Type 2 diabetes mellitus

Question 1

First-line treatment (esp. if obese):

Answer 1

–diet therapy

–exercise program (aim for 20–30 mins/d)

Most symptoms improve dramatically within 1–4 wks on diet and exercise alone.

Question 2

If unsatisfactory control persists after 3–6 mths, consider?

Answer 2

adding one of the oral hypoglycaemic agents

• usually starting with metformin.

These agents include:

1. insulin secretogagues such as sulfonylureas
2. glitinides, which increase insulin production
3. insulin sensiters such as metformin and the glitazones, which reduce insulin resistance.

If glycaemic targets are not achieved on monotherapy, common practice is to

• combine one from each class according to the step-up approach
• e.g. metformin plus a sulfonylurea.

Question 3

Commonly prescribed oral hypoglycaemic agents

(with examples)

Answer 3

Drug Duration of action (h) Daily dose range

Sulfonylureas

1. Gliclazide 12–24 40–320 mg
2. Glipizide 6–12 2.5–20 mg
3. Glibenclamide 12–24 2.5–40 mg

• Hypoglycaemia most common side-effect
• Strong and equipotent, caution in elderly

4. Glimepinde >24hr 1–4 mg

• Potent—unsuitable first-line therapy in elderly

Biguanides Metformin 8–12 hr 1 g, tds or 850 mg bd

• Usually reserved for obese but now first line

Side-effects:

• GIT disturbances, esp. diarrhoea
• Avoid in cardiac, renal and hepatic disease
• Lactic acidosis a serious complication

α-glucosidase inhibitor Acarbose 3h 150–600 mg

• Flatulence, liver effects

Thiazolidinediones (glitazones)

1. Pioglitazone 24hr 15–45 mg
   * Caution with heart failure
2. Rosiglitazone 24hr 2–8 mg

• Oedema, weight gains
• Oedema, hepatic effects

Gliptins (DPP-4 inhibitors)

1. Sitagliptin >24hr 25–100 mg
   * Nasopharyngitis, hypersensitivity allergic reactions
2. Vildagliptin >24hr 50–100 mg

SGLT2 inhibitors

1. Canagliflozin 24hr 100–300 mg
   * Genitourinary infections
2. Dapagliflozin 24hr 5–10 mg
   * Dehydration, dizziness, hypoglycaemia

Question 4

Step-up approach to management of type 2 diabetes

Answer 4

When oral hypoglycaemics fail (secondary failure), add:

• an injectable agent (insulin or GLP-1 agonist)

Insulin may eventually be required in many.