorter duration of action. It is, however, never to be
administered IV.
Note : Incidence of occasional hypersensitivity may occur due to the presence of
‘protamine’.
Insulin Zinc Suspension
It is invariably obtained as a sterile suspension of insulin in buffered water for injection,
carefully modified by the addition of zinc chloride (ZnCl2) in such a manner that the ‘solid-
phase of the suspension’ comprises of a mixture of crystalline as well as amorphous insulin
present approximately in a ratio of7 portions of crystals and 3 portions of amorphous substance.
Each mL is obtained from sufficientinsulin to provide either 40, 80, or 100 USP Insulin Units of
the Insulin Activity.
Mechanism of Action. It has been duly observed that the ‘amorphous zinc-insulin component’
exerts a duration of action ranging between 6–8 hours, whereas the ‘crystalline zinc-insulin
component ’a duration of action more than 36 hour, certainly due to the sluggishness and
slowness with which the larger crystals get dissolved. However, an appropriate dosage of the 3 :
7 mixture employed usually displays an onset of action of 1 to 2.5 hour and an intermediate
duration of action which is very near to that of ‘isophane insulin suspension’ (24 hour), with
which preparation this ‘drug’ could be employed interchangeably without any problem
whatsoever. However, it must not be administered IV.
Note : The major advantage of ‘zinc insulin’ is its absolute freedom from ‘foreign protein
matter’, such as :globin, or protamine, to which certain subjects are sensitive.
Extended Insulin Zinc Suspension
[Synonyms : Ultra-Lente Iletin ; Ultralente Insulin/ Ultratard]
Mechanism of Action :The actual ‘crystalline profile’ in this specific form are of sufficient
size to afford a slow rate of dissolution. It is found to exert its long-acting action having an onset
of action ranging between 4 to 8 hours, an optimal attainable peak varying between 10-30 hours,
and its overall duration of action normally in excess of 36 hours, which being a little longer than
that of Protamine Zinc Insulin.
Note : Because the ‘drug’ is free of both protamine and other foreign proteins, the eventual
incidence of allergic reactions gets minimized to a significant extent.

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Prompt Insulin Zinc Suspension
[Synonyms : Semi-Lente Iletin ; Semitard]
The ‘drug’ is usually a sterile preparation of insulin in ‘buffered water for injection’,
strategically modified by the addition of zinc chloride (ZnCl2) in such a manner that the ‘solid
phase of the prevailing suspension’ is rendered amorphous absolutely. Each mL of this
preparation provides sufficient insulin either 40, 80, or 100 USP Insulin Units.
Mechanism of Action. The zinc-insulin in this particular form is a mixture of amorphous and
extremely fine crystalline materials. As a result, the ‘drug’ serves as a rapid-acting insulin with
an onset of 1 to 1.5 hour, an attainable peak of 5-10 hours, and a duration of action ranging
between 12-16 hours.
Note : Since this specific form of insulin is essentially free of any foreign proteins, the
incidence of allergic reactions is found to be extremely low.
Lispro Insulin
[Synonyms : Human Insulin Analog ; Humalog] : It is a human insulin analogue of r DNA
origin meticulously synthesized from a special non pathogenic strain of E. coli, genetically
altered by the addition of the gene for insulin lispro ; Lys (B28), Pro (B29). In fact, the
prevailing amino acids at position 28 and 29 of human insulin have been reversed altogether.
Mechanism of Action. The ‘drug’ is a very rapid-acting insulin which may be injected
conveniently just prior to a meal. It exhibits an onset of action within a short span of 15 minutes
besides having a relatively much shorter peak ranging between 0.5 to 1.5 hour, and having
duration of action varying between 6 to 8 hours in comparison to the ‘regular insulin injection’.
Protamine Zinc Insulin Suspension
[Synonyms :Zinc Insulin ; Protamine Zinc Insulin Injection ; Protamine Zinc and Iletin;] :
The ‘drug’ is a sterile suspension of insulin in buffered water for injection, that has been
adequately modified by the addition of zinc chloride (ZnCl2) and protamine sulphate. The
protamine sulphate is usually prepared from the sperm or from the mature testes of fish
belonging to the genus Oncorhynchus Suckley or Salmo Linne (Family :Salmonidae). Each mL
of the suspension prepared from sufficient insulin to provide wither 40, 80, or 100 USP Insulin
Units.
Mechanism of Action. The ‘drug’ exerts a long-acting action having an onset of action of 4 to 8
hour, a peak at 14 to 24 hour, and a duration of action nearly 36 hour. As a result this ‘drug’
need not be administered with any definite time relation frame to the corresponding food intake.
Besides, it should not be depended upon solely when a very prompt action is required, such as :
in diabetic acidosis and coma. Since the ‘drug’ possesses an inherent prolonged action, it must
not be administered more frequently than once a day. It has been duly observed that ‘low levels’
invariably persists for 3 o 4 days ; and, therefore, the dose must be adjusted at intervals of not
less than 3 days. It is given by injection, normally into the loose subcutaneous tissue.

