INSULIN AND ANTIDIABETIC DRUGS

BSc nursing online and offline lecture series

Dr. Sayan Chatterjee : 3rd year MD PGT : Pharmacology : IPGME&R
 OVERVIEW
INTRODUCTION

PATHOPHYSIOLOGY OF HYPERGLYCAEMIA IN T2DM

OMINOUS OCTET OF T2DM

CLASSIFICATION

ORAL AND INJECTABLE DRUGS

INSULIN AND ITS ADMINISTRATION

SUMMARY

Bsc nursing pharmacology lecture series: Dr. Sayan Chatterjee 2

INTRODUCTION
Type II diabetes mellitus : definition

Group of heterogenous disorders characterized by hyperglycaemia

(resulting from defects in insulin secretion, insulin action or both) and
increased lipid and protein metabolism

Types

• Type 1 diabetes mellitus

• Type 2 diabetes mellitus

• Gestational diabetes mellitus

• Others
Source:
Bsc nursing pharmacology lecture series: Dr. Sayan Chatterjee 3
INTRODUCTION

Bsc nursing pharmacology lecture series: Dr. Sayan Chatterjee 4

GLOBAL BURDEN

Source: Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications.
Nat Rev Endocrinol. 2018;14(2):88-98.
Bsc nursing pharmacology lecture series: Dr. Sayan Chatterjee 5
PATHOPHYSIOLOGY OF HYPERGLYCAEMIA IN
T2DM

Source: Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications.
6
Nat Rev Endocrinol. 2018;14(2):88-98. Bsc nursing pharmacology lecture series: Dr. Sayan Chatterjee
OMINOUS OCTET OF T2DM

Bsc nursing pharmacology lecture series: Dr. Sayan Chatterjee 7

CLASSIFICATION
Binds to sulfonylurea receptors and stimulates insulin release

• Sulfonylureas
• Meglitinides

Actions on liver, muscle and adipose tissue ; glucose ↓

• Biguanides
• Thiazolidinediones

Absorption of glucose ↓

• α-glucosidase inhibitors

Mimics incretins or prolong incretin action

• GLP-1 agonists
• DPP-4 inhibitors
SGLT2 inhibitors

Others
Bsc nursing pharmacology lecture series: Dr. Sayan Chatterjee 8
CLASSIFICATION
ORAL ANTIDIABETIC AGENTS INJECTABLES

BIGUANIDES Metformin Exenatide

GLP-1 Liraglutide
SULFONYLUREAS Glipizide, Glimepiride, AGONISTS Albiglutide
Gliclazide
ISLET Pramlintide
MEGLITINIDES Repaglinide AMYLOID
POLYPEPTIDE
Nateglinide ANALOG

α- GLUCOSIDASE Acarbose Rapid acting

• Lispro
INHIBITORS Voglibose • Aspart
• Glulisine
THIAZOLIDINEDIONES Pioglitazone • Inhaled regular
Rosiglitazone Short acting
• Regular insulin
DPP-4 INHIBITORS Sitagliptin Intermediate acting
Linagliptin • NPH
INSULIN Long acting
Vildagliptin
• Detemir
• Glargine
SGLT2 INHIBITORS Canagliflozin
• Degludec
Dapagliflozin

BILE ACID Colesevelam

SEQUESTRANT
DOPAMINE AGONIST Bromocriptine 9
 BIGUANIDES METFORMIN

AMP activated protein kinase ↓ hepatic glucose production

↓ FBS; ↓ PPBS ; chances of hypoglycaemia rare during metformin therapy

t1/2 = 1.5-3 hrs; non plasma protein bound; not metabolized; excreted by kidneys as an
active compound

↓ gluconeogenesis  ↓hepatic metabolism of lactic acid

Renal insufficiency metformin accumulates↑↑risk of lactic acidosis

1st line drug for T2DM : insulin sparing effect : no weight gain or loss : chances of
hypoglycaemia ↓ : ↓risk of micro- and macrovascular diseases

↓risk of T2DM in middle aged and obese patients

Initiating dose: 500mg daily; max: 2.55mg daily

Source: Katzung, B. G., Kruidering-Hall, M., & Trevor, A. J. (2019). Katzung & Trevor's pharmacology: Examination & board review
(Fourteenth edition.). New York: McGraw-Hill Education. 10
 BIGUANIDES METFORMIN

Toxicities:
• GI : anorexia, nausea, vomiting, diarrhea, abdominal discomfort
• Vit B12 ↓ after prolonged metformin therapy( can be prevented by
intake of calcium)
• Lactic acidosis

