Maharshi Dayanand University, Rohtak
Department of Pharmaceutical Sciences
Topic - Oral Hypoglycemic Drugs
Submitted To: Dr. Govind Singh Submitted By :Manish Yadav
Associate professor(P’Cology) Roll no : 4101
M. Pharm ( Pharmacology)
Oral Hypoglycemic Drugs
Definition : Oral antihyperglycemic agents lower glucose levels in the blood. They are
commonly used in the treatment of diabetes mellitus.
By the end of the lecture , you should know:
● Classify different categories of antidiabetic drugs.
● Identify mechanism of action, pharmacokinetics and pharmacodynamics of each class of
● Identify the clinical uses of antidiabetic drugs
● Know the side effects, of each class of antidiabetic
Types of diabetes mellitus
Type II VS Type I
Due to obesity & genetic factors . Due to autoimmune or viral
-80-90% occurrence diseases (the only treatment for insulin
-Over age 35 dependent diabetes is insulin injections)
Patients with Type II diabetes have two physiological
1. Abnormal insulin secretion. (partial production of insulin)
2. Resistance to insulin action in target tissues associated with decreased number of
Treatment of Type II Diabetes
Stage 1 Stage 4.
Stage 2 Stage 3.
weight loss are
IMP in obese
General trick to manage
Type 2 diabetes is managed through a stepwise approach
Step1. Starting with diet and exercise than .
Step 2. followed by oral hypoglycemic drugs.
Step 3. Then combination therapy if the patient is not responding to monotherapy of
Step 4. And finally in advanced severe cases insulin injections are used.
Step 5. They increase the production of insulin.
Step6 . They increase the sensitivity of peripheral tissues to insulin.
● Are drugs which increase the amount of insulin secreted by the pancreas
★ Their action depends upon functioning pancreatic β-cells .
● It includes: a. Sulfonylureas
( 1-1) sulfonylureas
Class First generation (-amide) Second generation (-ride/ zide)
Drug -Acetohexamide - Tolbutamide - Glyburide (glibenclamide) - Gliclazide
- Glimepiride - Glipizide
Long acting Short acting Long acting (-ride) Short acting (-zide)
P.K ● Orally -- well absorbed.
★ All are highly bound to -- plasma proteins.
● Excreted in-- urine .
★ Cross placenta, stimulate fetal β-cells to release insulin → fetal hypoglycemia at birth.
● Reach peak concentration after-- 2-4 hr
● Duration of action is variable
● Metabolized in-- liver
Uses ● Treatment of Type II diabetes-- monotherapy or in combination with other
antidiabetic drugs .
ADR 1. Hyperinsulinemia & Hypoglycemia:
○ More common in long acting sulfonylureas; particularly (glyburide, and glimepiride)
○ More in old age, hepatic or renal diseases.
2. Weight gain due to increase in appetite unless the diabetic diet and exercise program
NOTE: 1. All hypoglycemic drugs are C.I during pregnancy, even if the patient was
diagnosed with type 2 diabetes.
2. The only treatments that is allowed during pregnancy is insulin.
Step1 : Sulfonylureas
Step2 : Bind to specific receptor on Beta cell of islets of pancreas
Step 3: Blockade of ATP dependent K+ channels
Step4 : Opening of voltage-dependent Ca+ channels
Step 5: By depolarization and influx of calcium ions into Beta cell
Step 6 ↑Intracellular calcium in the beta cell
Step 7: By Degranulation and increased release of stored insulin from Beta cell
Step 8: ↑Insulin release in blood
( 1-2) Meglitinides
Drug -- Repaglinide
P.K ● Orally, well absorbed.
★ Very fast onset of action, peak 1 h.
● Short duration of action (4 h).
● Metabolized in liver and excreted in bile.
★ Taken just before each meal (3 times/day)
○ The dose should be skipped if the meal is missed 1
Uses ● Type II diabetes as a monotherapy or in combination with other oral hypoglycemic drugs
ADR ● Less incidence than sulfonylureas 2
○ Weight gain
MOA : Meglitinides
,Meglitinides (glinides) are based on the sulfonylurea moiety of glibenclamide (called meglitinide).
They bind to the SUR1 receptor on the β-cell, although with lower affinity than sulfonylureas,
and stimulate insulin release in the same way.
Note : 1 Sulfonylurea monotherapy is associated with higher risk for all-cause mortality, major
hypoglycemic episodes, and cardiovascular events compared with metformin
2. Meglitinides are secretagogues like sulfonylureas, although not structurally related
.Note: Sulfonylureas and meglitinides
Sulfonylureas and meglitinides directly stimulate release of insulin from
pancreatic beta cells and thereby lower blood glucose concentrations.
