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Antidiabetic Drugs
 Definition: Diabetes Mellitus
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A group of metabolic disorders characterized by

hyperglycemia associated with abnormalities in
carbohydrate, fat, and protein metabolism.
 TYPES of DM
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1. Type 1 diabetes (beta cell destruction, usually

leading to absolute insulin deficiency)
 Immune-mediated
 Idiopathic
2. Type 2 diabetes (may range from predominantly
insulin resistance with relative insulin deficiency to
a predominantly insulin secretory defect with
insulin resistance).
3. Other specific types of diabetes
4. Gestational diabetes mellitus (GDM)
 Criteria for the Diagnosis of Diabetes
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1. Symptoms of diabetes plus random blood glucose

concentration 11.1 mM (200 mg/dL) or
2. Fasting plasma glucose 7.0 mM (126 mg/dL) or
3. Two-hour plasma glucose 11.1 mM (200 mg/dL)
during an oral glucose tolerance test.
4. HbA1c 6.5%___ The rate of formation of HbA1c is
proportional to the average blood glucose concentration
over the previous 3 months
 Non-pharmacologic
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therapy

I. Diet: Medical nutrition therapy (MNT)

 Is recommended for all persons with DM and along
with activity, is a cornerstone of treatment.
 Type 1 DM, the focus is on regulating insulin
administration with a balanced diet to achieve and
maintain a healthy body weight.
 Type 2 DM often require caloric restriction to promote
weight loss, and portion size and frequency are often
issues
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II. Physical Activity:

Aerobic exercise improves
 Insulin sensitivity and glycemic control in the majority
of individuals
 Reduces cardiovascular risk factors,

 contributes to weight loss or maintenance, improves

well-being.
 Drugs for the Treatment
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of DM

1. Insulin
2. Oral hypoglycemic agents
 Insulin
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Actions of insulin
 Anabolic effect
 Promoting the uptake, use, and storage of the major
nutrients
 Stimulate glucose uptake by tissues.

 Decrease glycogenolysis and increase glycogenesis

 Decrease gluconeogenesis

 Inhibit lipolysis and promote lipogenesis

 Promote transport of amino acids into cells

(promotes protein synthesis).
 Insulin
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Insulin Preparation
Insulin is a small protein which contains 51 amino
acids
Most preparations are supplied at neutral pH,
Doses and concentration of clinically used insulin
preparations are expressed in international units
time-action profiles of insulin preparations
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Administration
 Because insulin is a protein, it is degraded in the
GIT if taken orally.
 It is generally administered parenterally usually
SC, but IV in hyperglycemic emergency.
Goal of insulin administration ……. to mimic
Basal insulin secretion
• Overnight, Fasting, Between meals
Prandial _ insulin release after food or meal
 Regular insulin (Humulin R, Novolin R)

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– Should be injected 30-45 minutes before a meal.

– It is usually given Sc or IV (in emergency situations)
– Also given intramuscularly.
– It is the only insulin preparation suitable for IV
administration.
 Short-Acting Insulin Analogues
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– Insulin Lispro, Aspart, Glulisine

– Absorbed more rapidly from subcutaneous sites than
regular insulin
– have lower rates of hypoglycemia
Should be injected 15 min or less before a meal.
 Neutral protamine hagedorn (NPH)

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NPH insulin is usually given either once a day (at

bedtime) or twice a day in combination with short-
acting insulin.
Should only be given subcutaneously (never IV)
 Insulin glargine (LANTUS)
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It is a clear solution with a pH of 4.0

