MANAGEMENT OF TYPE 2 DIABETES MELLITUS

Rakshita Jain
Batch 2017
Department of Pharmacology
Shri Lal Bhadur Shashtri Goverment Medical College
 ABSTRACT
Diabetes is highly prevalent and serious chronic debilitating disease and reported to
be the fourth main cause of death in Europe. Globally, an estimated 422 million adults
are living with diabetes (2016 data from the World Health Organization) Diabetes
prevalence is increasing rapidly; previous 2013(estimates from the International
Diabetes Federation )put the number at 381 million people having diabetes. In India ,
diabetes is fast gaining the status of potential epidemic with more than 62 million
diabetic individuals currently diagnosed with the disease. Type 2 diabetes makes up
about 85-90% of all cases. The number is projected to almost double by 2030.
Increases in the overall diabetes prevalence rates largely reflect an increase in risk
factors for type 2, notably greater longevity and being overweight or obese. Despite
extensive evidence of benefits of tight glycemic control, large proportions (>60%) of
people with diabetes do not achieve target glycemic control. Although prevention and
treatment of diabetes and its complications play a key role in reducing its morbidity
and mortality, they require an integrated team approach at national and international
levels. The key issues in the management of people with T2DM include early
detection of problems, realistic goal setting, improved patient adherence, better
knowledge and understanding of pharmacotherapeutic treatment options and prompt
intervention. Thus, eeducation of the health care team on the management of diabetes and
on how to educate people with diabetes is one major aspect that requires strengthening.

Keywords: T2DM, integrated, management

 INTRODUCTION
Diabetes is a serious, chronic metabolic disorder that occurs either when the pancreas
does not produce enough insulin or when the body cannot effectively use the insulin it
produces . Raised blood glucose, a common effect of uncontrolled diabetes, may, over
time, lead to serious damage to the heart, blood vessels, eyes, kidneys and nerves.
Type 2 diabetes include 85-90% of all cases of diabetes. Others include type 1(Insulin
Dependent Diabetes Mellitus), type 3 ( secondary causes of hyperglycaemia), type 4
( Gestational Diabetes Mellitus)
Type 2 diabetes (formerly called non-insulin-dependent or adult-onset diabetes)
results from the body’s ineffective use of insulin. Symptoms include excessive
urination and thirst, constant hunger, weight loss, vision changes and fatigue, but are
often less marked or absent. As a result, the disease may go undiagnosed for several
years, until complications have already arisen. For many years type 2 diabetes was
seen only in adults but it has begun to occur in children.
The risk of type 2 diabetes is determined by an interplay of genetic and metabolic
factors. Ethnicity, family history of diabetes, and previous gestational diabetes
combine with older age, overweight and obesity, unhealthy diet, physical inactivity
and smoking to increase risk.
Excess body fat, a summary measure of several aspects of diet and physical activity,
is the strongest risk factor for type 2 diabetes, both in terms of clearest evidence base
and largest relative risk. Overweight and obesity, together with physical inactivity, are
estimated to cause a large proportion of the global diabetes burden. Higher waist
circumference and higher body mass index (BMI) are associated with increased risk
of type 2 diabetes, though the relationship may vary in different populations.
Populations in South-East Asia, for example, develop diabetes at a lower level of BMI
than populations of European origin .
Several dietary practices are linked to unhealthy body weight and/or type 2 diabetes
risk, including high intake of saturated fatty acids, high total fat intake and inadequate
consumption of dietary fibre. High intake of sugar-sweetened beverages, which
contain considerable amounts of free sugars, 1 increases the likelihood of being
overweight or obese, particularly among children. Recent evidence further suggests an
association between high consumption of sugar-sweetened beverages and increased
risk of type 2 diabetes .
Early childhood nutrition affects the risk of type 2 diabetes later in life. Factors that
appear to increase risk include poor fetal growth, low birth weight (particularly if
followed by rapid postnatal catch-up growth) and high birth weight .
Active (as distinct from passive) smoking increases the risk of type 2 diabetes, with
the highest risk among heavy smokers . Risk remains elevated for 10 years after
smoking cessation, falling more quickly for lighter smokers
Various complications often develop as a consequence of the metabolic derangements
in DM (type-1 and type-2) over many years (particularly if there is poor glycaemic
control). As a result there may be microvascttlar complications e. g.,retinopathy,
nephropathy and neuropathy) as well as macrovascular complications such as
atherosclerosis and diabetic dyslipidaemia (elevated TGs and LDL). Diabetic
neuropathy results due to demyelination of axons. Diabetic retinopathy and
nephropathy result due to accumulation of sorbitol produced by glucose reduction by
aldose reductase. Sorbitol causes thickening of the basement membrane of capillary
endothelium, which leads to the narrowing of the microvessels and deficiency in as
tissue perfusion. A major complication of diabetes is the formation of cataract
because excess glucose gets deposited on lens to make it cloudy.
Diabetes imposes a large economic burden on the global health-care system and
the wider global economy. Based on cost estimates from a recent systematic
review, it has been estimated that the direct annual cost of diabetes to the world is
more than US$ 827 billion The increase in total global diabetes health expenditure
is expected to continue. Low- and middle- income countries will carry a larger
proportion of this future global health-care expenditure burden than high-income
countries.
 LITERATURE REVIEW
Management of type 2 Diabetes Mellitus
BASIC PRINCIPLES
1. Correct diagnosis- using appropriate diagnostic criteria.
2. Treatment-not only considering lowering blood glucose levels but also co-
morbidities correction of any associated CVD risk factors such as smoking,
hyperlipidemias, and obesity as well as monitoring of blood pressure and treatment of
hypertension.
3. Education of the person with diabetes and his/her family
4. Self-monitoring
5. Access to the basic requirements essential to practise self-care.
6. Record keeping
7. Individually targeted therapy

