Oral hypoglycaemic agents 2020

ORAL
HYPOGLYCAEMIC
AGENTS
Dr. Pravin Prasad
MBBS, MD Clinical Pharmacology
Assistant Professor, Department of Clinical Pharmacology
Maharajgunj Medical Campus
6 July 2020 (22 Asar 2077), Monday

Classification
 Enhance Insulin Secretion
o Sulfonylureas (K+ATP channels blockers)
 First Generation: Chlorpropamide,Tolbutamide
 Second Generation: Glibenclamde (Glyburide), Glipizide,
Gliclazide, Glimepiride
o Meglitinide/phenylalanine analouges:
 Repaglinide, Nateglinide
o Glucagon-like peptide (GLP-1) receptor agaonists (injectable):
 Exenadite, Liraglutide
o Dipeptidyl peptidase-4 (DPP-4) inhibitors:
 Sitagliptin,Vildagliptin, Saxagliptin, Alogliptin, Linagliptin

Classification
 Overcome Insulin Resistance
o Biguanides (AMPK activators):
 Metformin
o Thiazolidinediones (PPARγ activator):
 Pioglitazone
 Miscellaneous
α-Glucosidase inhibitors Acarbose, Miglitol,Voglibose
Amylin analogue Pramlintide
Dopamine D2 receptor agonist Bromocriptine
Sodium Glucose Co-Transport 2 (SGLT 2)
inhibitor
Dapagliflozine

Mechanism of Action: In a nutshell

Sulfonylureas
 Mechanism of action:
o Blocks the K+
ATP channel and reduced influx of K+ ion
o Partial depolarization of pancreatic beta-cells 
o Increased influx of Ca++ ions as well as release of Ca++ from intracellular stores

o Exocytotic release of insulin
 Minor action:
o Reduces glucagon secretion
o Reduced hepatic degradation of insulin
 Extra-pancreatic action:
o Sensitizes the peripheral tissues to the action of insulin
 Seen on prolonged use

Sulfonylureas
 Adverse Effects:
o Hypoglycaemia
o Non specific Side effects (mild and infrequent):
 Weight gain, nausea, vomiting, flatulence, diarrhoea,
paraesthesia
o Hypersensitivity
o SU + alcohol:
 Flushing, disulfiram-like reaction
Should not be used in pregnancy and lactating mothers

Repaglinide and Nateglinide:
 K+ATP channel blockers
 Quick and short lasting action
o Quick absorption and rapid metabolism
 Administered before each major meal
o Normalises meal time glucose levels
o Lower incidence of hypoglycaemia
 S/E: Mild headache, dyspepsia, arthralgia, weight gain
 Indication:
o Type 2 DM with pronounced postprandial hyperglycaemia
o Along with Metformin/long acting insulin
 Avoid in liver disease
Meglitinide/Phenylalanine analogues
(Repaglinide, Nateglinide)

Dipeptidyl peptidase-4 (DPP-4) inhibitors
 Sitagliptin:
o Competitive and selective DPP-4 inhibitor
 Potentiates the action of GLP-1 and GIP
o Body weight neutral, low risk of hypoglycaemia
o Well absorbed orally, little metabolised, largely excreted
unchanged in urine
o Dose reduction needed in renal dysfunction
o S/E: nausea, loose stools, headaches, rashes, allergic
reactions, edema

Biguanides (Metformin, Phenformin)
 Mechanism of Action:
o Activation of AMPK, leading to:
 Suppression of hepatic gluconeogenesis
 Enhances insulin-mediated glucose uptake and disposal in
skeletal muscle and fat
 Interferes with mitochondrial respiratory chain and
promotes peripheral glucose utilization
 Retards glucose absorption of glucose, hexose, amino
acids,Vit B12

 Advantages:
o Non-hypoglycaemic
o Weight loss
o Prevents long term complications
o Prolongs beta cell life

 Adverse Effects:
o Limiting feature: gastro-intestinal intolerance
o Hypoglycaemia in overdose
o Lactic acidosis
o Vitamin B12 deficiency
 Contraindications:
o Hypotensive states
o Heart failure
o Severe respiratory, hepatic and renal disease
o Alcoholics

Thiazolidinediones (PPARγ activator):
Pioglitazone
 Multiple actions:
o Enhances transcription of insulin responsive genes
o Reverses insulin resistance
o Suppresses hepatic gluconeogenesis
 Additional actions: 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

Miscellaneous OHA
 Acarbose:
o Inhibits α-glucosidases enzyme slow down and decrease
digestion and absorption of polysaccharides and sucrose.
o Additionally promotes GLP-1 release
o S/E: Flatulence, abdominal discomfort, loose stool; Poor patient
acceptability
 Pramlintide:
o Synthetic amylin analogue
o Attenuates postprandial glycaemia and exerts centrally mediated
anorectic action
o Reduction in body weight ++

Miscellaneous OHA
 Bromocriptine:
o Dopamine D2 agonist;
o Acts on hypothalamic dopaminergic control of the circadian
rhythm of hormone (GH, prolactin, ACTH) release and reset
it to reduce insulin resistance.
Dapagliflozin:
o SGLT-2 inhibitor  glycosuria
o Prone to cause urinary tract infection

Glucagon
 An Hyperglycaemic agent
 Polypeptide chain, released as prohormone from alpha cells of
pancreas
 Acts by:
o Binds to glucagon receptor  stimulates cells
 Liver: increased glycogenolysis, gluconeogenesis
 Muscle, fat cells: decreased glucose utilization
 Heart: increased force and rate of contraction
 Uses: Hypoglycaemia,Cardiogenic shock

Oral hypoglycaemic agents 2020