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Insulin resistance
Insulin resistance refers to suboptimal response of body tissues, especially liver, skeletal muscle
and fat to physiological amounts of insulin. As already stated, relative insulin resistance is
integral to type 2 DM. Advanced age, obesity and sedentary life-style promote insulin resistance.
Insulin sensitivity has been found to decline with age. Glucose entry into muscle and liver in
response to insulin is deficient in individuals with large stores of body fat. Bigger adipocytes
have fewer insulin receptors. However, in most type 2 diabetics the transducer mechanism
linking insulin receptor to the response appears to be faulty, rather than the receptor itself.
Exercise increases insulin sensitivity and lack of it contributes to insulin resistance. Pregnancy
and oral contraceptives often induce relatively low grade and reversible insulin resistance. Other
rare causes are—acromegaly, Cushing’s syndrome, pheochromocytoma, lipoatrophic diabetes
mellitus. Hypertension is often accompanied with relative insulin resistance as part of metabolic
syndrome.
Acute insulin resistance This form of insulin resistance develops rapidly and is usually a short
term problem. Causes are—
(a) Infection, trauma, surgery, emotional stress induce release of corticosteroids and other
hyperglycaemic hormones which oppose insulin action.
(b) Ketoacidosis—ketone bodies and FFA inhibit glucose uptake by brain and muscle. Also
insulin binding may increase resulting in insulin resistance. Treatment is to overcome the
precipitating cause and to give high doses of regular insulin. The insulin requirement comes back
to normal once the condition has been controlled.

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Treatment is to overcome the precipitating cause and to give high doses of regular insulin. The
insulin requirement comes back to normal once the condition has been controlled.
Newer insulin delivery devices A number of innovations have been made to improve ease and
accuracy of insulin administration as well as to achieve tight glycaemia control. These are:
1. Insulin syringes Prefilled disposible syringes contain specific types or mixtures of regular and
modified insulins.
2. Pen devices Fountain pen like: use insulin cartridges for s.c. injection through a needle. Preset
amounts (in 2 U increments) are propelled by pushing a plunger; convenient in carrying and
injecting.
3. Inhaled insulin An inhaled human insulin preparation was marketed in Europe and the USA,
but withdrawn due to risk of pulmonary fibrosis and other complications. Thefine powder
delivered through a nebulizer controlled mealtime glycaemia, but was not suitable for round-the-
clock basal effect. Attempts are being made to overcome the shortcomings.
4. Insulin pumps Portable infusion devices connected to a subcutaneously placed cannula—
provide ‘continuous subcutaneous insulin infusion’ (CSII). Only regular insulin or a fast acting
insulin analogue is used. The pump can be programmed to deliver insulin at a low basal rate
(approx. 1 U/hr) and premeal boluses (4–15 times the basal rate) to control post-prandial
glycaemia. Though, theoretically more appealing, no definite advantage of CSII over multidose
s.c. injection has been demonstrated. Moreover, cost, strict adherence to diet, exercise, care of
the device and cannula, risk of pump failure, site infection, are too demanding on the patient. The
CSII may be appropriate for selected type 2 DM cases only.
5. Implantable pumps Consist of an electromechanical mechanism which regulates insulin
delivery from a percutaneously refillable reservoir. Mechanical pumps, propellant driven and
osmotic pumps have been utilized.
6. Other routes of insulin delivery Intraperitoneal, oral (by complexing insulin into liposomes or
coating it with impermeable polymer) and rectal routes are being tried. These have the advantage
of providing higher concentrations in the portal circulation, which is more physiological
Adverse effect of insulin.
• Hypoglycemia
• Allergic reaction
• Lipodystrophy
• Insulin resistance
• Hypokalemia
• Weight gain
• Difficult to admistration

20
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Oral Hypoglycemic Agent
The synthetic oral hypoglycemic agents have been added to the therapeutic armamentarium
over the last five decades in lieu of the various ‘insulin variants’ discussed earlier. In this
particular section the focus shall be made on the different categories of synthetic oral hypo
glycemic agents based on their chemical structures, namely :
(i) Sulfonylureas,
(ii) Non sulfonylureas,
(iii) Thiazolindiones,
(iv) Biguanides, and
(v) α-Glucosidase Inhibitors
The important ‘drugs’ belonging to each of the above categories shall now be discussed
individually in the sections that follows
Sulfonylureas
The sulfonylurea hypoglycemic agents are basically sulphonamide structural analogues but
they do not essentially possess any ‘antibacterial activity’ whatsoever. In fact, out of 12,000
sulfonylureas have been synthesized and clinically screened, and approximately 10 compounds
are being used currently across the globe for lowering blood-sugar levels significantly and safely.
The sulfonylureas may be represented by the following general chemical structure :
1-[(p-Acetylphenyl) Sulfonyl]-3-cyclohexyl urea ; USP ;
Dymelor(R) ;
It lowers the blood-sugar level particularly by causing stimulation for the release of endogenous
insulin.
Mechanism of Action. The ‘drug’ gets metabolized in the liver solely to a reduced entity, the
corresponding -hydroxymethyl structural analogue, which is present predominantly in
humans, shares the prime responsibility for the ensuing hypoglycemic activity.
SAR of Acetohexamide. It is found to be an intermediate between ‘tolbutamide’ and
‘chlorpropamide’ i.e., in the former the cyclohexyl ring is replaced by butyl moiety and p-
acetyl group with methyl group ; while in the latter the cyclohexyl group is replaced by propyl
moiety and the p-acetyl function with chloro moiety.