Because they work by stimulating insulin secretion, they are useful only in
patients with some beta cell function
1.Biguanides -- Drug -- Metformin
P.K ● Orally
● Not bound to serum protein,
.t 1⁄2: 3 hours.
● Not metabolized, excreted unchanged in urine
★ No risk of hypoglycemia2
● No weight gain
★ In patients with type 2 diabetes who are obese because it promotes
modest weight reduction (first-line therapy).
● Type 2 diabetes as monotherapy or in combination with other antidiabetics.
● GIT disturbances:
○ Metallic taste in the mouth, nausea, vomiting, diarrhea
○ Metformin should be taken with meals and should be started at a low dose to avoid
intestinal side effects then increase gradually.
★ Lactic acidosis 5 (very rare):
● In long term use: Interference with vitamin B12 absorption8
MOA : Metformin
• 1 . Decreases the liver's production of glucose via activation of AMP-activated protein kinase
(AMPK) Adenosine Monophosphate-Activated Protein Kinase
• 2. Other possible mechanism may contribute to its effects, and include:
• inhibiting the breakdown of fatty acids used to produce glucose
• at very high doses it may increase the removal of glucose from muscle, the liver, and other body tissues
where it is stored.
( 2- 2) Thiazolidinediones
Drug -- Pioglitazone & Rosiglitazone (-glitazone)
P.K ● Orally (once daily dose).
● Highly bound to plasma albumins (99%)
● Slow onset of activity
● Half life 3-4 h 2
● Metabolized in the liver
● Excreted in bile and urine
Uses ● Type II diabetes with insulin resistance.
● Used either alone or in combination with sulfonylurea, biguanides or insulin.
★ No risk of hypoglycemia when used alone
ADR ● Hepatotoxicity (monitor liver function tests for 1st year of therapy).
★ Fluid retention (Edema)
★ Congestive heart failure3
● Mild weight gain
● Failure of estrogen-containing oral contraceptives
MOA: Thiazolidinediones :They increase sensitivity of
peripheral tissue to insulin
Step 1: Pioglitazone ( drug )
Step 2: Bind to nuclear PPAR-y
Step 3: . Activate peroxisome proliferator-activated receptor-Gamma (PPAR-Gamma.
Step 4: Activate insulin –responsive gene that regulate carbohydrate and lipid metabolism
Step 5: ● Increase sensitivity of target tissues ( peripheral tissue ) to insulin.
Step 6: ● Increase glucose uptake or transport into muscle cell and adipose tissue
.utilization in muscle and adipose tissue
.inhibit hepatic gluconeogenesis.
Class- 3. α-Glucosidase inhibitors
Drug -- Acarbose , Miglitol
P.K ● No hypoglycemia if used alone
● Given orally, not absorbed so taken just before meals.
Uses ★ Are effective alone in the earliest stages of impaired glucose tolerance
● Are not recommended alone as therapy for moderate to severe hyperglycemia
○ Most useful in combination with other oral hypoglycemic drugs or with insulin.
ADR ● GIT: Flatulence, bloating, diarrhea, abdominal pain.
MOA: . α-Glucosidase inhibitors
Reversible inhibitors of intestinal α-glucosidases in intestinal brush border cells
that are responsible for carbohydrate digestion.
● Decrease carbohydrate digestion and glucose absorption in small intestine
(lower postprandial glucose level).
Class 4. Sodium-glucose transporter 2 inhibitors
Drug ---- Canagliflozin, Dapagliflozin, Empagliflozin (-gliflozin)
● Used with diet and exercise to control high blood sugar in patients with type 2 diabetes.
● To reduce risk of major adverse cardiovascular events1 in adults with type 2
diabetes and established cardiovascular disease.
★ Urinary tract infections.
★ Yeast infections2 (vagina or penis)
● Increased urination and dry mouth.
● Itching (vagina or penis)
MOA:Sodium-glucose transporter 2 inhibitors
Inhibits SGLT2 in the kidneys
inhibits glucose and Na reabsorption
this allows excess glucose to be excreted
in the urine→ this will reduce blood sugar levels.
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Progression of Hyperglycemia in Zucker Diabetic Fatty Rats. J Pharmacol Exp Ther 351:423-431.
McCulloch DK (2014): Management of persistent hyperglycemia in type 2 diabetes mellitus. In:
UpToDate, Basow, DS (Ed), Waltham, MA. Cited 6/16/14.
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cardioVascular Assessment Study-Renal (CANVAS-R): A randomized, placebo-controlled trial.
Diabetes Obes Metab.