Antidiabetic Drugs

Clinical Pharmacist:
Dr. Rawan Al-gharaibeh
• Glucose:
 It is an energy source.
 It is stored in the body for rapid release in times of
stress.(as glycogen in the liver,, in adipose tissue as
triglyceride )

• Pancreas:
 both exocrine and an endocrine gland.
 Endocrine gland secrets insulin and glucagon
(regulation of glucose homeostasis to maintain
physiologically optimal blood glucose level, which
normally range between 70 and 100 mg/dL) .
Endogenous insulin is secreted from
cells in the pancreas

Islet of Langerhans
Alpha cell: 20%, glucagon
Beta cell: 75%, insulin
 Diabetes Mellitus

•A chronic metabolic disorder characterized by

“hyperglycemia”
•This is result due to:

 Relative or absolute deficiency of insulin

And/or insulin insensitivity(resistance).

Serious long-term complications:
 Complications of diabetes mellitus

Acute complications
Diabetic ketoacidosis.
Hypoglycemia.
Chronic complications
Retinopathy .
Nephropathy.
Neuropathy.
CV complications.(IHD)
Characteristic Type 1 ( 10% ) Type 2 ( 90% )
(Insulin dependent) (non-insulin dependent)

Onset (Age) Usually younger people < 30 Usually older people > 40
Puberty or early adulthood.
Type of onset Abrupt Gradual

Endogenous Absent Present, but relatively ineffective (Insulin

insulin (B cell are destroyed ) resistance) Reduced # insulin receptors
Or less responsive

Insulin therapy Required to avoid Required in only 20 - 30% of patients

hyperglycemia, ketoacidosis.

Hypoglycemic Should not be used Clinically indicated +diet.

drugs
Clinical Polydipsia , polyuria , Wt loss. Often asymptomatic
symptoms

Nutritional status Usually thin Usually obese

Ketosis Frequent (DKA) Usually absent

• Several comorbid conditions with type 2
DM:
 Coronary heart disease

 Obesity

 Dyslipidemia

 Hypertension

 Microalbuminemia (protein in the urine)

 Increased risk for thrombotic (blood clotting) events
Gestational Diabetes:

•Hyperglycemia that develops during pregnancy.

•Insulin must be given to prevent birth defects.

•Usually subsides after delivery.

•30% of patients may develop Type 2 DM within 10 to 15

years.
Diagnosis
Diagnosis
Diagnosis
 Treatment of diabetes mellitus:
• Type 1
Insulin therapy

• Type 2
Lifestyle changes
Oral drug therapy
Insulin when the above no longer provide glycemic
control
 Insulin
 Small protein, It has Two peptide chains A and B was linked by
disulfide bonds.

 ( A & B, of 21 & 30 amino acid residues ,respectively).

.Insulin and its analogs
Insulin
1. Rapid-Acting insulins:
lispro
aspart
glulisine.

•most rapid onset of action (roughly 15 minutes)

as well as a shorter duration of action than other
insulin categories.
2. Short-Acting insulin:
 Regular insulin.

•It is dosed via intravenous bolus, intravenous infusion.

• It is used in cases of DKA or coma associated with

uncontrolled type1 diabetes.
3. Intermediate-Acting insulin:
insulin isophane suspension NPH.

(neutral protamine Hagedorn insulin)

•The suspension appears cloudy.

•NPH is often combined with regular insulin to reduce

the number of insulin injections per day.
4. Long-Acting insulins:

Glargine clear, colorless solution, given once

or twice.

Detemir.
Fixed-Combination insulins:
 NPH 70% and regular insulin 30%

 NPH 50% and regular insulin 50%

 Insulin aspart protamine suspension 75% and insulin

aspart 25%

 Insulin lispro protamine suspension 75% and insulin

lispro 25%.

 All of these premixed; do not mix with other insulins.

 Insulin Administration
• SC usually ,IV in emergency

• Insulin Should be stored in refrigerator& warm up to

room temp before use.
• Must be used within 30 days (when opened).
:Usual places for injection
 Check blood glucose level before giving insulin

 When drawing up two types of insulin in one syringe,

always withdraw the regular or rapid-acting insulin
first
 Roll vials between hands instead of shaking them to
mix suspensions

 ONLY use insulin syringes, calibrated in units, to

measure and give insulin
.
 COMPLICATIONS OF INSULIN THERAPY

 Severe Hypoglycemia (< 50 mg/dl ) lead to

coma ,convulsions and even death.
 Overdose of insulin.
 Excessive (unusual) physical exercise.
 A meal is missed.

