Diabetes is a condition where the body has trouble processing blood sugar. It is important to manage blood sugar levels to avoid complications like heart disease and nerve damage. Oral antidiabetic drugs are medications that can help lower blood sugar levels for people with diabetes.

1. By-
Dr. Prerana B. Jadhav
M. Pharm, Ph.D.
Pharmaceutical Chemistry
Assistant Professor,
Sanjivani College of Pharmaceutical Education and
Research, Kopargaon.
ANTIDIABETIC
AGENTS

2. Introduction
• Diabetes mellitus (DM) is a metabolic disorder in which person has
high levels of glucose in blood.
• Type I DM Occurs when the pancreas cannot produce insulin, a
hormone essential for moving glucose from the blood into cells.
• Type II DM is a form of diabetes mellitus that is characterized
by high blood sugar, insulin resistance, and relative lack of insulin.
• Serious long term complications include -
Cardiovascular disease, nephropathy, retinopathy, and neuropathy.
• In India, about 1.6 million people are at risk of developing the
condition.
2

3. Introduction
• Some diabetic symptoms are frequent urination, excessive thirst, extreme
hunger, unusual weight loss, increased fatigue, irritability, and blurred vision.
Type 2 Diabetes Mellitus (T2DM) is controlled with
Sulfonylureas,
Meglitinides,
Thiazolidinediones,
Biguanides &
α – glucosidase inhibitors
3

4. CLASSIFICATION
1. Antidiabetic agents: Insulin and its preparations
2. Sulfonyl ureas: Tolbutamide, Chlorpropamide, Glipizide,
Glimepiride.
3. Biguanides: Metformin.
4. Meglitinides: Repaglinide, Nateglinide.
5. Glucosidase inhibitors: Acrabose, Voglibose.
6. DPP IV inhibitors: Sitagliptin, Teneligliptin
7. SGLT2 inhibitors: Empagliflozin, Canagliflozin

5. INSULIN
• Insulin, a pancreatic hormone, is a specific
antidiabetic agent, especially for type-I diabetes.
• Human insulin is a double-chain protein that
contains 51 amino acids (chain A-21 amino acids,
and chain B-30 amino acids), which are bound
together by disulphide bridges.

6. • In the body, insulin is synthesized by β cells of Langerhans islets in the pancreas.
• In β cells, insulin is synthesized from the proinsulin precursor
molecule (pro-insulin consists of three domains: an amino-terminal
B chain, a carboxy-terminal A chain, and a connecting peptide in
the middle known as the C peptide) by the action of proteolytic
enzymes, known as prohormone convertases (PC1 and PC2),as well
as the exoprotease carboxypeptidase E. These modifications of pro-
insulin remove the centre portion of the molecule (i.e., C peptide)
from the C- and N-terminal ends of pro-insulin.
• The remaining polypeptides (51 amino acids in total), the B- and A-chains, are
bound together by disulphide bonds.

7. MOA of Insulin
• Insulin acts by binding with specific receptors on the
surface of the insulin-sensitive tissues such as skeletal
muscle, cardiac muscle, fatty tissue, and leukocytes. Insulin
lowers the sugar content in the blood by turning glucose
into glycogen.
• Using insulin in diabetes mellitus leads to lower levels of
sugar in the blood, and a build-up of glycogen in tissues.

8. • Insulin is usually taken as subcutaneous
injections by single-use syringes with needles.

9. Oral hypoglycaemic agents
• Antidiabetic drugs are drugs that lower the level of glucose (sugar)
in the blood.
• Sulfonylureas: Tolbutamide, Chlorpropamide, Glipizide,
Glimepiride.
• Biguanides: Metformin.
• Meglitinides: Repaglinide, Nateglinide.
• Glucosidase inhibitors: Acrabose, Voglibose.
• DPP IV inhibitors: Sitagliptin, Teneligliptin
• SGLT2 inhibitors: Empagliflozin, Canagliflozin

10. Sulfonylureas
• Discovery
• The compound 2-(p -aminobenzenesulphonamido)-5-isopropyl -thiadiazole
(IPTD) was used in the treatment of typhoid fever in the early 1940s.
• However, many patients died from being treated with heavy doses of the drug.
• These deaths were eventually attributed to acute and prolonged hypoglycaemia.
• IPTD did not come to be used as hypoglycaemic agents because a second drug,
carbutamide, was found to be an effective oral hypoglycaemic agent.
• Carbutamide was more active than IPTD and was the first sulphonylurea
hypoglycaemic agent to be marketed.

11. Mechanism of action
• Sulphonylureas bind to an ATP-dependent K+ channel on
the cell membrane of pancreatic β cells.
• This inhibits outflux of potassium, which causes the
electric potential over the membrane to become more
positive. This depolarization opens voltage-gated Ca2+
channels.
• The rise in intracellular calcium leads to increased fusion of
insulin granulae with the cell membrane, and therefore,
increased secretion of insulin..

18. Biguanides: Metformin
• This class of agent is capable of reducing sugar absorption
from gastrointestinal tract.
• They decrease gluconeogenesis while increasing glucose
uptake by muscles and fat cells. This will lead to lower the
blood glucose levels.