21
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Chlorpropamide
1-[(p-Chlorophenyl)-Sulphonyl]-3-propyl urea ;
Diabinese(R) ;
Synthesis
p-Chlorobenzene Propylisocyanate Chlorpropamide Sulphonamide The interaction between p-
chlorobenzenesulphonamide and phenyl isocyanate in equimolar concentrations under the
influence of heat undergoes addition reaction to yield the desired official compound. The
therapeutic application of this ‘drug’ is limited to such subjects having a history of stable, mild
to moderately severe diabetes melitus who still retain residual pancreatic -cell function to a
certain extent.
Mechanism of Action. The ‘drug’ is found to be more resistant to conversion to its
corresponding inactive metabolites than is ‘tolbutamide’ ;and, therefore, it exhibits a much
longer duration of action. It has also been reported that almost 50% of the ‘drug’ gets usually
excreted as metabolites, with the principal one being hydroxylated at the C-2 position of the
propyl-side chain.
Tolazamide
1-(Hexahydro-1H-azepin-1-yl)-3-(p-tolylsulphonyl) urea ;
Tolinase(R) ;

22
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It is found to be more potent in comparison to ‘tolbutamide’, and is almost equal in potency to
chlorpropamide.
Mechanism of Action. Based on the radiactive studies it has been observed that nearly 85% of
an oral dose usually appears in the urine as its corresponding metabolites which were certainly
more water-soluble than the parent tolazamide itself.
Tolbutamide
Benzenesulphonamide, N-[(butylamino) carbonyl]-4-methyl- ;
Orinase(R) ;
Synthesis
First of all toluene is treated with chlorosulfonic acid to yield p-toluenesulphonyl chloride, which
on treatment with ammonia gives rise to the formation of p-toluenesulphonamide. The resulting
product on condensation with ethyl chloroformate in the presence of pyridine produces N-p-
toluenesulphonyl carbamate with the loss of a mole of HCl. Further aminolysis of this product
with butyl amine using ethylene glycol monomethyl ether as a reaction medium loses a mole of
ethanol and yields tolbutamide. It is mostly beneficial in the treatment of selected cases of non-
insulin-dependent diabetes melitus (NIDDM). Interestingly, only such patients having some
residual functional islet -cells which
may be stimulated by this drug shall afford a positive response. Therefore, it is quite obvious that
such subjects who essentially need more than 40 Units of insulin per day normally will not
respond to this drug.
Mechanism of Action. The ‘drug’ usually follows the major route of breakdown ultimately
leading to the formation of butylamine and p-toluene sulphonamide respectively.
Importantly, the observed hypoglycemia induced by rather higher doses of the ‘drug’ is mostly
not as severe and acute as can be induced by insulin ;and, therefore, the chances of severe
hypoglycaemic reactions is quite lower with tolbutamide ; however, one may observe acute
refractory hypoglycaemia occasionally does take place. In other words, refractoriness to it often
develops.

23
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Second-Generation Sulfonylureas
The vital and important members of this class of compounds are, namely :Glipizide ; Glyburide
; and Glumepiride. These drug substances will be dealt with separately in the sections that
follows :
Glipizide
Pyrazinecarboxamide, N-[2-[4-[[[(cyclohexylamino) carbonyl] amino] sulfonyl] ethyl]-5-methyl-
; Glucotrol(R)' ;
Synthesis
Glipizide may be prepared by the condensation of 4-[2-(5-methyl-2-pyrazine-carboxamido)-
ethyl] benzenesulphonamide with cyclohexylisocyanate in equimolar proportions.
It is employed for the treatment of Type 2 diabetes mellitus which is found to be 100 folds more
potent than tolbutamide in evoking the pancreatic secretion of insulin. It essentially differs from
other oral hypoglycemic drugs wherein the ensuing tolerance to this specific action evidently
does not take place.
Mechanism of Action. The primary hypoglycemic action of this ‘drug’ is caused due to the fact
that it upregulates the insulin receptors in the periphery. It is also believed that it does not exert a
direct effect on glucagon secretion. The ‘drug’ gets metabolized via oxidation of the
cyclohexane ring to the corresponding p-hydroxy and m-hydroxy metabolites. Besides, a ‘minor
metabolite’ which occurs invariably essentially involves the N-acetyl structural analogue that
eventually results, from the acetylation of the primary amine caused
due to the hydrolysis of the amide system exclusively by amidase enzymes.
Note : The ‘drug’ enjoys two special status, namely :
(a) Treatment of non-insulin dependent diabetes mellitus (NIDDM) since it is effective
in most patients who particularly show resistance to all other hypoglycemicdrugs ;
and
(b) Differs from other oral hypoglycemic drug because it is found to be more effective
during eating than during fasting.

24
NMTGCOP
Glyburide
Benzamide, 5-chloro-N-[2-[4-[[[(Cyclohexylamino) carbonyl] amino] sulphonyl] phenyl] ethyl]-
2-methoxy- ; Dia Beta(R) ;Glynase Press Tab(R) ; Micronase(R) ;
It is mostly used for Type 2 diabetes melitus. It is found to be almost 200 times as potent as
tolbutamide in evoking the release of insulin from the pancreatic islets. However, it exerts a
rather more effective agent in causing suppression of fasting than postprandial hyperglycemia.
Mechanism of Action. The ‘drug’ gets absorbed upto 90% when administered orally from an
empty stomach. About 97% gets bound to plasma albumin in the form of a weak-acid anion ;
and, therefore, is found to be more susceptible to displacement by a host of weakly acidic drug
substances. Elimination is mostly afforded by ‘hepatic metabolism’. The half-life ranges between
1.5 to 5 hours, and the duration of action lasts upto 24 hours.
SAR of Glyburide. The SAR of Glyburide and Glypizzideare discussed below :
DRUG pKa Potency Compared to Tolbutamide
Glipizide 5.9 100 times more potent
Glyburide 5.3 200 times more potent
Obviously the presence of ‘R’ in glyburide potentiates the hypoglycemic activity 200 times,
whereas the heterocylic nucleus in glipizide potentiates 100 times in comparison to tolbutamide.

