Table 1.
Currently available anti-hyperglycaemic agents
| Agent | Mechanism of action | Advantages | Disadvantages | Adjustment in renal allograft dysfunctiona |
|---|---|---|---|---|
| Biguanides (metformin) | Insulin sensitizing | Efficacy (micro and macrovascular end points), no hypoglycaemia, no weight gain, drug cost | Gastrointestinal side effects, risk of lactic acidosis in renal impairment | eGFR 30–45 mL/min (caution)b |
| eGFR < 30 mL/min (avoid)b | ||||
| Sulphonylureas (glipizide, gliclazide, etc.) | Stimulation of insulin secretion | Efficacy (microvascular end points), drug cost | Hypoglycaemia, weight gain, accumulates in renal failure | ⇓ dose |
| Thiazolidinediones (rosiglitzazone, pioglitazone) | Insulin sensitizing | More sustained glucosecontrol | Weight gain, oedema, drug cost, adverse cardiovascular effects, fracture risk, risk of bladder cancer | Nonspecific |
| Meglitinides (repaglinide1, nateglinide2) | Stimulation of insulin secretion | Reduces postprandial hyperglycaemia, safe with advancing renal failure1 | Hypoglycaemia, weight gain, drug cost, dose adjustment in renal failure2 | Nonspecific |
| Alpha glucosidase inhibitors (acarbose) | Decreases gastrointestinal carbohydrate absorption | No hypoglycaemia, weight neutral | Gastrointestinal side effects | eGFR < 25 mL/min (avoid) |
| GLP-1 agonists (exenatide3, liraglutide4) | Stimulates insulin secretion, decreases glucagon production, stimulates satiety | No weight gain (possible reduction), low risk of hypoglycaemia, lowers blood pressure | Gastrointestinal side effects, risk of pancreatitis altered drug absorption, drug cost, renal impairment, antibody production3 | eGFR3 30–50 mL/min (use with caution) |
| eGFR3 < 30 mL/min (avoid) | ||||
| eGFR4 < 60 mL/min (avoid) | ||||
| DPP-4 inhibitors (sitagliptin5, vildagliptin6, linagliptin6, saxagliptin7) | Decreases inactivation of incretins (GLP-1) | No weight gain | Drug cost, risk of pancreatitis, putative link to certain cancers | 5eGFR < 50 mL/min (avoid) |
| 6No dose adjustment required | ||||
| 7⇓ dose | ||||
| Insulin | Exogenous administration of primary glycaemia countering hormone | Efficacy (micro and macrovascular end points), no ceiling of treatment, range of insulin types for individualization | Weight gain, subcutaneous administration, hypoglycaemia, putative link to certain cancers | Often ⇓ requirement |
GLP-1 = glucagon-like peptide 1, DPP-4 = dipeptidase-4, CNI = calcineurin inhibitor, eGFR = estimated glomerular filtration rate.
aAdapted from British National Formulary (www.bnf.org).
bThese cut-off values may not apply outside the UK.