Introduction
Diabetes mellitus is a chronic metabolic disorder caused by reduced insulin secretion, reduced insulin action, or both. Insulin is essential for glucose uptake, fat storage and protein synthesis. Lack of insulin leads to hyperglycemia. Management includes insulin therapy and oral hypoglycemic agents (OHAs). Treatment choice depends on the type of diabetes, severity, age and comorbid conditions.
Insulin
Insulin is a peptide hormone released from pancreatic β-cells. It lowers blood glucose by promoting glucose uptake in muscle and fat, increasing glycogen synthesis and reducing gluconeogenesis.
Classification of Insulin (Based on Duration)
- Rapid-acting: Insulin lispro, aspart, glulisine
- Short-acting: Regular insulin
- Intermediate-acting: NPH insulin
- Long-acting: Glargine, detemir, degludec
- Premixed: 30/70 or 50/50 combinations
Insulin Preparations
- Human insulin: Regular, NPH
- Analogue insulin: Lispro, Aspart, Glargine, Detemir
- Inhalational insulin: Limited use
Therapeutic Uses
- Type 1 diabetes
- Type 2 diabetes not controlled with OHA
- Diabetic ketoacidosis
- Hyperosmolar hyperglycemic state
- Gestational diabetes
- Hyperkalemia (along with glucose)
Adverse Effects
- Hypoglycemia (sweating, tremors, confusion, coma)
- Weight gain
- Local reactions and lipodystrophy
- Rare: insulin allergy
Insulin Analogues
Insulin analogues are modified forms of insulin designed to produce faster or prolonged action with predictable absorption.
Rapid-Acting Analogues
- Insulin lispro
- Insulin aspart
- Insulin glulisine
Onset within minutes, ideal for post-meal glucose control. Lower risk of late hypoglycemia.
Long-Acting Analogues
- Insulin glargine: Basal insulin for 24 hours
- Insulin detemir: Duration up to 24 hours
- Insulin degludec: Ultra-long action (up to 42 hours)
Oral Hypoglycemic Agents (OHAs)
OHAs are used mainly in type 2 diabetes. They lower blood sugar through different mechanisms such as increasing insulin secretion, reducing hepatic glucose production or improving insulin sensitivity.
1. Sulfonylureas
Increase insulin release from β-cells by closing K-ATP channels.
- First generation: Tolbutamide, Chlorpropamide
- Second generation: Glipizide, Glibenclamide, Glimepiride
Adverse effects: Hypoglycemia, weight gain.
2. Meglitinides (Glinides)
Short-acting insulin secretagogues.
- Repaglinide
- Nateglinide
Good for controlling post-meal glucose spikes.
3. Biguanides
Drug of choice: Metformin
- Reduces hepatic glucose output
- Improves insulin sensitivity
- Does NOT cause hypoglycemia
Adverse effects: GI discomfort; rare lactic acidosis.
4. Thiazolidinediones (Glitazones)
Improve insulin sensitivity by activating PPAR-γ receptors.
- Pioglitazone
- Rosiglitazone
Side effects: Weight gain, edema, heart failure risk.
5. α-Glucosidase Inhibitors
Delay absorption of carbohydrates in the intestine.
- Acarbose
- Voglibose
Side effects: Flatulence, diarrhea.
6. DPP-4 Inhibitors (Gliptins)
Enhance incretin hormones → increase insulin release and reduce glucagon.
- Sitagliptin
- Vildagliptin
- Linagliptin
- Saxagliptin
Weight-neutral and low risk of hypoglycemia.
7. GLP-1 Receptor Agonists (Incretin Mimetics)
Injectable agents that increase insulin secretion and slow gastric emptying.
- Exenatide
- Liraglutide
Benefits: Weight loss, low hypoglycemia risk.
8. SGLT2 Inhibitors
Increase glucose excretion through urine by blocking renal reabsorption.
- Canagliflozin
- Dapagliflozin
- Empagliflozin
Benefits: Weight loss, BP reduction.
Risks: Genitourinary infections, dehydration.
9. Amylin Analogues
- Pramlintide
Injected before meals; delays gastric emptying and reduces post-meal glucose rise.
Combination Therapy
Many patients require combinations such as:
- Metformin + Sulfonylurea
- Metformin + DPP-4 inhibitor
- Metformin + SGLT2 inhibitor
Goal is to target multiple mechanisms for better glycemic control.
Detailed Notes:
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