25
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Glimepiride
1-[[p-[2-(3-Ethyl-4-methyl-2-oxo-3-pyrroline-1-carboxamido) ethyl] phenyl] sulphonyl]-3
(trans- 4-methylcyclohexyl) urea ; Amaryl(R) ;
Its hypoglycemic activity is very much akin to glipizide.
Mechanism of Action. The ‘drug’ is found to be metabolized primarily through oxidation of the
alkyl side chain attached to the pyrrolidine nucleus via a minor metabolic path that essentially
involves acetylation of the amine function. SAR of Glimepiride. The only major distinct
difference between this ‘drug’ and glipizide is that the former contains a five-membered
‘pyrrolidine ring’ whereas the latter contains a six-membered ‘pyrazine ring’.
Non-Sulfonylureas-Metaglinides
Metaglinidesare nothing but non sulphonylurea oral hypoglucemic agents normally employed
in the control and management of type 2 diabetes (i.e., non-insulin-dependent diabetes
mellitus, NIDDM). Interestingly, these agents have a tendency to show up a quick and rapid
onset and a short duration of action. Just like the ‘sulphonylureas’, they also exert their action
by inducing insulinrelease from the prevailing functional pancreatic α-cells. Importantly, the
mechanism of action of the ‘metaglinides’ is observed to differ from that of the
‘sulphonylureas’. In fact, the mechanism of action could be explained as under :
(a) through binding to the particular receptors in the -cells membrane that ultimately lead to
the closure of ATP-dependent K+ channels, and
(b) K+ channel blockade affords depolarizes the -cell membrane, which iN turn gives rise to
Ca2+ influx, enhanced intracellular Ca2+, and finally stimulation of insulin secretion.
Based on the altogether different mechanism of action from the two aforesaid ‘sulphonylureas’
there exist two distinct, major and spectacular existing differences between these two apparently
similar categories of ‘drug substances’, namely :
(i) Metaglinidesusually produe substantially faster insulin production in comparison to the
‘sulphonyl ureas’, and, therefore, these could be administered in-between meals by virtue
of the fact that under these conditions pancreas would produce insulin in a relatively much
shorter duration, and
(ii) Metaglinidesdo not exert a prolonged duration of action as those exhibited by the
‘sulphonylureas’. Its effect lasts for less than 1 hour whereas sulphonylureascontinue to
cause insulin generation for several hours.

26
NMTGCOP
Repaglinide
p-Toluic acid, (+)-2-ethoxy- -[[(S)- -isobutyl-o-piperidino-benzyl] carbamoyl]- ;
Prandin(R) ;
It is used in the control and management of Type-2 diabetes mellitus. It must be taken along
with meals.
Mechanism of Action. The ‘drug’ is found to exert its action by stimulating insulin secretion
by binding to and inhibiting the ATP-dependent K+ channels in the -cell membrane, resulting
ultimately in an opening of Ca2+ channels. It gets absorbed more or less rapidly and completely
from the GI tract; and also is exhaustively metabolized in the liver by two biochemical
phenomena, such as :
(a)glucuronidation ; and (b) oxidative biotransformation. Besides, it has been established that the
hepatic cytochrome P-450 system 3A4 is predominantly involved in the ultimate metabolism of
repaglinide. However, this specific metabolism may be reasonably inhibited by certain drug
substances’, for instance: miconazole, ketoconazole, and erythromycin.
Nateglinide

27
NMTGCOP
N-(4-Isopropylcyclohexanecarbonyl)-D-phenylalanine ; Starlix(R) ;
It is a phenylalanine structural analogue and belongs to the class of ‘metaglinides’. It is mostly
employed in the control and management of type 2 diabetes.
Thiazolindiones
The thiazolindiones exclusively designate a distinct and novel non sulphonyl urea group of
potent hypoglycemic agents that are used invariably for the treatment of NIDDM. However,
these ‘drugs’ essentially needs a ‘functioning pancreas’ which may give rise to the reasonably
adequate secretion of insulin from -cells, very much akin to the sulphonyl ureas. It has been
observed duly that insulin may be released in ‘normal levels’ from the -cells ; however, the
peripheral sensitivity to this particular hormone may be lowered appreciably. It has been amply
established that ‘thiazolindiones’ are highly selective agonists for the peroxisome proliferator-
activated receptor-r (PPARr), that is primarily responsible for improving ‘glycemic control’
exclusively via the marked and pronounced efficacy of insulin sensitivity in the adipose tissue
and muscles. Besides, they also prevent and inhibit the prevailing hepatic gluconeogenesis. In
short, one may add that thiazolindiones invariably help to normalize blood-sugar level in two
ways : (a) through glucose metabolism ; and (b) through reduction of the amount of insulin
required to accomplish glycemic control.
Rosiglitazone
( )-5-[[4-[2-(Methyl-2-pyridinylamino) ethoxy] phenyl] methyl]-2, 4-thiazolidinedione ;
Avandia(R) ;
The ‘drug’ has a single chiral centre (marked ) ; and, therefore, exists as a racemate.
Importantly, the enantiomers are found to be ‘absolutely indistinguishable’ by virtue of their
rapid interconversion.