DIAGNOSIS
The diagnosis of diabetes carries considerable consequences and should therefore be
made with confidence. If the patient has classical symptoms (such as increased thirst
and urine volume, unexplained weight loss, pruritus vulvae or balanitis) or drowsiness
or coma, associated with marked glycosuria, the diagnosis can be readily established
by demonstrating fasting hyperglycaemia. If the fasting blood glucose concentration
is in the diagnostic range shown in Table , an oral glucose tolerance test (OGTT) is
not required. An OGTT is performed if the diagnosis is uncertain and the blood
glucose values are in the equivocal range. It is often sufficient to measure the blood
glucose values only after fasting and 2 hours after a 75 g oral (anhydrous) glucose
CLASSIFICATION
Once the diagnosis is confirmed, an attempt should be made to classify the type of
diabetes. Distinction between the two major types of diabetes can be difficult.
However, the following generally favour the diagnosis of insulin-dependent diabetes
mellitus:
[Link] onset onset at young age (20 years and younger)
2. rapid weight loss
[Link].
Factors favouring a diagnosis of non-insulin-dependent diabetes mellitus:
1. absence of classical symptoms of diabetes
2. older age of onset (over 30 years)
3. presence of obesity.
Maturity onset diabetes of youth (MODY) is a rare type of diabetes that may be
inherited as an autosomal dominant condition. It is characterized by onset at young
age and correction of hyperglycaemia without insulin.

INITIAL ASSESSMENT

A standardized form should be used for recording clinical data and the results of
investigations. Record-keeping is important to ensure good quality of care and is
essential for follow-up and monitoring. Clinical assessment on presentation should be
performed by a physician in all cases.
A full history is needed. In addition to the presenting symptoms, emphasis should be
placed on:
1. risk factors of cardiovascular diseases, such as smoking, hypertension, obesity,
hyperlipidaemia and family history
2. symptoms of cardiovascular complications including angina, heart failure and
claudication
3. visual symptoms
4. symptoms of neuropathic complications such as numbness, pain, muscle
weakness, gastrointestinal symptoms including diarrhoea, impotence and
bladder dysfunction
5. drug history
6. past history
7. gestational history.
A complete examination is part of the minimum requirements. Certain aspects of the
physical examination should receive special attention. These include:
1. height and weight measurements
2. blood pressure (lying and standing positions to detect postural change)
3. cardiovascular examination for abnormal signs and assessment of peripheral
pulses
4. examination of the lower limbs for peripheral pulses, sensation, ankle jerk and
foot lesions
5. ophthalmoscopy with dilated pupils.
Laboratory assessment should include:
1. a blood glucose measurement as a minimum requirement to confirm the
diagnosis
2. urine examination for ketones, protein and glucose serum creatinine
measurement in all hypertensive patients and those with proteinuria
3. electrocardiography and measurement of total serum cholesterol and
triglycerides in high-risk individuals
4. HBAIC measurement and quantitative measurement of urine protein as
optional investigations that may be performed as part of the initial assessment
where facilities and resources allow

