Drugs for Diabetes Mellitus Type II
Drug name MOA Therapeutic uses AE/ Contraindication
Glyburide • are used in diabetes mellitus type 2 Adverse effects
(Sulfonylureas) • are ineffective in type 1 diabetes or o Hypoglycemia
post-pancreatectomy (pancreatic o Weight gain
beta cells are destructed) o Secondary resistance (exhaustion of beta cells)
Insulin secretagogeus
Block ATP-sensitive potassium channels of the Contraindications
pancreatic β cells → depolarization of the cell o Hepatic and renal insufficiency
o increase the risk of hypoglycemia
membrane → calcium influx → insulin
o Pregnancy and lactation
secretion
o Neonatal hypoglycemia
Extrapancreatic effect:
o Teratogenic
↓ hepatic gluconeogenesis, ↑ peripheral
Repaglinide o Diabetes type 2: taken just before Adverse effects
(Meglitinides) insulin sensitivity each meal o Hypoglycemia: (less than sulfonylureas)
o Individuals with sulfonylurea allergy o Weight gain
Contraindications
o Hepatic and renal insufficiency
o increased the risk of hypoglycemia
Metformin Impairs mitochondrial respiration→ reduced • Antihyperglycemic ("euglycemic"), Adverse effects
(Biguanides) ATP generation and AMP accumulation→ does not cause hypoglycemia even in • Diarrhea and dyspepsia (up to 30% of
activation of AMP kinase → changes large doses! patients)
expression of genes that facilitate • Promotes weight loss in type 2 • Lactic acidosis (rare but often fatal) (reduce
↑ insulin sensitivity diabetics with obesity pyruvate dehydrogenase activity→ promotes
↓ hepatic output of glucose • drug of choice for type 2 diabetics anaerobic metabolism-> increase conversion
Insulin Sensitizers
↑ glucose uptake by skeletal muscles with obesity (newly diagnosed type 2 of pyruvate to lactate)
↑ fatty acid uptake and oxidation diabetics) Contraindication
↓ intestinal absorption of glucose conditions that can increase the risk of lactic
acidosis: heart failure, kidney disorders,lung
disease , liver disease
Rosiglitazone Bind to receptors known as “Peroxisome Diabetes mellitus type II: highly insulin- Adverse effects
(Thiazolidinediones) Proliferator-Activated Receptor Gamma resistant patients. • Fluid retention
(PPARγ)”→ Activation of PPARγ receptor → • Hepatotoxicity (monitoring of liver function)
migration of drug-receptor complex to the DNA • Weight gain (water retention)
→ activation transcription of genes involved in Contraindication
glucose and fatty acid metabolism (especially • Heart failure, Pregnancy, Hepatic failure
glucose transporter GLUT4)
JCXB
, • Improve insulin sensitivity
• Change in fat metabolism, including a
substantial reduction in circulating free
fatty acids.
• Redistribution of fat
Acarbose • Starch blockers (inhibit glucose absorption Diabetes type 2 in combination with Adverse effects
(Alpha-Glucosidase and decrease postprandial glucose) other anti-diabetic drugs. ▪ Flatulence
Inhibitors) • Competitively inhibit intestinal membrane- ▪ Is taken at the start of main meals to ▪ Diarrhea
bound -glucosidases have maximal inhibition of glucose ▪ Abdominal pain
absorption.
▪ Relatively weak antidiabetic effect.
Dapagliflozin • reversible inhibition of SGLT-2 in the Adverse effects:
(SGLT inhibitor) proximal tubule of the kidney → ↓ glucose • Increased risk for infections in the urinary
Increase glucose reabsorption in the proximal convoluted tract
excretion tubule of the kidney → glycosuria and
polyuria
• It additionally eliminates water by osmotic
diuresis, resulting in a lowering of blood
pressure.