When injected into the neutral pH of the subcutaneous
space, aggregations occurs, __ resulting in prolonged
(once daily administration), but predictable, absorption
from the injection site.
It cannot be mixed with short-acting insulin
preparations that are formulated at a neutral pH due to
it's acidic pH.
 Side effects of Insulin
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Hypoglycemia
 main undesirable effect
Rapid development of hypoglycemia causes signs of
autonomic hyperactivity— both sympathetic
(tachycardia, palpitations, sweating, tremulousness) and
parasympathetic (nausea, hunger)—and may progress to
convulsions and coma if untreated
Treatment of hypoglycemia is to take a sweat
drink or snack or if the patient is unconscious IV
glucose (40% solution) or IM glucagon
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 Allergic reactions
 lipodystrophy at injection site i.e. fat
accumulation may occur at the site of injection
 Hypokalemia
 Weight gain
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Oral Hypoglycemic Agents

 Oral Hypoglycemic Agents
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Includes
1. Insulin secretagogues
a) sulfonylureas,
b) meglitinides
2. Biguanides,
3. Thiazolidinediones,
4. α-glucosidase inhibitors,
Sulfonylureas
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Properties of Insulin Secretagogues
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 Sulfonylureas (SU)
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Mechanism of Action SU
– Stimulate insulin release from the pancrease
– Reduction of Serum glucagon concentrations
 The 1st GC sulfonylureas:
– Now rarely used in the treatment of type 2 diabetes.
– Tolbutamide _ short acting
– Chlorpropamide _ long acting
 Second-Generation Sulfonylureas
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___ glyburide, glipizide, and glimepiride___

 Prescribed more frequently than the first-generation
agents because they have fewer adverse effects and drug
interactions.
 Adverse Effects of SU
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 Hypoglycemic reactions, including coma__ This is a

particular concern in elderly patients
 Weight gain
 Less frequent side effects
 Nausea and vomiting, cholestatic jaundice, Blood
dyscrasias__ agranulocytosis, aplastic and hemolytic
anemias, generalized hypersensitivity reactions, and
dermatological reactions
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Contraindications
 Type 1 diabetes
 Pregnancy and lactation, and,

 For the older preparations, significant hepatic or renal

insufficiency.
 Meglitinide__
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Mechanism of action___ Bind to the same KATP Channel as

do Sulfonylureas, to cause insulin release from β-cells.
Repaglinide
– Taken orally, fast onset of action( Peak approx. 1hr )__
allow for multiple preprandial use__ indicated for use
in controlling postprandial glucose
Nateglinide
 The latest insulin secretagogue
 Promotes a more rapid secretion of insulin than other
available oral antidiabetic agents
 Biguanides __ Metformin
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Mechanism of Action of metformin

Increased glycogen storage in skeletal muscle,
 Increased insulin sensitivity, and
 Lower rates of hepatic glucose production,

 Lower blood glucose levels.

NOTE: Metformin is less fasting hyperglycemia as well
as lower postprandial hyperglycemia “euglycemic”
agents.
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Advantages of Metformin over SUs

 Does not cause hypoglycemia.
 Does not result in weight gain.
 (mean weight loss of 1.2 kg compared with 1.7 kg
increase with sulfonylurea or insulin therapy)
 superior or equivalent efficacy of glucose lowering
 Lower rates of cardiovascular disease and mortality
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Adverse Effects
 Gastrointestinal complaints
 Vitamin B12 deficiency (prolonged use)- 20-30%
 Lactic acidosis- rare but risk increases in conditions like
– Which decrease tissue perfusion_ such as sepsis,
myocardial infarction, and congestive heart failure
– Decrease clearance _ renal failure
 Thiazolidinediones (TZDs)
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Two TZDs are currently available to treat patients with

type 2 diabetes_ rosiglitazone?? and pioglitazone.
Mechanism of Action
 Resulting in increased insulin sensitivity in adipose
tissue, liver, and skeletal muscle
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Adverse Effects
– Mild to moderate edema
– Weight gain
– Hepatotoxicity ?
– Can increase the risk of bone fracture in women
– Both drugs increase the risk of heart failure __ not be
used in patients with moderate to severe heart failure,
and they should be discontinued in those who develop
clinically apparent heart failure while being treated
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The end