 Weight gain.

 Allergic reactions (rare).

 Lipodystrophy at injection sites.

• Hypoglycemia:
 early symptoms of CNS manifestations

confusion, irritability, tremor, and sweating.

 Later symptoms include hypothermia and seizures.

 If not managed….coma and death can occur.

• Glucose-Elevating Drugs:
 Oral forms of concentrated glucose: Buccal tablets, semisolid
gel

 50% dextrose in water (D50W)

 Glucagon
• Contraindications:

 drug allergy.

 In hypoglycemic patient.
• Interactions:
Drugs that anatagonize Drugs that increase
the hypoglycemic effects hypoglycemic effects of
:of insulin :insulin

thiazide and loop diuretics Alcohol

sympathomimitic drugs anabolic steroids

thyroid hormones sulfa drugs

Corticosteroids salicylates
• Beta-blockers may mask the signs and
symptoms of hypoglycemia (tachycardia,
tremor).

• Insulin increases the risk of hypoglycemia

when administered with other hypoglycemic
drugs.
ORAL ANTIDIABETIC
AGENTS
 Insulin Sensitizers -1
Improve target cell response to
insulin without increasing pancreatic
insulin secretion
 A. Biguanides (Metformin)
 first-line drug
• Mechanism of action:
 decreasing insulin resistance.
 Reduction of hepatic glucose output
(gluconeogenesis).
 Decreases the intestinal absorption of CHO
 improve insulin receptor sensitivity
>> cause moderate weight loss
• Contraindications:
 renal disease (Scr > 1.5 mg/dL)

 Alcoholism

 metabolic acidosis

 hepatic disease

 heart failure
• Adverse effects:

 Primarily affects GI tract: abdominal bloating, nausea,

cramping, diarrhea, feeling of fullness

 May also cause metallic taste, reduced vitamin B12

levels
 Lactic acidosis is rare but lethal if it occurs

 Does not cause hypoglycemia

B. Thiazolidinediones (glitazones):
Rosiglitazone

pioglitazone.

•Mechanism of action:
Increase insulin sensitivity in liver, adipose tissue, and
skeletal muscle.

•Side effects:
Moderate weight gain, edema, mild anemia

Hepatic toxicity—monitor ALT levels

2.Insulin Secretagogues
Promote insulin release from B-Cell
of the pancreas
Glipizide
Sulfonylureas Glimepiride
Glyburide.

Repaglinide
Glinides
Nateglinide
A. Sulfonylureas:
First-generation: Tolbutamide
Second generation (primary used now): glipizide,
glimepiride, and glyburide.

•Mechanism of action:
Stimulate insulin secretion
Improve sensitivity to insulin in tissues
• Indications: Because they have different mechanisms
of action, it can be used in combination with
metformin.

• Usually given 30 minutes before meals

• Adverse effects:
 Hypoglycemia
 weight gain
 skin rash
 epigastric fullness and heart burn.
B. Glinides (repaglinide and Nateglinide):
•Indication:

In combination with metformin or thiazolidinediones,

but not with sulfonylureas
•Adverse effects:

Hypoglycemia (which can occur particularly if food is not

taken after a dose).
 Weight gain.
3. Alpha-Glucosidase inhibitors
Acarbose
Miglitol.
•Mechanism of action:
• These drugs must be taken with food.
(with the first bite of each main meal)
• Used usually in combination

• Adverse effects:

 Flatulence

 diarrhea

 abdominal pain

>>> Do not cause hypoglycemia, hyperinsulinemia, or

weight gain
(4) New antidiabetic drugs:
A. Amylin mimetics (pramlintide):
• SC, Mimics the natural hormone amylin

• It is given S.C

• Used when other drugs have not achieved adequate

glucose control
B. Incretin mimetics (Exentide, Liraglutide).
• Weight gain and postprandial hyperglycemia are
reduced.
• HbA1c levels decline.

• Adverse effects:

 Nausea

 Vomiting

 Diarrhea

 constipation.
C. Dipeptidyl peptidase-IV (DPP-IV) inhibitors
( Sitagliptin (januvia) and vildagliptin (Galvus)):
 Taken once daily with or without food.

• Adverse effects:

 It is well tolerated

 Headache is the most common side effects.