28
NMTGCOP
Troglitazone
2, 4-Thiazolidinedione, ( )-5-[[4-[3, 4-dihydro-6-hydroxy-2, 5, 7, 8-tetramethyl-2H-1-
benzopyran- 2-yl) methoxy] phenyl] methyl]- ; Rezulin(R) ;
The ‘drug’ improves the responsiveness to insulin in such patients that experience Type 2
diabetes mellitus problems of insulin resistance initiated and sustained by a ‘unique
mechanism of action’ which is fairly comparable with those of other similar drugs. Importantly,
it is at present only approved for use with insulin.
Mechanism of Action. The ‘drug’ exerts its action by decreasing blood glucose in diabetic
patients having hyperglycemia by improving target organ response to insulin. Besides, in the
presence of both exogenous and endogenous insulin the ‘drug’ minimizes the hepatic glucose
output, enhances insulin-dependent glucose uptake, and finally lowers fatty acid output in
adipose tissue. It also gets bound to the nuclear receptors usually termed as peroxisome
proliferator-activated receptors (PPARs) which predominantly regulate solely the
transcription of a host of insulin-responsive genes that are found to be critical to ‘glucose’ and
‘lipid’ metabolism.
Troglitazone is highly bound (> 99%) to serum albumin. It gets metabolized solely in the liver
to several inactive compounds, including a sulphate-conjugate—a major metabolite, and mostly
excreted in the faeces.
Biguanides
The medicinal compounds included in this classification essentially comprise of two ‘guanidine
residues ’joined together. A few typical examples belonging to this category,
namely ;metformin, phenformin, are described as under :

29
NMTGCOP
Metformin Hydrochloride
Imidodicarbenimidic diamide, N, N-dimethyl-, monohydrochloride ;
Glucophage(R) ;Metiguanide(R) ;
It is used as an oral antihyperglycemic drug for the management of Type 2 diabetes mellitus. It
is invariably recommended either as monotherapy or as an adjunct to diet or with a sulphonyl
urea (combination) to reduce blood-glucose levels.
Mechanism of Action. The ‘drug’ is found to lower both basal and postprandial glucose.
Interestingly, its mechanism of action is distinct from that of sulphonyl urea and does not cause
hypoglycemia. However, it distinctly lowers hepatic glucose production, reduces intestinal
absorption of glucose, and ultimately improves insulin sensitivity by enhancing appreciably
peripheral glucose uptake and its subsequent utilization. The ‘drug’ is mostly eliminated
unchanged in the urine, and fails to undergo hepatic metabolism.
Phenformin
The ‘drug’ is obsolete nowadays.
Glucosidase Inhibitors
It is quite well-known that the specific enzyme -glucosidase is strategically located in the
brush-border of the small intestine ; and, is exclusively responsible for affording cleavage of the
dietary carbohydrates and thereby augmenting their rapid absorption into the body. Therefore,
any means by which the inhibition of this enzyme is affected would certainly permit less-dietary
carbohydrate to be available for absorption ; and, hence, less available in the blood-stream soon
after ingestion of an usual meal. It has been observed that the prevailing inhibitory characteristic
features of such agents are maximum for glycoamylase, followed by sucrose, maltase and
dextranase respectively. A few classical examples are discussed below :

30
NMTGCOP
Acarbose
Glucose, o-4, 6-dideoxy-4-[[[15-(1 , 4 , 5(3, 6 )]-4, 5, 6-trihydroxy-3-(hydroxymethyl)-2-
cyclohexen-1-yl] amino]- -o-glucopyranosyl-(1-4)-o- -D-glucopyranosyl-(1-4)- ;
Precose (R) ;
It is used in the control and management of Type 2 diabetes mellitus.
Mechanism of Action. The ‘drug’, which is obtained from the microorganism Actinoplanes
utahensis, is found to a complex oligosaccharide that specifically delays digestion of indigested
carbohydrates, thereby causing in a smaller rise in blood glucose levels soonafter meals. It fails
to increase insulin secretion ; and its antihyperglycemic action is usually mediated by a sort of
competitive, reversible inhibition of pancreatic -amylase membrane-bound intestinal -
glucosidase hydrolase enzymes. The ‘drug’ is metabolized solely within the GI tract, chiefly by
intestinal bacteria but also by diagestive enzymes.
Miglitol
1-(2-Hydroxyethyl)-2-(hydroxy-methyl)-[2R-(2, 3, 4, 3)]-piperidine ;

31
NMTGCOP
Glyset (R) ; It also lowers blood-glucose level.
Mechanism of Action. It resembles closely to a sugar, having the heterocyclic nitrogen serving
as an isosteric replacement of the ‘sugar oxygen’. The critical alteration in its structure enables
its recognition by the α-glycosidase as a substrate. The ultimate outcome is the overall
competitive inhibition of the enzyme which eventually delays complex carbohydrate absorption
from the ensuing GI tract.

32
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Adverse effect of oral hypoglycemic agents.
1. Feeling dizzy
2. Drowsy
3. Having heart burn
4. Being sick
5. Feeling sick
6. Having stomach pain
7. Constipation
8. Frequently urination
HERBAL DRUG TREATMENT FOR DIEBETIS
Role of insulin and glucagon Glycogen synthesized, stored and secreted by the alpha-cells of
islets of langerhans. Glucose is the major regulator of glucagons secretion, hyperglycemia
inhibits while hypoglycemia stimulate the release or glucagons. The release of insulin form the
beta cells of pancreas is stimulated by increase blood glucose level. Thus, glucagons and insulin
is mutually antagonist to each other in functions. Herbal drug with antidiabetic activity from
ancient period, peoples are using herbal plants as home remedies for treatment of diabetes. The
treatment is design to control Glucose level in blood. This is the immediate goal, which is to
stabilize the blood sugar and eliminate the symptoms of high blood sugar. The long-term goals
o9f herbal treatments are to prolong life, improve the quality of life, relieve symptoms, and
prevent complications. The main advantage of herbal drug is that, it is safer and cured disease
with less side effect and have safer than synthetic drug. Some of the herbal used for treatment of
diabetes are as follows:
Table 1: Some herbal plants with Antidiabetic activity.
S. No. Name Biological Name Family Part used for
activity
1 Agrimony Agrimonia eupatoria L. Rosaceae. Herb.
2 Alfalfa
Medicago sativa L.
Fabaceae. Herb.
3 Aloe vera
Aloe barbadensis
Liliaceae. Leaves.
4 Burdock
Arctium lappa L.
Asteraceae. Root.
5 Celery
Apium graveolens L.
Apiaceae Fruit.