19. α-Glucosidase inhibitors
• The enzyme α-Glucosidase is present in the brush
border of the small intestine and is responsible for
cleaving dietary carbohydrates and facilitating
their absorption into the body.
• Inhibition of this enzyme allows less dietary
carbohydrate to be available for absorption and less
available in the blood.

20. Acarbose
• It is naturally occuring oligosaccharide obtained
from the microorganism Actinoplanes utahensis.
• It is competitive inhibitor of α-Glucosidase which
reduces the intestinal absorption of starch, dextrin
and disaccharides.

21. Voglibose
• Voglibose is an alpha-glucosidase
inhibitor used for lowering postprandial blood
glucose levels in people with diabetes
mellitus.

22. Meglitinides: Repaglinide,
Nateglinide.
• The metaglinides are nonsulfonylurea oral hypoglycemic agents used in the
management of type 2 diabetes.
• These agents end to have a rapid onset and a short duration of action.
• Much like the sulfonylureas, these induce insulin release from functioning
pancreatic ẞ cells.
• The mechanism of action is through binding specific receptors in
the B-cell membrane, leading to the closure of ATP-dependent
K+ channels. The K channel blockade depolarizes the B-cell
membrane, which in turn leads to Ca2+ influx, increased
intracellular Ca2+ and stimulation of insulin secretion.

23. • The effect of metaglinides do not last as long as
effect of sulphonylureas.
• The effects of this class appear to last less than 1
hour, whereas sulphonylureas continue to
stimulate insulin production for several hours.
• One advantage of short duration of action is less
risk of hypoglycemia.

24. Repaglinide
• Fast onset and short duration of action.
• It should be taken with meal.
• It is oxidized by CYP 3A4. Less than 0.2% is excreted
unchanged by the kidney which is advantage for elderly
patients who are renally impaired.
• Side effects: Headache, cold sweats, anxiety and changes in
mental state.

25. Nateglinide
• It is phenylalanine derivative and represents a
novel drug in the management of type 2
diabetes.
• Nateglinide is used alone or in combination
with other medications to treat type 2
diabetes.

26. • Side effects:
• Hypoglycemia
• dizziness
• sweating
• nervousness
• sudden changes in behavior or mood
• Headache
• weakness
• pale skin
• hunger
C
H3
C
H3 O
NH
OH
O

27. DPP IV inhibitors
• Incretin hormones, such as GLP-1. These are rapidly secreted
from the gut following food intake.
• GLP-1 is responsible for metabolism of glucose and glucose
reuptake from body. It is rapidly get destroyed by the enzyme
DPP IV.
• Dipeptidyl-peptidase IV inhibitors inhibit the degradation of the
incretins, glucagon-like peptide-1 (GLP-1) and glucose-
dependent insulinotropic peptide (GIP).
• Prolong the action of incretin hormones.

28. DPP IV inhibitors
Sitagliptin Teneligliptin
F
F
NH2 O
N
N
N
N
F
F
F
F

29. Advantages of DPP IV inhibitors
• Safety
DPP-4 inhibitors are generally well tolerated and have a low risk of hypoglycemia.
• Efficacy
DPP-4 inhibitors are effective at reducing blood glucose levels and improving glycemic
control.
• Mechanism of action
DPP-4 inhibitors work by stimulating the secretion of insulin in response to glucose.
• Heart health
DPP-4 inhibitors may have a protective effect on the heart. For example, sitagliptin may
improve heart function and coronary artery perfusion in diabetic patients with coronary
heart disease

30. SGLT2 inhibitors: Empagliflozin,
Canagliflozin
• Sodium-glucose cotransporter 2 (SGLT2) inhibitors that
are used to treat type 2 diabetes.
• SGLT2 inhibitors lower blood sugar by preventing the
kidneys from reabsorbing glucose. This causes the body to
remove excess glucose through urine.
• SGLT2 inhibitors can improve glycemic control, reduce the
risk of cardiovascular complications, and slow the
progression of diabetic kidney disease.

31. • Side effects:
Urinary frequency, dehydration, genitourinary
tract infections, and rarely, diabetic
ketoacidosis

32. Canagliflozin
• Canagliflozin was the first SGLT-2 inhibitor approved on March 29,
2013;
• It is indicated in adult patients with type 2 DM to improve blood
glucose control in addition to diet and exercise.
• It is also shown to decrease the risk of cardiovascular (CV) adverse
events in type 2 DM subjects with underlying CV illness and
minimize the risk of end-stage renal disease
• The initial dose is 100 mg once daily and may be increased to 300
mg daily.

33. • Canagliflozin

34. Empagliflozin
• Empagliflozin was the third SGLT inhibitor to receive approval from
the FDA in August 2014.
• Empagliflozin is indicated in adult patients with type 2 DM to
improve the control of blood glucose in addition to diet and
exercise, decrease the risk of CV adverse events in type 2 DM
subjects.
• The initial dose is 10 mg once daily; the dose may be increased to
25 mg daily to achieve the targeted glycemic goal.

35. Empagliflozin