Use caution with dose and follow renal function closely(every 3-6
eGFR > 45-59
months)
Max dose 1000mg/day or use 50% dose reduction. Follow renal
eGFR > 30-44
function every 3 months. Do not start as new therapy
eGFR < 30 Avoid use

Source: Katzung, B. G., Kruidering-Hall, M., & Trevor, A. J. (2019). Katzung & Trevor's pharmacology: Examination & board review
(Fourteenth edition.). New York: McGraw-Hill Education. 11
SULFONYLUREAS
 Insulin secretagogue
 Requires at least 30% functional β cells
• Glibenclamide, Glicazide, Glipizide, Glimepiride
• MOA: ↑ insulin secretion by acting on sulfonylurea receptor at ATP sensitive K+
channel
• Acts by blocking the K+ ATP channel that reduces influx of rectifying K+ ion current &
causes partial depolarization of pancreatic beta-cells increased influx of Ca++ ions as
well as release of Ca++ from intracellular stores & promotes exocytotic release of
insulin.
• Chronic use: sensitize the target tissue to the action of insulin
• Slow hepatic degradation of insulin
• Reduces glucagon secretion

Bsc nursing pharmacology lecture series: Dr. Sayan Chatterjee 12

SULFONYLUREAS

Pharmacokinetics:
• Well absorbed orally
• High plasma protein bound (90%)
• Single daily dose is sufficient
Adverse Effects:
• Hypoglycaemia
• Non specific Side effects: weight gain, nausea, vomiting,
flatulence, diarrhoea, constipation, headache, paresthesia
• Hypersensitivity: Rashes, photosensitivity, purpura, transient
leukopenia, rarely agranulocytosis
• SU + alcohol: flushing, disulfiram-like reaction

Bsc nursing pharmacology lecture series: Dr. Sayan Chatterjee 13

MEGLITINIDE/PHENYLALANINE ANALOGUES

Mechanism of Action:
• K+ ATP channel blockers; quick and short lasting
action
• Normalises meal time glucose levels

Repaglinide and Nateglinide:

• Quickly absorbed and rapidly metabolised
• Administered before each major meal, omit if meal
missed.
• Lower incidence of hypoglycaemia
Indication:
• Type 2 DM with pronounced postprandial
hyperglycaemia
• Along with Metformin/long acting insulin
S/E: Mild headache, dyspepsia, arthralgia weight gain
Avoided in liver disease!

Bsc nursing pharmacology lecture series: Dr. Sayan Chatterjee 14

 GLUCAGON-LIKE PEPTIDE-1 (GLP) RECEPTOR AGONISTS
MOA: GLP-1 is an important incretin released
from the gut in response to ingested glucose. It
induces insulin release from pancreatic β cells,
inhibits glucagon release from α cells, slows
gastric emptying and suppresses appetite.

Exenatide:
•Synthetic dipeptidyl peptidase-4 (DPP-4)
enzyme resistant analogue.
• Activates GLP receptors
• Cannot be given orally
• Used as an add-on drug to
metformin/SU/Pioglitazone
•Lowers postprandial as well as fasting blood
glucose, HbA1c and body weight
S/E: nausea/vomiting, tolerance develops later

Liraglutide:
• Highly bound to plasma proteins: longer duration
of action

Bsc nursing pharmacology lecture series: Dr. Sayan Chatterjee 15

DIPEPTIDYL PEPTIDASE-4 (DPP-4) INHIBITORS

DPP-4 enzyme causes rapid degradation of endogenous GLP- 1, thus

orally active inhibitors of this enzyme have been developed as
indirectly acting insulin secretagogues.

Sitagliptin:
• MOA: Acts as competitive and selective DPP-4 inhibitor &
potentiates the action of GLP-1 and GIP.
• Boosts postprandial release, decreases glucagon secretion and lowers
meal time as well as fasting blood glucose in Type 2DM
• Body weight neutral, low risk of hypoglycaemia
• Well absorbed orally, little metabolised, largely excreted unchanged
in urine
• Dose reduction needed in renal dysfunction
• S/E: nausea, loose stools, headaches, rashes, allergic reactions,
edema

Bsc nursing pharmacology lecture series: Dr. Sayan Chatterjee 16

THIAZOLIDINEDIONES (PPARγ ACTIVATOR)