33
NMTGCOP
6 Cornsilk
Zea mays L.
Gramineae Stigma, Style.
7 Damiana
Tumera diffusa Willd.
Turneraceae Leaf, Stem
8 Dandelion
Taraxacum officinale Weber.
Asteraceae Leaf, root.
9 Elecampne
Inula helenium L.
Asteraceae Rhizome, Root.
10 Eucalyptus
Eucalyptus globules Labill.
Myraceae Leaf.
11 Fenugreek
Trigonella foenum-graecum
L. Leguminosae. Seed.
12 Garlic
Allium sativum L.
Amaryilidaceae Bulb (clove)
13 Ginger
Zingiber officinaie
Zingiberaceae. Rhizome.
14 Gindeng
panax
Panex species; P.ginseng
Meyer, P.quinquefclius L.
Araliaceae. Root.
15 Ispaghula
Plantago ovata Forsk.
Plantaginaceae. Seed, husk.
16 Java tea Orthosiphon stamineus
Benth.
Lamiaceae.
Dried
leaves,Stems.
17 Juniper
Juniperus communis L.
Pinaceae Fruits (Berry).
18 Marshmallow
Althaea officinalis L.
Malvaceae. Leaf, Root.
19 Myrrh Xommiphora molmol;
C.abyssinca eng
Bursuraceae Oleo-gum-resin
20 Nettle
Urtica dioica L.
Urticaceae Herb.
21 Sage
Salvia officinalis L.
Labiatae Leaf.
22 senega
Polygala senega L.
Polygalaceae Root
23 Tansy
Tanacetum vulgare L
Asteraceae Herb.

34
NMTGCOP
Table 2: Chemical Composition and other Biological Activity:
S. No. Name Chemical Constituents Biological Activity
1 Agrimony Apiginin, lutiolin,
ellagitannin, Quercitrin,
ursolic acid.
Astringent: colitis;
diuretic; diarrhea; cystitis.
2 Alfalfa Malonic acid, trigonellinge,
arginine, medicagol,
genistein, campesterol,
Bcarotene
Arthritis; peptic ulce,
bactericidal; emetic;
cardiatonic; diuretic.
3 Aloe Vera Pentocides-Barbaloin, aloin,
isobarbaloin, betabarbaloin.
Catharatic; Prgative;
Constipation.
4 Burdock
Fukinone, B-setolone, resin,
B-inesmol, myristic,
rutaretin.
Gout; rheumatism;
diuretic; eczema; psoriasis.
5 Celery
Apiginin, apigravin, celerin,
B-eudesmol, myristic,
rutaretin.
Antirhrumatic; sedative;
urinary antiseptic; gout,
rheurnatold arthritis;
diuretic
6 Corn silk Linoleic, oieic, palrnitic
acid,
phytosterols, pigments,
vitamin(C&K)
Diuretic; stone reducing
properties; noctumal
enuresis; prostatitis; acute
and chronic inflammation.
7 Damiana Tetrraphyline B, calamine,
1-
8-cineole,B-copaene,
arbutin.
Antidepressant;
thomopetic, mild
purgative; stomachic;
aphrodisiac properties.
8 Dandelion Cichoric acid, aesculin,
lueteolin-7-diglucoside, oieic
acid, onocafferyl tartaric
acid.
Gllstone: diuretic laxative;
cholechstitis; Jaundic;
atonic dysphasia.
9 Elecampane B and y- sitosterol,
stigmasterol, friedelin,
alantic acid, azulene.
Expectorant; antitussive;
diaphoretic; bactericidal;
pulmonary tuberculosis.

35
NMTGCOP
10 Eucalyptus Citronellal, citronellol
Bpinene, p-cymene cineole,
linallol.
Antibacterial;
Antiinflammatory.
11 Fenugreek
Gentianine, trigonelline,
choline, tigogenin.
Mucilaginous demulcent;
laxative; nutritive;
expectorant.
12 Garlic Allinase, peroxidase,
myrosinase, aliyipropyl
disulfide, ajoene,
sallylmercapotcysteine.
Diaphoretic, expectorant,
antispasmotic, antiseptic,
antiviral, hypotensive,
Anthelmintic.
13 Ginger Starch, palmitic acid, oleic
acid, linolenic acid, caprylic
acid, arachidic cid,
zingerone, zindiberol.
Carminative, diaphoretic,
antispasmodin.
14 Ginseng panax Protopanaxadiol,
protopanaxatriol, panacene,
limonene, terpineol.
Thymoleptic,
sedative,demulcent,
stomachic, Aphrodisiac.
15 Ispaghula Boschniakine, boschinakinic
acid, aucubin, placteose,
priterpine.
Demulcent, laxative.
16 Java tea Orthochromene,
methylripariochromene,
acetovanillochromene,
Dieterpenes, ß-elemene,
βcaryophyllene.
Hypertension, diabetes.
17 Juniper
Diterpene acids, ascprbic
acid, glucurosnic acid,
Diuretic, antispasmodic,
carminative, stomachic,
amento- flavone,
proanthocyanidins.
antirhumatic.
18 Marshma-llow Arabinas, glucans,
arabinogalactans,isoscutellari n,
ferulic, syringin.
Demulcent,
expectorant,Emollient,
direritcs; Antilithic.
19 Myrrh Arabinose, galactose, ά-, β-, γ-
commiphoric acid,
commiphorinic acid.
Anitimicrobial, astringent,
carminative; Expectorant,
antiseptic anticatarrhal.

