Antidiabetic drugs: oral drugs and incretin mimetics - Quick Reference

This is a Quick Reference article. See also the main article Oral antidiabetic drugs and GLP-1 analogues in the treatment of type 2 diabetes .

Metformin

• The drug of choice
• Initially 500 mg in the morning, increased by 500 mg at weekly intervals. The slow dose increase may improve tolerance. Max. dose 3 g daily, divided into 2–3 doses.
• Does not cause hypoglycaemia.
• Contraindicated in significant renal impairment (GFR under 60 ml/min)
• Available as a combination product with pioglitazone (Competact^®), sitagliptin (Janumet^®, Velmetia^®) and vildagliptin (Eucreas^®)

Sulphonylureas

• Agents
  • Glibenclamide 3.5–14 mg daily; doses over 7 mg daily must be divided into two doses
  • Glimepiride 1–6 mg daily; usually administered once daily
  • Glipizide 2.5–30 mg daily; doses over 15 mg daily must be divided into two doses
• May cause hypoglycaemia as they augment insulin secretion regardless of blood glucose concentration.
• Initially the dose may be small, but it should be rapidly increased.
• Not recommended as monotherapy for first-line treatment unless particularly indicated
  • If treatment has continued long and is problem free, there is no need to change medication.
• Can be combined with metformin and insulin.

Meglitinides (glinides)

• Agents
  • Nateglinide (Starlix^®) 60–180 mg/meal, max. 540 mg daily
  • Repaglinide (Novonorm^® and generic preparations) 0.5–4 mg/meal, max. 16 mg daily
• Administered with meals
  • Rapid onset of action in less than 30 minutes with variable duration of activity, typically less than 3 hours
  • Action is dose dependent requiring estimation of dietary carbohydrate content.
  • As with mealtime insulin, dose should be varied according to amount of dietary carbohydrate.
• Particularly suitable for patients with high postprandial blood glucose but only slightly elevated fasting blood glucose
• Despite the short duration of activity may cause significant hypoglycaemia.
• Can be combined with metformin.

DPP-4 inhibitors (gliptins)

• Agents
  • Sitagliptin (Januvia^®) 100 mg once daily
  • Vildagliptin (Galvus^®) 100 mg daily divided into two doses (when combined with a sulphonylurea, 50 mg daily in the morning)
  • Saxagliptin (Onglyza^®) 5 mg once daily
  • Linagliptin (Trajenta^®) 5 mg once daily
• Stimulate glucose-dependent insulin secretion and can therefore be used to manage postprandial hyperglycaemia.
• Can be combined with all other oral antidiabetic drugs.
• Sitagliptin and vildagliptin are also marketed as combination products with metformin (for trade names, see above).

Incretin mimetics (GLP-1 receptor agonists)

• Agents
  • Exenatide by injection (Byetta^®) initially 5 micrograms twice daily, increased if necessary after 1 month to 10 micrograms twice daily
  • Liraglutide by injection (Victoza^®) initially 0.6 mg once daily, increased if necessary after at least 1 week to 1.2 mg once daily
  • Exenatide for once-weekly injection (Bydureon^®; produced by utilizing microparticle technology): 2 mg once weekly s.c.
• Stimulate glucose-dependent insulin secretion and can therefore be used to manage postprandial hyperglycaemia.
• Promote significant weight loss.
• The most common adverse effect is nausea particularly at start of treatment, which can be considerably reduced by increasing the dose slowly to the maintenance dose.

Glitazones (insulin sensitisers)

• Agents
  • Pioglitazone (Actos^®) initially 15 or 30 mg once daily, increased if necessary to 45 mg once daily.
  • Rosiglitazone has been withdrawn from the European market.
• Hypoglycaemic effect is slow to develop and efficacy of treatment should be assessed after 3–6 months.
• Either as monotherapy or combined with metformin or a sulphonylurea
• Adverse effects: worsening of fluid retention and heart failure, increased fracture risk in women, anaemia, worsening ocular symptoms in Basedow’s disease and macular oedema

Glucose reuptake inhibitors (dapagliflozin)

• Agents
• Dapagliflozin (Forxiga^®): normal initiation and maintenance dose 10 mg/day, in liver failure 5 mg/day
• The drug is not recommended in moderate renal failure nor in severe liver failure.
• Can be combined with other antidiabetic drugs, also with insulin in type 2 diabetics.
• Increases the occurrence of urinary tract and genital infections (e.g. vulvovaginitis, balanitis). The drug must be discontinued if the patient develops pyelonephritis or urosepsis.