Insulin therapy is indispensable for type 1 diabetes and may be required in advanced type 2 diabetes.
Physiology:
Produced by β-cells of the pancreas; released in response to increased blood glucose.
Lowers blood glucose by facilitating glucose uptake in muscle and adipose tissue and by inhibiting hepatic glucose production.
Types of Insulin:
Rapid-Acting (e.g., insulin lispro, aspart):
Onset: ~15 minutes.
Peak: 1 hour.
Duration: 2-4 hours.
Short-Acting (e.g., regular insulin):
Onset: ~30 minutes.
Peak: 2-3 hours.
Duration: 3-6 hours.
Intermediate-Acting (e.g., NPH insulin):
Onset: 1-2 hours.
Peak: 4-12 hours.
Duration: 12-18 hours.
Long-Acting (e.g., insulin glargine, detemir):
Onset: 1-2 hours.
Peak: Minimal or none.
Duration: Up to 24 hours.
Clinical Use:
Type 1 Diabetes: Basal and bolus insulin regimens.
Type 2 Diabetes: As insulin resistance progresses, insulin may be added to oral agents.
Hyperkalemia: Insulin (with glucose) shifts potassium intracellularly.
Side Effects:
Hypoglycemia, weight gain, lipodystrophy at injection sites.
Oral Hypoglycemic (Antidiabetic) Agents
These agents are primarily used in type 2 diabetes to enhance insulin secretion, improve insulin sensitivity, or reduce glucose production.
1) Sulfonylureas (e.g., glipizide, glyburide):
Mechanism: Stimulate pancreatic β-cells to release insulin.
Use: First-line therapy in type 2 diabetes.
Side Effects: Hypoglycemia, weight gain.
2) Biguanides (e.g., metformin):
Mechanism: Decrease hepatic gluconeogenesis and improve insulin sensitivity.
Use: First-line treatment for type 2 diabetes.
Side Effects: Gastrointestinal upset, lactic acidosis (rare).
3) Thiazolidinediones (e.g., pioglitazone, rosiglitazone):
Mechanism: Activate PPAR-γ receptors to improve insulin sensitivity.
Use: Adjunct therapy in type 2 diabetes.
Side Effects: Weight gain, edema, risk of heart failure, bone fractures.
4) DPP-4 Inhibitors (e.g., sitagliptin, saxagliptin):
Mechanism: Inhibit dipeptidyl peptidase-4, prolonging incretin hormones which increase insulin secretion and decrease glucagon.
Use: Type 2 diabetes.
Side Effects: Nasopharyngitis, pancreatitis (rare).
5) SGLT2 Inhibitors (e.g., canagliflozin, dapagliflozin):
Mechanism: Inhibit sodium-glucose co-transporter 2 in the kidneys, promoting glucose excretion.
Use: Type 2 diabetes, reducing cardiovascular risk.
Side Effects: Genital infections, urinary tract infections, dehydration.
6) GLP-1 Receptor Agonists (e.g., exenatide, liraglutide):
Mechanism: Mimic glucagon-like peptide-1, enhancing insulin secretion and suppressing glucagon.
Use: Type 2 diabetes, weight management.
Side Effects: Gastrointestinal disturbances, risk of pancreatitis.