Sitagliptin indirectly increase the endogenous incretin Do not cause hypoglycemia and weight gain
(DPP-4 Inhibitors) effect by inhibiting the DPP-4 that breaks down
GLP-1 → ↑ insulin secretion, ↓ glucagon
secretion, delayed gastric emptying
Exenatide • GLP-1 analog
(Incretin mimetics) • Increases insulin secretion
• Slows gastric emptying
• May decrease food intake
• Increased risk of pancreatitis
Pramlintide • Amilinomimetics • As an adjunct to mealtime insulin Adverse effects
(Amylin analog) • Delays gastric emptying therapy in patients with type 1 or • Nausea
• Decrease postprandial glucagon secretion type 2 diabetes • Anorexia
• Improves satiety • S.c. injection immediately before • Vomiting
major meals
JCXB
, Drugs for Diabetes Mellitus Type I
Insulin MOA: binds to insulin receptor→ dimerization and phosphorylation of tyrosine kinase enzyme→ activation of transcription factors→ increase GLUT4 of cell
membrane→ increase glucose uptake by cells
Drug name Type of Onset of Peak of Duration of Description
insulin action action action
Lispro Insulin ▪ Bolus insulin
10~15mins 30~90mins 3~5 hrs
(Rapid acting) analogues ▪ Administered subcutaneously or intravenously (in emergencies).
Humulin R Human ▪ Rapidly lower blood glucose.
(short-acting) insulin ▪ Administered usually 3 times a day 20-30 minutes prior to each meal
30~60mins 1~4 hrs 4~8hrs
(short-acting) or just prior to a meal (rapid-acting).
Isophane (NPH) Human ▪ Basal insulin
(intermediate insulin 1~3hrs 4~8hrs 12~18hrs ▪ Subcutaneously only.
acting) ▪ Once or twice daily:
Ultralene Human • Morning or bedtime - long-acting insulins
Humulin (Zinc) insulin • Morning + bedtime - intermediate-acting insulins
(Long-acting)
Glargine Insulin 4~8hrs 8~12hrs 24~36hrs
(Long-acting) analogues Glargine: precipitates at the injection site (less soluble at injection site) and has
slower onset and prolonged effect (has no peak plasma concentration).
Insulin adverse effects
• Hypoglycemia
o After insulin injection--> hot both--> vasodilation--> more rapid absorption of insulin--> rapid decrease of blood glucose
• Lipodystrophy at injection sites
o Repeated insulin injections at the same spot.
o Atrophy of subcutaneous fatty tissue at the site of injection due to local immune reaction.
• Allergy
• Insulin resistance
o Insulin may cause anti-insulin antibodies production that neutralize the action of insulin and leads to insulin resistance.
o Prevention: Use ‘human’ insulins or insulin analogues.
JCXB
Drug name MOA Therapeutic uses AE/ Contraindication
Glyburide • are used in diabetes mellitus type 2 Adverse effects
(Sulfonylureas) • are ineffective in type 1 diabetes or o Hypoglycemia
post-pancreatectomy (pancreatic o Weight gain
beta cells are destructed) o Secondary resistance (exhaustion of beta cells)
Insulin secretagogeus
Block ATP-sensitive potassium channels of the Contraindications
pancreatic β cells → depolarization of the cell o Hepatic and renal insufficiency
o increase the risk of hypoglycemia
membrane → calcium influx → insulin
o Pregnancy and lactation
secretion
o Neonatal hypoglycemia
Extrapancreatic effect:
o Teratogenic
↓ hepatic gluconeogenesis, ↑ peripheral
Repaglinide o Diabetes type 2: taken just before Adverse effects
(Meglitinides) insulin sensitivity each meal o Hypoglycemia: (less than sulfonylureas)
o Individuals with sulfonylurea allergy o Weight gain
Contraindications
o Hepatic and renal insufficiency
o increased the risk of hypoglycemia
Metformin Impairs mitochondrial respiration→ reduced • Antihyperglycemic ("euglycemic"), Adverse effects
(Biguanides) ATP generation and AMP accumulation→ does not cause hypoglycemia even in • Diarrhea and dyspepsia (up to 30% of
activation of AMP kinase → changes large doses! patients)
expression of genes that facilitate • Promotes weight loss in type 2 • Lactic acidosis (rare but often fatal) (reduce
↑ insulin sensitivity diabetics with obesity pyruvate dehydrogenase activity→ promotes
↓ hepatic output of glucose • drug of choice for type 2 diabetics anaerobic metabolism-> increase conversion
Insulin Sensitizers
↑ glucose uptake by skeletal muscles with obesity (newly diagnosed type 2 of pyruvate to lactate)
↑ fatty acid uptake and oxidation diabetics) Contraindication
↓ intestinal absorption of glucose conditions that can increase the risk of lactic
acidosis: heart failure, kidney disorders,lung
disease , liver disease
Rosiglitazone Bind to receptors known as “Peroxisome Diabetes mellitus type II: highly insulin- Adverse effects
(Thiazolidinediones) Proliferator-Activated Receptor Gamma resistant patients. • Fluid retention
(PPARγ)”→ Activation of PPARγ receptor → • Hepatotoxicity (monitoring of liver function)
migration of drug-receptor complex to the DNA • Weight gain (water retention)
→ activation transcription of genes involved in Contraindication
glucose and fatty acid metabolism (especially • Heart failure, Pregnancy, Hepatic failure
glucose transporter GLUT4)
JCXB
, • Improve insulin sensitivity
• Change in fat metabolism, including a
substantial reduction in circulating free
fatty acids.
