Oral hypoglycemic drugs are used to treat type 2 diabetes and work by lowering blood glucose levels. There are 5 classes of oral hypoglycemic drugs currently used: sulfonylureas, biguanides, meglitinides, thiazolidinediones, and alpha-glucosidase inhibitors. Sulfonylureas like glipizide stimulate insulin secretion from the pancreas. Biguanides like metformin reduce glucose production and absorption. Meglitinides and sulfonylureas both stimulate insulin secretion but meglitinides have a faster onset and shorter duration. Thiazolidinediones like pioglitazone increase insulin sensitivity. Alpha-glucosidase inhibitors

1. BY,
SARANG
SREE RAMACHANDRA COLLEGE OF PHARMACY 1
ORAL
HYPOGLYCAEMIC
DRUGS

2. Oral hypoglycemics
• Drugs that are given orally to reduce the blood
glucose levels in diabetic patients
• Five types of oral antidiabetic drugs are
currently in use:
• Sulfonylureas
• Biguanides
• Meglitinides
• Thiazolidinediones
• Alpha -glucosidase inhibitors
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3. 3

4. Sulfonylureas
I Generation
– Tolbutamide
– Chlorpropamide
II Generation
– Glipizide
– Gliclazide
– Glibenclamide (Glyburide)
– Glimepiride
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5. First Generation
Tolbutamide
• O.O.A. is within one hour & lasts for 6-12 Hrs
• It is weaker, short acting, less likely to cause hypoglycemia
Chlorpropamide
• O.O.A. is within one hour & lasts for 24-60 Hrs
• It is more potent, long lasting, risk of prolonged hypoglycemia
• Potentiates ADH action
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6. Second Generation
Glibenclamide (glyburide)
• O.O.A. is within 1-4 hours & lasts for 10-24 Hrs
• It is more potent than tolbutamide, risk of severe hypoglycaemia.
Glipizide
• O.O.A. is within 1-3 hours & lasts for 10-24 Hrs
• Less potent than glibenclamide but more potent than tolbutamide
• Risk of prolonged hypoglycemia
Gliclazide
• O.O.A. & D.O.A, same as glipizide
• More potent than tolbutamide
• Has an antioxident and antiplatelet action
• Less weight gain
Glimepiride:
• Same as glipizide
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7. Sulfonylureas -
MOA
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8. Sulphonylureas
 Pharmacokinetics
• Well absorbed
• PPB is high
• Metabolized in liver or kidney and excreted in urine
 Adverse effects
• Hypoglycemia
• Weight gain
• Cross placental barrier – fetal hypoglycemia (avoid in gestational DM)
 Contra indications
• Ketocanazole, chloramphenicol and anticoagulants- inhibit their metabolism
• Sulfonamides, salicylates etc- protein binding displacement
• Propranolol masks the symptoms of sulfonylureas
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9. BIGUANIDES
Metformin :
• The primary drug of choice for diabetes by ADA guidelines.
Dose: 0.5 to 2.5 g/day in 2-3 divided doses
Phenformin : Its use has been discontinued because of lacticacidosis
MOA:
• Suppress hepatic & renal gluconeogenesis
• Increases uptake & utilization of glucose by skeletal muscles
which reduces insulin resistance
• Inhibit alimentary absorption of glucose
• Interfere with mitochondrial respiratory chain & promote
peripheral glucose utilization by enhancing anaerobic
glycolysis.
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10. • PHARMACOKINETICS:
• Taken orally, well absorbed through GI tract
• Not metabolized at all
• Excreted unchanged in urine
• INDICATIONS:
• Obese Type 2 Diabetes.
• Secondary Sulfonylurea Failure state.
• To reduce Insulin requirements.
• Can be combined with Sulfonylureas, Glitazones,
Insulin.
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11. ADVERSE EFFECT:
• Anorexia, nausea, vomiting, diarrhoea
• Metallic taste
• Loss of weight
• Skin rashes
• Lactic acidosis: rare
• Vitamin B12 deficiency: due to malabsorption
• Usually does not cause hypoglycemia even in large doses
Contraindications:
• Renal failure
• Advanced Liver Disease.
• Alcohol abusers.
• Cardiac Disease.
• Pregnancy.
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12. Meglitinide analogs
• This class of agents includes repaglinide and
nateglinide. Although they are not sulfonylureas, they
have common actions.
MOA:
• Their action is dependent on functioning pancreatic β cells.
• They bind to a distinct site on the sulfonylurea receptor of ATP-
sensitive potassium channels, thereby initiating a series of
reactions culminating in the release of insulin.
• However, in contrast to the sulfonylureas, the meglitinides have a
rapid onset and a short duration of action.
• They are are categorized as postprandial glucose regulators.
• Meglitinides should not be used in combination with sulfonylureas
due to overlapping mechanisms of action.
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13. Pharmacokinetics:
• These drugs are well absorbed orally after being taken 1
to 30 minutes before meals.
• Both meglitinides are metabolized to inactive products by
CYP3A4 in the liver.
• Excreted through the bile.
Adverse Effects:
• Incidence of hypoglycemia is lower than that of the
sulfonylureas.
• Repaglinide has been reported to cause severe
hypoglycemia in patients who are also taking the lipid-
lowering drug gemfibrozil.
• Weight gain is less of a problem with the meglitinides
than with the sulfonylureas.
• Must be used with caution in patients with hepatic
impairment.
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14. Thiazolidinediones (Glitazones)
Rosiglitazone & pioglitazone Selective agonists of PPAR
Bind to nuclear PPARγ
Activate insulin responsive genes -
regulate carbohydrate & lipid metabolism
Sensitize the peripheral tissues to insulin
↓blood glucose by
↑ Glucose transport
into muscle & adipose
tissue
Inhibit hepatic
gluconeogenesis
Promote
lipogenesis14

