Type Name Example MOA Therapeutic PK/Others Adverse

use effects

Stimulate Insulin Sulfonylureas Glyburide Bind to an ATP-dependent K+ channel on the cell Type 2 diabetes mellitus Highly bound to plasma proteins Hypoglycemia
insulin Secretagogues membrane of pancreatic beta cells. This inhibits a
release tonic, hyperpolarizing efflux of potassium, thus Ineffective in type 1 DM or Metabolised by cytochrome P450 Weight gain
causing the electric potential over the membrane post-pancreatectomy
to become more positive. Voltage-gated Ca2+ Excreted by liver and kidney Secondary resistance (exhaustion of
channels open. Rise in intracellular calcium leads to Hypoglycamic action of sulfonylureas can be inc beta cells)
increased fusion of insulin granulae with the cell due to:
membrane, and therefore increased secretion of CI: Hepatic and renal insufficiency-
(pro)insulin. Displacement from plasma protein(salicylates, inc risk of hypoglycaemia
warfarin), Reduction of hepatic
metabolism(warfarin), Decreasing urinary Pregnancy and lactation- neonatal
excretion(salicylates) hypoglycaemia & teratogenic

Meglitinides Repaglinide Bind to an ATP-dependent K+ channel on the cell Diabetes type 2: taken just Other: Rapid absorption, very fast onset of action, Hypoglycaemia- less than
membrane of pancreatic beta cells. This inhibits a before meal short duration, post-prandial effect, just before sulfonylureas
tonic, hyperpolarizing efflux of potassium, thus meal
causing the electric potential over the membrane Individuals with sulfonylurea Weight gain
to become more positive. Voltage-gated Ca2+
channels open. Rise in intracellular calcium leads to CI: Hepatic and renal insufficiency-
increased fusion of insulin granulae with the cell inc the risk of hypoglycemia
membrane, and therefore increased secretion of
(pro)insulin.

Increase Insulin Biquanides Metformin AMP-activated protein kinase is a major cellular Antihyperglycemic Well absorbed in GIT Diarrhoea and dyspepsia
insulin sensitizers regulator of lipid and glucose metabolism. (‘euglycemic’), doesn’t caue
responsive metformin activates AMPK in hepatocytes; as a hypo even in large doses Not bound to plasma proteins Lactic acidosis (rare but often fatal)
ness result, acetyl-CoA carboxylase activity is reduced,
fatty acid oxidation is induced, and expression of Promotes weight loss in type 2 Not metabolized
lipogenic enzymes is suppressed. diabetics with obesity
Excreted unchanged in urine
Drug choice for type 2 Other: Biguanides reduce pyruvate
diabetics with obesity (newly dehydrogenase activity and mitochondrial
diagnosed type 2 diabetics) transport of reducing agents, and thus enhance
anaerobic metabolism. This subsequent shift to
anaerobic metabolism, in the presence of
reduced insulin, increases production of
precursors for the Krebs cycle. The inhibition of
pyruvate dehydrogenase results in a decreased
ability to channel those precursors into aerobic
metabolism, which, in turn, results in increased
 metabolism of pyruvate to lactate and increases
the net lactic acid production.

CI: Conditions like heart failure, kidney disorders,

lung disease, liver disease which inc risk of lactic
acidosis
Thiazolidinediones Rosiglitazone PPARγ is a member of the steroid hormone nuclear Type 2 DM: highly insulin- Rapidly absorbed. Fluid retention- Enhanced tubular
receptor superfamily resistant patients reabsorption of sodium and water.
Highly protein-bound No effect on renal blood
Activation of PPARγ receptor  migration of drug- flow/filtration.
receptor complex to the DNA  activation Metabolized in the liver.
transcription of genes involved in glucose and fatty Other: Bind to receptors known as “Peroxisome Hepatotoxicity (monitor of liver
acid metabolism Proliferator-Activated Receptor Gamma (PPARγ)” function)

The increased expression of GLUT4 increases the Improve insulin sensitivity. Weight gain- Weight gain is primarily
ability of cells to take up glucose when stimulated due to water retention. Also
by insulin. Change in fat metabolism, including a substantial because it promotes differentiation
reduction in circulating free fatty acids. of preadipocytes into small
adipocytes, apoptosis of large
Redistribution of fat adipocytes. Redistribution of fat
from visceral to subcutaneous
tissue. A disadvantage. Can be
overcome with diet regulation.
Reduced leptin gene expression in
adipocytes  reduced leptin
levels increased appetite

Reduce Alpha- Glucosidase Acarbose Starch blockers (inhibit glucose absorption and Diabetes type 2 in combination Flatulence
intestinal inhibitors decrease postprandial glucose) with other anti-diabetic drugs.
absorption - Competitively inhibit intestinal membrane- - Is taken at the start of Diarrhoea
of carbs bound -glucosidases main meals to have
maximal inhibition of Abdominal pain
glucose absorption.

- Relatively weak
antidiabetic effect.

Increase SGLT inhibitor Dopagliflozin Reducing renal tubular glucose reabsorption, Lower blood sugar in adults Other: Facilitates elimination of glucose through Inc risk for infections in the urinary
glucose (sodium glucose (SGLT2) producing a reduction in blood glucose without with type 2 diabetes the urine. Also eliminates water by osmotic tract
excretion transporter stimulating insulin release. Their action is diuresis, resulting in a lowering of blood glucose
inhibitors) independent od beta cell function and insulin
secretion
Drugs that Drugs acting DPP-4 inhibitors Sitagliptin Upon ingestion of food, GLP-1 is secreted from the Other: GIP: Glucose –dependent insulinotropic Inc beta cells mass and maintains
improve via GLP-1 (Enhances L-cells in the jejunum and ileum. polypeptide beta cells efficiency
incretin the Slows gastric emptying GLP-1: Glucagon like peptide 1
action availability of
endogenous Reduces food intake GLP-1 is derived from proglucagon. It exists in two
GLP-1 equipotent forms, GLP-1(7–36)-NH2 and GLP-1(7–
incretin Suppresses glucagon secretion 37), the former being more abundant.
hormones)
Stimulates insulin secretion T1/2= 1 to 2 mins

In contrast to sulfonylureas, despite

causing increased insulin release
DPP-4 inhibitors do not cause

1. Hypoglycaemia
2. Weight gain
Incretin mimetics Exenatide GLP-1 receptors are expressed in pancreatic islet Other: Exendin-4 was isolated from the salivary Inc risk of pancreatitis
(Acts as and exocrine duct cells and it is postulated that secretions of the Gila monster
agonist at stimulation of these receptors by incretin therapies
GLP-1 may lead to overgrowth of the cells that cover the
receptors) smaller ducts, resulting in hyperplasia, and chronic
low-grade or acute inflammation, potentially
causing acute pancreatitis. May inc beta cell
growth

GLP-1 analog

Inc insulin secretion

Slows gastric emptying

May dec food intake

Amylin analog Pramlinitide Co-secreted with insulin from beta cells As an adjunct to mealtime Other: Compliments the action of insulin Nausea
insuli therapy in patients with
Prolongs gastric emptying time. type 1 or type 2 diabetes Anorexia

Reduces postprandial glucagon secretion. Subcutaneous injection Vomiting

immediately before major
Reduces food intake (centrally mediated appetite meals
suppression)