TREATMENT
The major components of the treatment of diabetes are: 1. diet (combined with
exercise if possible) 2. oral hypoglycaemic therapy 3. insulin treatment
Education of the person with diabetes is an essential component of management in
every case

Dietary treatment Diet is a basic part of management in every case. Treatment

cannot be effective unless adequate attention is given to ensuring appropriate
nutrition. Dietary treatment should aim at:
1. ensuring weight control
2. providing nutritional requirements
3. allowing good glycaemic control with blood glucose levels as close to normal
as possible
4. correcting any associated blood lipid abnormalities ensuring consistency and
compatibility with other forms of treatment if used, for example oral agents or
insulin.
The following principles are recommended as dietary guidelines for people with
diabetes:
1. Dietary fat should provide 25-35% of total intake of calories but saturated fat
intake should not exceed 10% of total energy. Cholesterol consumption
should be restricted and limited to 300 mg or less daily.
2. Protein intake can range between 10-15% total energy (0.8-1 g/kg of
desirable body weight). Requirements increase for children and during
pregnancy. Protein should be derived from both animal and vegetable sources.
 3. Carbohydrates provide 50-60% of total caloric content of the diet. Although it
has been traditionally recommended that carbohydrates should be complex
and high in fibre, more emphasis should be placed on the total amount of
carbohydrates consumed than the source of carbohydrate.
4. Excessive salt intake is to be avoided. It should be particularly restricted in
people with hypertension and those with nephropathy.
5. Artificial sweeteners are to be used in moderation. Nutritive sweeteners
(sorbital and fructose) should be restricted.
6. The same precautions regarding alcohol intake that apply to the nondiabetic
population also apply to people with diabetes. Additionally, however, alcohol
tends to increase the risk of hypoglycemia in those taking antidiabetic drugs
and should be particularly avoided in those with lipid abnormalities and
patients with neuropathy.
7. Except in special conditions like pregnancy and lactation, routine vitamin and
mineral supplementation is generally not needed in people with a well
balanced diet. There is, at present, no definite evidence to confirm that such
treatment has any benefits.
8.
Exercise Physical activity promotes weight reduction and improves insulin
sensitivity, thus lowering blood glucose levels. Together with dietary treatment, a
programme of regular physical activity and exercise should be considered for each
person. Such a programme must be tailored to the individual’s health status and
fitness. People should, however, be educated about the potential risk of
hypoglycaemia and how to avoid it.

Oral agents

Metformin
Metformin is considered the agent of first line for treatment of T2DM, in the absence
of contraindications.
MECHANISM OF ACTION Biguanides do notcause insulin release, but presence of
insulin is essential for their action. Activation of AMPdependent protein kinase
(AMPK) plays a crucial role in mediating the actions of metformin, the key features
of which are:
1. Suppresses hepatic gluconeogenesis and glucose output from liver. This is the
major action responsible for lowering of blood glucose in diabetics.
2. Enhances insulin-mediated glucose uptake and disposal in skeletal muscle and fat.
3. Interferes with mitochondrial respiratory chain and promotes peripheral glucose
utilization through anaerobic glycolysis.
PHARMACOKINETICS Clearance of metformin approximates g.f.r. It accumulates
in renal failure and increases the risk of lactic acidosis.
ADVANTAGES
• nonhypoglycaemic
• weight loss promoting
• has potential to prevent macrovascular as well as microvascular complications of
diabetes
• no acceleration of β cell exhaustion/ failure in type 2 DM.
• antihyperglycaemic efficacy (HbA1c reduction by 0.8–1.2%) equivalent to other
oral drugs.
• can be combined with any other oral or injectable antidiabetic, if one drug is not
adequate.
CONTRAINDICATIONS Metformin is contraindicated in patients with factors that
predispose to lactic acidosis. The predisposing factors are: A renal function damaged,
concomitant liver disease or excessive alcohol intake, unstable or acute heart failure
and personal history of lactic acidosis.
SIDE EFFECTS The most frequents are gastrointestinal, such as anorexia, nausea,
abdominal discomfort and diarrhoea; they are usually mild and transient. Also,
metformin reduces intestinal absorption of vitamin B12. Less common is lactic
acidosis
DOSAGE 0.5 -2.5g 0nce or twice daily