15. • Pharmacokinetics:
• Both pioglitazone and rosiglitazone are absorbed very
well after oral administration and are extensively bound
to serum albumin.
• Both undergo extensive metabolism by different
cytochrome P450 isozymes.
• Pioglitazone:
• Renal elimination is negligible, with the majority of the
active drug and metabolites excreted in the bile and
eliminated in the feces.
• Rosiglitazone:
• The metabolites are primarily excreted in the urine.
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16. • Adverse Effects:
• Very few cases of liver toxicity have been reported with
rosiglitazone or pioglitazone.
• Weight increase can occur, possibly through the ability of
TZDs to increase subcutaneous fat or due to fluid
retention.
• Glitazones have been associated with osteopenia and
increased fracture risk.
• Other adverse effects include headache and anemia.
• DOSE:
• Pioglitazone: 15 to 45 mg once daily orally
• Rosiglitazone: 4 to 8 mg once daily orally
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17. α-glucosidase inhibitors
• Alpha-glucosidase inhibitors works by preventing the
digestion of carbohydrates (such as starch and table
sugar).
• Hence, alpha-glucosidase inhibitors reduce the impact of
carbohydrates on blood sugar.
• Acarbose and miglitol are orally active drugs used for
the treatment of patients with Type 2 diabetes.
Dose:
• Acarbose - 50mg to 100mg TDS
• Miglitol - 25mg to 100mg TDS
• Voglibose - 0.2 to 0.3 mg TDS
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18. • MOA:
• These drugs are taken at the beginning of meals.
• They act by delaying the digestion of carbohydrates,
thereby resulting in lower postprandial glucose levels.
• Both drugs exert their effects by reversibly inhibiting
membrane-bound α-glucosidase in the intestinal brush
border.
• This enzyme is responsible for the hydrolysis of
oligosaccharides to glucose and other sugars.
• Consequently, the postprandial rise of blood glucose is
blunted.
• Unlike the other oral hypoglycemic agents, these drugs
do not stimulate insulin release, nor do they increase
insulin action in target tissues.
• Thus, as monotherapy, they do not cause hypoglycemia.
• However, when used in combination with the
sulfonylureas or with insulin, hypoglycemia may develop.
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19. PHARMACOKINETICS:
• Acarbose is poorly absorbed. It is metabolized primarily
by intestinal bacteria, and some of the metabolites are
absorbed and excreted into the urine.
• On the other hand, miglitol is very well absorbed but has
no systemic effects. It is excreted unchanged by the
kidney.
ADVERSE EFFECTS:
• The major side effects are flatulence, diarrhea, and
abdominal cramping. Patients with inflammatory bowel
disease, colonic ulceration, or intestinal obstruction
should not use these drugs
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20. What is the role of an ideal oral
hypoglycaemic agent?
• Conserve islet cell function - delay the subsequent
use of insulin.
• Improve patient compliance- single daily dosing.
• Reduce the incidence of hypoglycaemic events
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21. Adverse effects of OHAs
Meglitinide
Sulfonylureas
Hypoglycemia
Biguanides
α-Glucosidase inhibitors
GI disturbance
Biguanides
Nausea
Thiazolidinediones
Risk of hepatotoxicity
Sulfonylureas
Meglitinides
Thiazolidinediones
Weight gain
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22. THANK
YOU
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