Incretin mimetics are a newer class of antidiabetic drugs that work by enhancing the body’s natural incretin hormones. These hormones regulate insulin secretion, reduce glucagon levels, slow gastric emptying, and promote satiety — all of which help lower blood glucose.
Unlike older oral antidiabetic drugs, incretin-based therapies often promote weight loss and have a low risk of hypoglycemia when used alone, making them attractive options in modern diabetes care.
How Incretin Mimetics Work – Mechanism of Action
Incretin Hormones
Incretins are gut-derived hormones released after eating. The two main incretins are:
- GLP-1 (Glucagon-like peptide-1)
- GIP (Glucose-dependent insulinotropic polypeptide)
They:
- Enhance insulin secretion in a glucose-dependent manner.
- Suppress glucagon secretion.
- Delay gastric emptying, slowing carbohydrate absorption.
- Increase satiety, reducing calorie intake.
Two Main Incretin-Based Drug Types
1. GLP-1 Receptor Agonists (Injectables) – e.g., Exenatide (Byetta), Liraglutide (Victoza)
- Mimic the action of GLP-1.
- Promote insulin release and slow gastric emptying.
- Associated with weight loss.
- Inhibit dipeptidyl peptidase-4 (DPP-4), the enzyme that breaks down incretins.
- Prolong the activity of endogenous incretins.
Indications
- Type 2 diabetes mellitus inadequately controlled with diet and exercise alone.
- May be used in combination with metformin, sulfonylureas, thiazolidinediones, or insulin.
- Particularly useful in overweight patients who may benefit from weight reduction.
Contraindications & Cautions
- Type 1 diabetes mellitus (ineffective).
- Diabetic ketoacidosis (DKA).
- Severe kidney disease (dose adjustments may be needed).
- Pregnancy – safety not established.
- History of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (for some GLP-1 agonists).
Drug Interactions
- Increased hypoglycemia risk when combined with insulin or sulfonylureas (may require dose adjustment of the latter).
- May slightly increase serum digoxin levels – monitor if co-administered.
Adverse Effects
Common
- Nausea, vomiting, upset stomach.
- Diarrhea or constipation.
- Weight loss.
- Loss of appetite.
- Heartburn, dizziness, headache.
Serious
- Pancreatitis – warning signs include persistent abdominal pain (possibly radiating to the back), nausea, and vomiting.
- Hypersensitivity reactions – rash, hives, facial swelling.
Nursing Management & Patient Education
Monitor for signs of hypoglycemia, especially if used with insulin or sulfonylureas.
Observe for symptoms of pancreatitis; discontinue immediately if suspected.Monitor for allergic skin reactions.
Advise patients to:
- Take Sitagliptin exactly as prescribed, once daily.
- Inject Exenatide within 1 hour before meals.
- Use Liraglutide once daily, with or without food.
Encourage regular blood glucose monitoring.
Educate on healthy diet and exercise as part of therapy.
Dosage & Routes – Quick Reference Table
| Generic | Trade Name | Indication | Safe Dose & Route |
|---|---|---|---|
| Sitagliptin | Januvia | Type 2 DM | 100 mg orally daily |
| Exenatide | Byetta | Type 2 DM | 5–10 mcg subcut within 1 hr of a meal |
| Liraglutide | Victoza | Type 2 DM | 0.6–1.2 mg subcut daily |
Summary Table – GLP-1 vs DPP-4 Inhibitors
| Feature | GLP-1 Receptor Agonists | DPP-4 Inhibitors |
|---|---|---|
| Administration | Injectable | Oral |
| Weight Effect | Loss | Neutral |
| Hypoglycemia Risk | Low (monotherapy) | Low |
| GI Side Effects | Common | Rare |
| Example | Exenatide, Liraglutide | Sitagliptin |
FAQs
1. Can incretin mimetics cause low blood sugar?
Rare when used alone, but risk increases when combined with insulin or sulfonylureas.
2. Do these drugs help with weight loss?
GLP-1 agonists often promote weight loss; DPP-4 inhibitors are weight-neutral.
3. How soon do they work?
Blood glucose improvements can be seen within days, but full effects may take weeks.
4. Can I take them if I have kidney problems?
Some require dose adjustments; Exenatide is not recommended in severe renal impairment.
5. Are they safe in pregnancy?
Safety is not established; insulin is preferred during pregnancy.