Insulin secretagogues: Sulfonylureas and meglitinides

Sulfonylureas and meglitinides or glinides (insulin secretagogues) are two different

classes of oral hypoglycaemic drugs but they have a common mechanism of action,
and both stimulate pancreatic beta cells to release [Link] are a classic
first or second-line therapy for patients with T2DM, and since their introduction to
clinical practice in the 1950s they have been widely [Link] stimulate
insulin release through similar mechanisms but they have a different subunit binding
site, with a more rapid absorption and more rapid stimulus to insulin secretion.
However they require more frequent dosing.
MECHANISM OF ACTION: Both sulfonylureas and glinides base their mechanism
of action in increasing insulin secretion, which is regulated by ATP-sensitive
potassium channels (KATP potassium channel) located in the membrane of pancreatic
beta cells[74]. Although the receptor’s binding site is different for sulfonylureas and
glinides, they both induce channel closure and cell depolarization leading to an
increase in cytoplasmic calcium level and consequently insulin secretion[37].
PHARMACOKINETICS: Differences in pharmacokinetic and binding properties of
insulin secretagogues result in the specific responses that each drug produces.
Sulfonylureas can be divided into first- and second-generation agents. Glyburide
(known as glibenclamide in Europe), glipizide, gliclazide and glimepiride are second-
generation sulfonylureas. New generation agents are more potent and have fewer
adverse effects. Although second-generation sulfonylureas are equally effective, there
are differences in absorption, metabolism, and duration of action as well as in
effective dose; for example, glyburide has active metabolites that can prolong his
action. There are two different glinides: Repaglinide and nateglinide. Repaglinide is a
member of the meglitinide family different from the sulfonylurea. Nateglinide is a
derivate of phenylalanine and it is structurally difference from sulfonylureas and
meglitinide. They both cause less hypoglycaemia and less weight gain due to their
shorter half-life and a different sulfonylureas receptor binding site, leading to faster
absorption and a more rapid stimulus to insulin secretion
ADVANTAGES AND EFFECTIVENESS:Sulfonylureas and meglitinides can be
effective when employed as monotherapy, or in combination with other oral
hypoglycaemic drugs or insulin. Sulfonylureas are the most cost-effective glucose-
lowering agents, have been on the market for a long time, and are widely utilized
because of their long term efficacy and safety history, low cost and extensive clinical
trial data demonstrating good glucose-lowering efficacy. The glucose-lowering
effectiveness is said to be high for sulfonylureas (expected HbA1c reduction 1.0%-
1.5%) and generally lower for meglitinides (0.5%-1.0%)[9,57].
SIDE EFFECTS: Loss of efficacy, hypoglycaemia and weight gain represent the main
problems related to the use of these drugs.
DOSAGE glibenclamide 0.5 to 3g twice or thrice daily
Glimepride 1-6mg once or twice daily
Repaglinide 1-8 mg thrice daily

Alpha-glucosidase inhibitors
There are three currently available agents, acarbose, miglitol and voglibose. These are
mild anti hyperglycaemics, mostly used as supplementary drugs to a hypoglycaemic
regime.
MECHANISM OF ACTION: Alpha-glucosidases inhibitors are structurally similar to
natural oligosaccharides with higher affinity for alpha-glucosidases, and they produce
a reversible inhibition of membrane-bound intestinal alpha-glucoside hydrolase
enzymes. This cause delayed carbohydrate absorption and digestion, and results in a
reduction in postprandial hyperglycaemia. Because reduced blood glucose
concentrations, alpha-glucosidase inhibitors do not enhance insulin secretion.
SIDE EFFECTS: The side effects are mainly gastrointestinal and include flatulence,
diarrhoea and abdominal pain.
DOSAGE 50-100mg TDS at the beginning of each major meal

Thiazolidinediones

Two TZD are currently available in United States: Rosiglitazone and pioglitazone. In
Europe, since 2010, rosiglitazone was suspended by the European Medicines Agency,
based on the overall risks of rosiglitazone exceed their benefits. It is also banned in
India .
MECHANISM OF ACTION: TZD increase insulin sensitivity by acting on muscle,
adipose tissue and liver to increase glucose utilization and decrease glucose
production. TZD bind to peroxisome proliferator-activated receptors (PPARs).
Side effects plasma volume expansion, edema, weight gain, headache, myalgia and
mild anaemia.. Few cases of hepatic dysfunction have been reported; CHF may be
precipitated or worsened. Glitazones increase the risk of fractures, especially in
elderly women.
DOSAGE 15-45 mg once daily