36
NMTGCOP
20 Nettle Carbonic, isorhamnetin,
kaempferol, quercetin.
Antihaemorrhagic.
21 Sage
5-methoxysalvigenin, camasol,
1, 8-cineole, linalyl acetate.
Carminative; antispasmodic;
antiseptic; astringent.
22 Senega Hydroxycinnamin acid,
arabinose, melibiose,
1,5anhydro-D glucitol.
Expectorant, diaphoretic;
emetic.
23 Tensy β- sitosterol, campesterol,
taraxasterol, ά-amyrin.
Anthelmintic, carminative,
Antispasmodic.
24
Embelica officinalis
Vitamine, phyllemblin tannins.
Diuretic Laxative.
25 Curry tree murraya
koenigir Pyroanocarbazole type aldaloid
myrrayacine Girinimbine
Antidiarrhocal antioxidant.
26 Blueberry leave Caffeoylquinic 3,5
dicafeylqunic neo chloroqnic
4 caffcoyl quinic
3coumaroulqunic Chloroqenic
Acid.
Diabetes.
27 Steviarebaudiana Hydrocarbons & Diterpenes,
glucosides Stevioside,
Rebaudioside Dulcoside,
Rebaudioside.
Diabete&Herbal supplement.
28 Cinnamon Zeylanicum
Eugenol, Cinnamaldehyde
Phellandrene, Pinene
Cymene, Caryolonyllenq.
Carminative Stomachic
Astringent Antiseptic.
29
Feniculam Valgare Fenchone, Anethole
Phellandrene Lemonene
Carminative Expectorant
Flavauring Agent.
30 Capparis deciduas Isothiocynate, Glucoside
Glucocapparin, n-Pentacsane n-
tricontanol
Dietary supplement.
31
Bhumi Amla
Phyllanthus Amarus
Lignans-a diarulbutane
Phyllanthin Hypophyllanthin
Amariin, Amarulone.
Diuretic Antiviral Anticancer
Hepatoprotective.

37
NMTGCOP
32 Ailanthus excelsa Phytol, linolenic Acid
Flavonoids, Saponins
Saponins, Protein
Quassinoids, terpenoids
Cumarins.
Antifungal Antileukemic.
35
Centellqasiatlica
Asiaticoside madecassoside. Leprosy nervine tonic
Sedative skin disease.
36 Withaniasomnifera Withanine, somniferine
somnine, withananine
tropine, Ansferine Di-
Isopelletierine withaferin,
withaferine-A withanolide D.
Sedative, Hypnotics
Respiratory Stimulant
Fmmunomodulatory.
37
Picrorrhiza Krroa Picroside-I , Picroside-II ,
kutkiside.
Bittertonic Antiperiodic
Febifuge stomachic.
38 Aeglemarmelos corr. Marimelosin Furocumarin Digestive Antidiarrhoreal.
39 Trigonellafoenumgraecum Protein, starch. B carolene,
gum Lipid, Ca, p, Fe, Zn, Mn,
“Trigonelline” Sesquiterpene.
Carminative Diabetes Heart
disease Aphrodisiac.
40
Momordica charantia
Triterpenoid, Saponins
Charantin, momordicin.
Hypoglucemic.
41 Azadirachta Indica
Azadirachtin Meliantriol
Nimbin, Nimbidin, Myricitin.
Insecticide Nematicide
Mematicide Antimicrobial
Spermicidal.
42 Commiphoramyrrha Sesquiterpenes & Acid a
pinene, cadinene Limonene,
Eugenol, Cuminaldhyde
Acetic Acid, m-cresol.
Wound Healing
Antibacteral Antiseptic,
Respiratory disease.
43 Evolvulus alsinoides Shankhpushpine Volatile oil Braintonic Sedative.
44 Embeliaribes Embelin known as z, s
Dihydroxy-3 undecyl-l,4 –
benzoquinone
Antioxidant Antimicrobial
Anthelmintic oral
contraceptive.

38
NMTGCOP
45 Mesuaferrea linn Betulinic Acid. 1,8
dinydroxy-3methoxy6-
methul anthraquinone,
Hydrocarbons, Carboxylic
Acid.
Antibiotic Astringent
Stomachic Expectorent
Dysentry.
46 Sweritachirayata
(Gentianaceae)
Gentiopcrin Stomachic Antiphretic.
47 Terminalia bellerica Gallic Acid, Chebulogic Acid Astringent.
48
Terminaliachebula Chebulic Acid chebulogic
Acid gallic acid.
Astringent Stomachic
Purgative.
49 Acacia-or
Acaciaarabica
Arabin oxidase Emulsifying suspending
Microenapsulation.
50 Shilajeet Herboiminerals Generaltonic Aphrodisiac.
51 Pterocarpus Marsupinum Kinotannic Acid kinored
KPyrocotechin (Catechol)
Resin, gallicacid.
Astrigent Diarrhoea
Dysentry Hypeoglycemic.
52
Andrographis- Paniculat
Androgrpholide Bitter tonic Anthelmentic
Hepatoprotective.
53 Ailiumsativum Carbohudrate, Proteins
Fat, Phosphorus
Potassium, Calcium
Allin.
Antioxidant
Hypatoprotective Amoebic
Dyusentery.
54 Syzygium CuminiLinn Flavonoides, Oleanolic Acid,
triterpenoides 3,4,5
tetrahydroxy Cyclo nexane-
Carboxalic Acid, 3 (3,4
Dihydroxy Cinnamate 10-
glycoside.
Bronchiti’s Blood Purifier
Diabetes.
55 (Bhilwa) or Semicarpus
anacardium
Biflavonoides, Phenolic
bhilawanols, minerals
Vitamins, Amino Acid
Anacardosidc.
Antilnflammatory
Anticancer
meuroprotective.

