What diabetic drug class to use when kidney impaired?

Recent guidelines for the treatment of diabetes (ADA, EASD 2012) propose personalization of glycaemic goals. For the majority of diabetic patients the appropriate goal is a haemoglobin A1c (HbA1c) < 7% but for patients with severe comorbidities a goal between 7% and 8% is acceptable. Diabetic subjects with CKD usually belong to this group.

The glycated HbA1c is the most popular and well-accepted biological marker for the assessment of long-term glycaemic control. This also applies to patients with diabetes and renal disease. However, the method has significant limitations in these patients. The measurement is influenced by both renal function and complications of chronic kidney disease such as haemolysis, iron deficiency and metabolic acidosis.

In most cases diabetic subjects with chronic kidney disease must rely more on self-monitoring of blood glucose with usual glucose meters. Patients with diabetes and CKD have usually already established CVD. These patients are also in greater risk of hypoglycaemia. We know from physiology that normal renal function conveys a 30% of neoglycogenesis, which is necessary to avoid hypoglycaemia especially in prolonged fasting periods[6].

Many diabetics with uraemia have also nutritional problems and some times cachexia. The use of insulin as well as of sulfonylureas or glinides (short acting secretagogues) leads to increased rate of hypoglycaemia in this group of patients[7,8].

On the other hand, many drugs have renal metabolism and their metabolites are usually active prolonging their time of action. The use of antidiabetic drugs, especially the new classes, is conflicted. The major problem is that in many efficacy studies patients with CKD are excluded so data of safety and efficacy for these patients are missing. This results in fear of use by lack of evidence[9].

Nevertheless, pharmacokinetics and pharmacodynamics data for many new drugs help us to understand the potential risks and benefits for these subjects. Even if these basic data are reassuring the clinical point remains critical: We cannot use new drugs based only on these evidence! We need results form efficacy studies and then approval from FDA and EMEA[10].

Finally, the use of antidiabetic drugs is more complicated in these patients because many people with kidney disease are often elderly, and have long lasting disease and significant co-morbidities. These people take many drugs and they have high risk of drug interactions.

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