Dipeptidyl peptidase-4 inhibitors

The incretin agents (GLP1 and GIP), secreted by intestine L cells, increase insulin
secretion and inhibit glucagon in response to nutrient inputs. The glucoregulatory
effects of incretins are the basis for treatment with inhibitors of DPP4 in patients with
T2DM. Agents that inhibit DPP4, an enzyme that rapidly inactivates incretins,
increase active levels of these hormones and, in doing so, improve islet function and
glycaemic control in T2DM.
iDPP4 are used as monotherapy in patients inadequately controlled by diet and
exercise, and dual therapy in combination with metformin, TZDs and insulin. iDPP4
are well tolerated; they have a low risk of producing hypoglycaemia, and maintain the
patient’s weight. There are five iDPP: Sitagliptin, Vildagliptin, Saxagliptin,
Linagliptin and Alogliptin.
SIDE EFFECTS: headache, nasopharyngitis, and upper respiratory tract infection
INDICATION Insulin release is glucose dependent; therefore not likely to induce
hypoglycaemia.
• Suppress glucagon release, thus lowering fasting blood glucose as well.
• Improve cell health and retard progression of cell failure.
• Body weight neutral.
• Mostly single daily dose, well tolerated with few side effects, no serious toxicity, no
drug interactions, except with saxagliptin.
However, they are new drugs and have not withstood the test of time yet. Their
impact on cardiovascular mortality and other outcomes is yet to be measured. As
such, most professional guidelines place them as second line/add on antidiabetic
drugs. They are especially valuable for patients having body weight problem and
those experiencing frequent episodes of hypoglycaemia.
DOSAGE sitagliptin 100 mg once daily
Vildagliptin 50 mg twice daily

Sodium glucose co-transporter-2 inhibitor

MECHANISM OF ACTION iSGLT2 inhibit renal reabsorption of glucose, increase
its excretion and reduce hyperglycaemia in patients with T2DM. Therefore, reducing
the reabsorption of glucose by inhibition of SGLT2 is a new way to treat T2DM. The
increase in glucosuria and diuresis produced results in a reduction in weight and blood
pressure.
Kidneys from healthy people filter approximately 180 g of glucose each day through
renal glomerulus and reabsorbed in the then proximal convoluted tubule. There are
two types of SGLT; SGLT1 located mainly in the small intestine and the kidney
proximal convoluted tubule, and SGLT2 located only in the proximal tubule (segment
1 and 2), that are responsible for about 90% of glucose reabsorption. SGLT2
inhibitors block the SGLT2 transporter in the proximal tubule, to lower glucose
reabsorption and increase its excretion in the urine. Glucose is excreted in the urine
and plasma levels are reduced by improving glycaemia figures plasma.
ADVANTAGES It is an independent mechanism of insulin, there is low risk for
hypoglycaemia, and no risk of fatigue or overstimulation of the beta cells.
DRUGS The three most representative drugs family iSGLT2 are: Dapagliflozin,
canagliflozin and empagliflozin.

Insulin

In people with NIDDM, insulin is indicated in the following situations :

— when diet and oral hypoglycaemic drugs fail to control hyperglycaemia and
achieve therapy targets;
— diabetes during pregnancy when diet alone is inadequate;
— when oral hypoglycaemic drugs are contraindicated;
— during stressful conditions such as infection and surgery.
PREPERATION AND PHARMOLINETICS: Long-acting insulins (glargine and
detemir), ultra-long-acting insulins (degludec and Glargine U-300) and rapid-acting
insulins (aspart, lispro or glulisine) are available.
Insulin glargine and human insulin are the same except for a substitution of glycine
for asparagine in position A21 and by the addition of two arginine molecules in the B-
chain of the insulin molecule. These modifications originate a change in the pH such
that, after administration, glargine precipitates in the subcutaneous tissue making
hexamers, which delays absorption and extends duration of action. Glargine has a
duration of action that usually lasts 24 h. Glargine cannot be mixed with rapid-acting
insulins as the kinetics of both the rapid acting insulin and glargine and will be
modified.
Insulin detemir is another insulin analog developed by removing a threonine an
acylating a lysine with 14-carbon fatty acid; the fatty acid side chain allows albumin
binding and results in prolongation of action. Detemir cannot be mixed with rapid-
acting insulins.
When glargine and detemir are administered in high doses, both show a peak on
pharmacokinetic and pharmacodynamics profile. Insulin degludec is a modified B
chain analogue that forms hexamers and di-hexamers when is administrated.
Compared with other long-acting insulins (glargine and detemir), the insulin degludec
profile is flatter with a half life greater than 25 h, and action that exceeds 42 h, which
results in a reduction of confirmed and nocturnal hypoglycaemias. Glargine U300 is
the same glargine molecule concentrated three times; so it has the same mechanism to
slow its absorption as insulin glargine.
MECHAMISM OF ACTION insulin stimulates glucose transport across cell
membrane by ATP dependent translocation of GLUT4 to the plasma membrane
SIDE EFFETS Hyoglycaemia, local reaction, allergy and edema
REGIME 1. Split mixed regime
2. basal bolus regime
MONITORING GLYCAEMIC CONTROL