39
NMTGCOP
56 Tinospora cardifolia
Allcaloids, diterpenoid
Lactones Glycoside, steroids
Sesquiterpenoid, Phenolics
Aliphatic comp.
Polysaceharides.
Diuretic, Bittertonic,
Aphrodisiac.
57 (Punarnava) or
Boehavia diffusa
Punarnavine Punernavoside. Diuretic stomachic
Jaundice Tretment.
58 Terminelia Arjuna E- llagic Acid B-sitosterol. Cardiotonic Hypotenisve.
59 Bombax cieba Lupeol, a sitosterol
sesquiterpenes Flovonoid
Alkaloids, steroids Caleium
& Napthaquinones.
Antidiabetics Antiinflanna
to ry Analgesic
Antioxidant.
Table 3: Marketed preparation having antidiabetic activity.
S.No Brand name Ingredient used Mfd.by
1 Glucolev
Amaalaki powder, sudha shilagit;
jasad bhasma; methika; beej;
madhunasimi; ashwagandha.
Bajaj herbal
2 Madhumehari
granules Gudmar; jamun guthly; gulvel; karela
beej; khadir chuma; haldi; amla; vijay
sar; tejpatra; shilajit; gulalphal chuma;
kutki; chitrak;
Baidynath.
methi; neem patti; bilva patra; trivang
bhasma.
3 Diabegon
Harad; behead; amala; shunthi; pipali;
kali mirch; gudmar patra; jamun beej;
shudha shilajit; vasant kusma rus;
lauha bhasma; trivang bhasma; svama
makshik bhasma;
Dindaal aushadhi (P)
Ltd.

40
NMTGCOP
4 Amree capsule
Tejpatra; bilvpatra; vijay sar,
gulalpatr; jamun patra; methi beej;
gudmar patra; neempatra; giloe;
trivang bhasma; sudhshilajeet.
Aimil pharmaceutical
Ltd.
5 Diabecon
Meshshringi; pitasara; yashtimadhu;
apatarangi; jambu; shatavari;
punamava; mundatika; gudachi;
gugul; shilajit; kairla;gokshura;
bhumiamalki; gumbhari, karpari;
triphala.
Himalaya Aurvedic
pharmaceutical.
6
Madhumehari yog
(capsule)
Baidynath pharma.
7 IIogen
Glurcumalonga; strynchonos
polotarum; slalaciaop longa;
innophura cardiophuria; atevetrial
zizanioibes; etc.
Pankaj kasturi pharma.
Ltd.
8 DBT (Capsule)
Jamun beej; madhunasini; gugul;
kutki; haridhara etc.
Dabur pharmaceutical.
9 Glucomap (Tablet). Enicostemmalittorale; thylanthus
neum; ungania jamplona; azadirecta
indica; gerulvalae arjuna.etc.
Maharashuri ayurvedic.
10 Glucodap. (Tablet)
Amalaki powder; charan bhasma;
methi beej; Jamun beej; etc
Bajaj pharmaceutical.
11 Diabatreat (Syrup)
Areca, Syzygium Cumini Cannabis
Sativa Quercus in Fectoria
Momordica Charantia, Asperagus
Adscendens Azadirachta Indica
Tinospora Cardifolia Angle
Marmelos, Trigonella Foencum
Gurmar leaf Emblica officinalis.
Dhanvantri Pharma.
12 Greek-CD (Tablet) Debitterised methiseed, Soluble
fibres from vegetable orign.
Mitocon Biotec.

41
NMTGCOP
13 Gludibit Gymnema Sylvestre Vijay sar,
mamajjak Citrus Limon Sapta
chakre.
Lupin Pharma.
14 Nosulin Guargum, Tundika, methi,
Meshasring.
Dey’s.
15 Diabeta Plus Gurmar, Karela, Saptrangi,
Ashwagandha, Tulsi.
Krishna Herrbal
Company.

42
NMTGCOP
CONCLUSION
Diabetes mellitus a metabolic disease and its management have aware the clinicians in all over the
countries. In current status, a high number of populations have this disease which is related with the
modern life style, unhealthy diet and sedentary life. The management of Diabetes Mellitus for Type
I, is usually inject-able insulin delivery in contrast to Type II which the majority of drugs are orally
administered. Currently, the management of Type II diabetes focuses on glucose control via
lowering of fasting and postprandial blood glucose and hemoglobin A(1c). In the foreseeable
future, researchers believe that the replacement of subcutaneous injections of insulin with
nanocarriers could improve the quality of diabetic patients. Furthermore, reducing of blood sugar
levels with active ingredients of plants either as primary treatment or as adjunct therapy to
conventional medications is a hopeful therapy.
Diabetes mellitus is the epidemic of the century and without effective diagnostic methods at
an early stage, diabetes will continue to rise. This review focuses on the types of diabetes and
the effective diagnostic methods and criteria to be used for diagnosis of diabetes and
prediabetes. Evidently, diabetes is a complex disease with a large pool of genes that are
involved in its development. The precise identification of the genetic bases of diabetes
potentially provides an essential tool to improve diagnoses, therapy (more towards
individualized patient targeted therapy) and better effective genetic counseling. Furthermore,
our advanced knowledge of the association between medical genetics and the chronic
complications of diabetes, will provide an additional advantage to delay or eradicate these
complications that impose an immense pressure on patient’s quality of life and the
significantly rising cost of health-care services.

43
NMTGCOP
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NMTGCOP
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