Pharmacokinetics of oral antihyperglycaemic agents in patients with renal insufficiency

Clin Pharmacokinet. 1996 Aug;31(2):111-9. doi: 10.2165/00003088-199631020-00003.


This paper reviews the effects of renal insufficiency on the pharmacokinetics of oral antidiabetic drugs. Of the 3 groups of drugs currently available for the treatment of non-insulin-dependent diabetes mellitus (NIDDM), the sulphonylureas and metformin are, in general, well-tolerated and generally safe. In patients with chronic renal insufficiency, however, care must be exercised in the use of many of these drugs, as accumulation, either of the active drug or of active metabolites, can lead to serious adverse effects such as hypoglycaemia or, with metformin, lactic acidosis. The sulphonylurea drugs, to a greater or lesser degree, are metabolised in the liver to a variety of active or inactive compounds which, in general, are excreted by the kidneys. In addition, varying amounts of parent compound may depend on renal elimination. As a result, sulphonylurea drugs such as tolazamide, acetohexamide, chlorpropamide and glibenclamide (glyburide) are more likely to cause significant hypoglycaemia, as the metabolism of these drugs, compared with other commonly prescribed sulphonylureas, can lead to the accumulation of either the parent drug or the active metabolite in the presence of renal insufficiency. Tolbutamide, glipizide, gliclazide and gliquidone are much less likely to cause hypoglycaemia as their metabolites are either inactive or have minimal hypoglycaemic potency. Metformin is dependent on renal excretion and is not significantly metabolised. As a result, caution is required when treating patients with renal insufficiency where metformin accumulation can occur, with the danger of lactic acidosis. Although the correlation between creatinine clearance (CLCR) and total oral clearance of drug is weaker than the correlation between CLCR and renal clearance (CLR) of metformin, it is clear that renal insufficiency is associated with most cases of metformin-induced lactic acidosis. For this reason, clinicians in general would regard a raised plasma creatinine as a contraindication to metformin treatment. Acarbose, an alpha-glucosidase inhibitor, and a relatively new agent for treating NIDDM, is likely to be safe in patients with impaired renal function, as the drug is not significantly absorbed from the gut, but data on this subject are lacking.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Acarbose
  • Administration, Oral
  • Diabetes Mellitus, Type 2 / drug therapy
  • Humans
  • Hypoglycemic Agents / pharmacokinetics*
  • Hypoglycemic Agents / therapeutic use
  • Metformin / pharmacokinetics
  • Metformin / therapeutic use
  • Renal Insufficiency / metabolism*
  • Sulfonylurea Compounds / pharmacokinetics
  • Sulfonylurea Compounds / therapeutic use
  • Trisaccharides / pharmacokinetics
  • Trisaccharides / therapeutic use


  • Hypoglycemic Agents
  • Sulfonylurea Compounds
  • Trisaccharides
  • Metformin
  • Acarbose