• Redistribution of fat
Acarbose • Starch blockers (inhibit glucose absorption Diabetes type 2 in combination with Adverse effects
(Alpha-Glucosidase and decrease postprandial glucose) other anti-diabetic drugs. ▪ Flatulence
Inhibitors) • Competitively inhibit intestinal membrane- ▪ Is taken at the start of main meals to ▪ Diarrhea
bound -glucosidases have maximal inhibition of glucose ▪ Abdominal pain
absorption.
▪ Relatively weak antidiabetic effect.
Dapagliflozin • reversible inhibition of SGLT-2 in the Adverse effects:
(SGLT inhibitor) proximal tubule of the kidney → ↓ glucose • Increased risk for infections in the urinary
Increase glucose reabsorption in the proximal convoluted tract
excretion tubule of the kidney → glycosuria and
polyuria
• It additionally eliminates water by osmotic
diuresis, resulting in a lowering of blood
pressure.
Sitagliptin indirectly increase the endogenous incretin Do not cause hypoglycemia and weight gain
(DPP-4 Inhibitors) effect by inhibiting the DPP-4 that breaks down
GLP-1 → ↑ insulin secretion, ↓ glucagon
secretion, delayed gastric emptying
Exenatide • GLP-1 analog
(Incretin mimetics) • Increases insulin secretion
• Slows gastric emptying
• May decrease food intake
• Increased risk of pancreatitis
Pramlintide • Amilinomimetics • As an adjunct to mealtime insulin Adverse effects
(Amylin analog) • Delays gastric emptying therapy in patients with type 1 or • Nausea
• Decrease postprandial glucagon secretion type 2 diabetes • Anorexia
• Improves satiety • S.c. injection immediately before • Vomiting
major meals
JCXB
, Drugs for Diabetes Mellitus Type I
Insulin MOA: binds to insulin receptor→ dimerization and phosphorylation of tyrosine kinase enzyme→ activation of transcription factors→ increase GLUT4 of cell
membrane→ increase glucose uptake by cells
Drug name Type of Onset of Peak of Duration of Description
insulin action action action
Lispro Insulin ▪ Bolus insulin
10~15mins 30~90mins 3~5 hrs
(Rapid acting) analogues ▪ Administered subcutaneously or intravenously (in emergencies).
Humulin R Human ▪ Rapidly lower blood glucose.
(short-acting) insulin ▪ Administered usually 3 times a day 20-30 minutes prior to each meal
30~60mins 1~4 hrs 4~8hrs
(short-acting) or just prior to a meal (rapid-acting).
Isophane (NPH) Human ▪ Basal insulin
(intermediate insulin 1~3hrs 4~8hrs 12~18hrs ▪ Subcutaneously only.
acting) ▪ Once or twice daily:
Ultralene Human • Morning or bedtime - long-acting insulins
Humulin (Zinc) insulin • Morning + bedtime - intermediate-acting insulins
(Long-acting)
Glargine Insulin 4~8hrs 8~12hrs 24~36hrs
(Long-acting) analogues Glargine: precipitates at the injection site (less soluble at injection site) and has
slower onset and prolonged effect (has no peak plasma concentration).
Insulin adverse effects
• Hypoglycemia
o After insulin injection--> hot both--> vasodilation--> more rapid absorption of insulin--> rapid decrease of blood glucose
• Lipodystrophy at injection sites
o Repeated insulin injections at the same spot.
o Atrophy of subcutaneous fatty tissue at the site of injection due to local immune reaction.
• Allergy
• Insulin resistance
o Insulin may cause anti-insulin antibodies production that neutralize the action of insulin and leads to insulin resistance.
o Prevention: Use ‘human’ insulins or insulin analogues.
JCXB