Glycaemic control should always be monitored. The absence of symptoms alone

should not be taken as an indicator of good control.
• Self-monitoring should be encouraged.
• Methods and frequency of monitoring depend on the type of treatment, the local
facilities available, and therapy targets set.
• Methods include:
— urine glucose testing;
— blood glucose measurements;
— others tests like glycated haemoglobin (HbA1c) or fructosamine measurement;
— urine ketones should also be tested during intercurrent illnesses and periods of
poor control.

DIABETES AND OTHER ILLNESSES

Metabolic control may deteriorate during infections, stressful conditions and other
intercurrent illnesses. Both the health care team and the person with diabetes should
take note of this fact and take action to avoid complications.
Actions to be taken:
• More frequent monitoring of urine and blood glucose
• Monitoring of urinary ketones
• Recognition of symptoms and signs of ketoacidosis (vomiting and other
gastrointestinal symptoms, dehydration, etc.) and early referral to a specialist.
HYPOGLYCAEMIA

Hypoglycaemia is a common complication of drug treatment and is a particular risk in

insulin-treated patients. Severe episodes can lead to serious complications and may be
potentially fatal if left untreated.
Hypoglycaemia is likely to occur under the following circumstances:
— omission of meals or inadequate food intake
— with unaccustomed physical exercise
— overtreatment with insulin or sulphonylureas
— ingestion of alcohol particularly without food
— diminishing insulin requirements due to impaired renal function.
TREATMENT OF HYPOGLYCAECMIA
• Hypoglycaemia is a medical emergency and should always be treated promptly.
• Blood glucose should be measured, using glucose-sensitive reagent strips to confirm
the diagnosis in suspected cases. But if this measurement is not immediately
available,treat as hypoglycaemia.
• In mild cases, the person with diabetes should be instructed to deal with such
episodes by having a rapidly absorbable carbohydrate or sweetened drink which may
have to be repeated as necessary.
• If the patient is confused and uncooperative or unconscious, give 10-20 grams of
20% or 50% glucose intravenously.
• When intravenous therapy is not available or possible, give glucagon, 1 mg,
intramuscularly or subcutaneously.
• Hypoglycaemia due to sulphonylureas and long-acting insulins may be prolonged.
•Therefore it is important that frequent measurements of blood glucose are made to
assess the effectiveness of therapy and to safeguard against recurrence of
hypoglycaemia.

CONCLUSION
As the prevalence and numbers of people with diabetes continue to rise – a result of
changes in the way people eat, move and live, and an ageing global population – the
already-large health and economic impacts of diabetes will grow.
These impacts can be reduced through effective actions. With sufficient lifelong
management and regular follow-up, people with all types of diabetes can live longer
and healthier lives. The occurrence of type 2 diabetes can be reduced through
population-based and individual prevention measures that target key risk factors.
While lifestyle modifications and metformin are the cornerstone of the initial
management of T2DM, there is an increasing array of second and third-line
pharmacological agents for this condition. At present there are different families of
oral and injectable drugs, available for the treatment of T2DM. These include
sulfonylureas, meglitinides, insulin, TZD and alpha-glucosidase inhibitors, and
recently with the addition of RA-GLP1 receptor agonists, iDPP4 and iSGLT2.
Moreover, insulin analogues that better simulate endogenous insulin secretion have
been developed. Metformin remains the first choice of treatment for most patients.
Other alternative or second-line treatment options should be individualized taking into
consideration patient characteristics as degree of hyperglycaemia, presence of co-
morbidities, and patient preference and ability to access treatments; and properties of
the treatment such effectiveness and durability of lowering blood glucose, risk of
hypoglycaemia, effectiveness in reducing diabetes complications, effect on body
weight, side effects and contraindications. Although it does not appear that in the near
future cure diabetes, novel safety and effective agents that will improve the quality of
life of T2DM patients, are developing
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