W14 Diabetes Drugs Flashcards
What are the 10 classes of diabetes medication
Biguanides Alpha-glucosidase inhibitors Sulfonylureas SGLT2 inhibitors Insulin meglitinides Thiazolidinediones Dipeptidyl peptidase-4 (DPP-4) inhibitors GLP-1 receptor agonists Weight loss agents
What are the actions of insulin on the liver ?
Increase glycogen synthesis
Decrease gluconeogenesis
Increase lipogenesis
What promotes the transport of GLUT4 ?
Insulin
Exercise
When is basal insulin used ?
Between meals and overnight
What are some short acting insulin analogues ?
Lispro
Aspart
Glulisine
What are some examples of long acting insulin analogues?
Glargine
Detemir
Degludec
What type of insulin is insulin glargine ?
Basal
What type of insulin is insulin glargine U300?
Basal
What type of insulin is insulin detemir ?
Basal
What type of insulin is insulin degludec ?
Basal
What type of insulin is regular human insulin and what are some examples ?
bolus
Humulin R
Novolin Toronto
What type of insulin are analogue rapid insulins and what are some examples ?
Bolus
Aspart (novorapid)
Lispro (humalog)
Glulisine (apidra)
What type of insulin are analogue ultra-rapid insulins and what are some examples?
Bolus
Ultra rapid aspart (FiAsp)
What is the primary site of action of biguanide ?
Liver
- decrease glucose output
- decrease insulin resistance
What is the primary site of action of sulfonylureas/meglitinides ?
Pancreas
- increase insulin secretion
What is the primary site of action of thiazolidinediones ?
Liver, stomach, adipocytes (?)
- decrease insulin secretion
What is the primary site of actions of DPP-4i, GLP-1 RAs
Pancreas, stomach, liver
- increase insulin secretion
- decrease glucose output
- decrease gastric emptying
What is the primary site of action of SGLT2 inhibitors ?
Kidneys
- increase urinary glucose excretion
What is the primary site of action of a-glucosidase inhibitors ?
Intestines
- decrease carb breakdown and absorption
What class of diabetes medication does metformin belong to?
Biguanide
What are some examples of sulfonylureas ?
Glyburide
Gliclazide
Glimepiride
What is the mechanism of action of metformin?
Liver:
Decrease gluconeogenesis, glycogenolysis, fatty acid oxidation
Intestines:
- increase anaerobic glucose metabolism
Skeletal muscle:
- decrease glucose uptake, glycogenolysis, fatty acid oxidation
Anti-oxidant properties on endothelial cells
Advantages of metformin
Glucose lowering
Durable effect
No weight gain, CV side effects, hypoglycaemia
Side effects of metformin
GI side effects (start low, go slow)
Rare lactic acidosis
Metformin dose
250-500 mg BID
Maximum 1000 mg BID or 2500 mg in divided doses
Examples of short acting secretogogues
Repaglinide
Nateglinide
Mechanism of action of sulfonylureas
Block K(ATP) channel —> stimulate insulin secretion
Advantages of sulfonylureas ?
Inexpensive
Easy to administer
Effective glucose lowering
Disadvantages of sulfonylureas ?
Weight gain
Hypoglycaemia
Durability ?
Effects beta cell function ?
Examples of DPP-4 inhibitors
Alogliptin
Linagliptin
Saxagliptin
Sitagliptan
Examples of short acting GLP-1 receptor agonists
Exenatide
Lixisenatide
Liraglutide
Long acting GLP-1 RAs
Exenatide LAR
Dulaglutide
Semaglutide
Mechanism of action of incretins
- reduce gastric emptying
- reduce appetite
- increase insulin secretion
- decrease glucagon secretion
- decrease hepatic glucose output
Advantages of DPP-4 inhibitors
Glucose lowering
No weight gain
Advantages of GLP-1 RAs
Possible weight loss
Glucose lowering
CV benefit
Disadvantages of GLP-1 RAs ?
Cost/coverage
Injectable
Nausea
Cholelithiasis
Disadvantages of DPP-4 inhibitors
Cost/coverage
Nasal stuffiness
Increased risk of heart failure (saxagliptin)
Examples of SGLT2 inhibitors
Canagliflozin
Dapagliflozin
Empagliflozin
Ertugiflozin
Mechanism of action of SGLT2 inhibitors
Urinary glucose excretion
Advantages of SGLT2 inhibitors
Easy to administer Effective glucose lowering Weight loss Lowers BP Low risk of hypoglycaemia CV benefit in high risk patients
Disadvantages of SGLT2 inhibitors
Polyuria Volume depletion Hyperkalemia Orthostatic hypotension Yeast infections Euglycemic DKA Increase risk of amputation (canagliflozin)
Mechanism of action of thiazolidinediones (TZDs)
- reduce insulin resistance
- modifies adipocyte differentiation
- inhibits VEGF-induced angiogenesis
- reduces lepton levels —> reduced appetite
Advantages of TZDs?
Easy to administer
Effective glucose lowering
Durable
Disadvantages of TZDs
Cost/coverage Weight gain Edema Worsening CHF Distal bone fractures
Examples of TZDs
Pioglitazone
Rosiglitazone
Example of a-glucosidase inhibitor
Acarbose
Mechanism of action of a-glucosidase inhibitors
Inhibits breakdown of non-absorbable complex poly-saccharides
Reduces mono-saccharide absorption
Advantages of a-glucosidase inhibitors
Not systemically absorbed
Targets post prandial glucose
Disadvantages of a-glucosidase inhibitors
Modest A1C lowering
GI side effects (gas, bloating, flatulence)
Multiple daily dosing
What is first line treatment for T2D?
Metformin
What are the A1C target guidelines ?
Adults, T2D, low risk of hypoglycaemia: <6.5%
Most adults, T1D or T2D: <7%
Frail elderly, limited life expectancy, recurrent hypoglycaemia: 7.1-8.5%
When after diagnosis should A1C target be reached?
3-6 months
Initial therapy choice if A1C <1.5% over target
Heathy behaviour, start metformin if not at target in 3 months
Or
Metformin + healthy behaviour
Initial therapy if A1C>1.5% over target
Metformin + healthy behaviour
And
Consider second concurrent agent
When should initial therapy for T2D include insulin +/- metformin?
Symptomatic
Hyperglycaemia
And/or
Metabolic decompensation