MOA: Pioglitazone is selective agonist for the nuclear peroxisome

proliferator-activated receptor γ (PPARγ) expressed mainly in fat cells,
and in muscle cells. It enhances transcription of insulin responsive
genes & tends to reverse insulin resistance by enhancing GLUT4
receptor expression and translocation.
• Suppresses hepatic gluconeogenesis
• Additionally, lowers serum triglyceride, raises HDL
• Well tolerated
S/E: plasma volume expansion, edema, weight gain, headache,
myalgia, mild anaemia, increased risk of fracture esp. in elderly
women
Contraindicated in liver disease and in CHF

Bsc nursing pharmacology lecture series: Dr. Sayan Chatterjee 17

α GLUCOSIDASE INHIBITORS

Acarbose:
MOA: Inhibits α-glucosidases (enzyme responsible for digestion of
carbohydrates in the brush border of small intestine mucosa) slow
down and decrease digestion and absorption of polysaccharides and
sucrose. Dose 50–100 mg TDS is taken at the beginning of each major
meal. Additionally it promotes GLP-1 release.

S/E: Flatulence, abdominal discomfort, loose stool; Poor patient

acceptability
Miglitol: It has a smaller molecule than acarbose, and it is a stronger
inhibitor of sucrase. Potency for other α-glucosidases is equivalent to
acarbose. Dose: 25–100 mg TDS at beginning of each meal.
Voglibose: It has properties, use and side effects similar to that of
acarbose. Dose: 0.2–0.3 mg TDS just before meals.

Bsc nursing pharmacology lecture series: Dr. Sayan Chatterjee 18

INSULIN
Insulin was discovered in 1921 by Banting and Best

Insulin is a two chain polypeptide having 51 amino acids

and MW about 6000. The A-chain has 21 while B-chain
has 30 amino acids

The overall effects of insulin are to dispose meal

derived glucose, amino acids, fatty acids and
favour storage of fuel. It is a major anabolic
hormone: promotes synthesis of gylcogen, lipids and
protein

Source: Essentials of medical pharmacology; K.D. Tripathi 8th ed.

Bsc nursing pharmacology lecture series: Dr. Sayan Chatterjee 19
INSULIN TYPES

Aspart, lispro, glulicine

01Rapid-acting

Regular human insulin

02Regular or Short-acting
NPH Intermediate acting
03
Glargine,
Longdetemir
04 acting

Degludec, Glargine U300

05 Ultra long acting
Source:
Bsc nursing pharmacology lecture series: Dr. Sayan Chatterjee 20
INSULIN TYPES

Bsc nursing pharmacology lecture series: Dr. Sayan Chatterjee 21

INSULIN INDICATIONS FOR T2DM
Pregnancy (preferably prior to pregnancy)

Acute illness requiring hospitalization

Perioperative/ ICU setting

Post MI

High dose glucocorticoid therapy

Inability to tolerate or contraindications to oral antidiabetic agents

Newly diagnosed T2DM with significantly ↑blood glucose levels (severe

symptoms/DKA)
Patient no longer achieving therapeutic goals on combination antiglycemic therapy
22
Bsc nursing pharmacology lecture series: Dr. Sayan Chatterjee
INSULIN ADMINISTRATION
Insulin vial with syringe-needle

RED ORANGE
40 units 100 units

Bsc nursing pharmacology lecture series: Dr. Sayan Chatterjee 23

INSULIN ADMINISTRATION(contd)
Insulin pen

24
Bsc nursing pharmacology lecture series: Dr. Sayan Chatterjee
INSULIN ADMINISTRATION(contd)

Bsc nursing pharmacology lecture series: Dr. Sayan Chatterjee 25

SUMMARY
• Type 2 diabetes is recognized as a serious public health concern with a
considerable impact on human life and health expenditures.

• Rapid economic development and urbanization have led to a rising burden of

diabetes in many parts of the world

• India have the maximum increase during the last few years. The prevalence of
type 2 diabetes mellitus is 2.4% in rural population and 11.6% in urban
population. Prevalence of impaired glucose tolerance is also high in the urban
population*

• A variety of oral and injectable drugs including insulin are used for the
management of type 2 diabetes mellitus

• Diet, exercise and a healthy lifestyle aids to reduce hyperglycemia in the initial
stages

*
Source: Ramachandran A. Epidemiology of type 2 diabetes in Indians. J Indian Med Assoc. 2002;100(7):425-427

Bsc nursing pharmacology lecture series: Dr. Sayan Chatterjee 26

Bsc nursing pharmacology lecture series: Dr. Sayan Chatterjee 27