Problems and Pitfalls of Sulphonylurea Therapy in Older Patients

Abstract

The prevalence of non-insulin-dependent diabetes mellitus (type II) increases with age, so that approximately half of all known patients in English-speaking countries are over 65 years of age. There is no reason to believe that the criteria for blood glucose control should be any less stringent for elderly patients unless they have a limited life expectancy. Sulphonylurea drugs remain an effective means of achieving blood glucose control after failure of dietary therapy alone in older patients. However, changes in normal metabolism of drugs with age and the development of other pathologies in elderly patients make it important that these drugs are prescribed with care. Severe symptomatic hypoglycaemia is the most serious adverse effect of sulphonylurea drugs and this becomes progressively more likely with increasing age, depending primarily on the substantial reduction of renal function with normal aging. Other adverse effects are much less commonly of clinical importance. To minimise the risk of hypoglycaemia, it is important that patients receive closely supervised dietary management with education about their disease for at least 3 months before sulphonylurea drugs are prescribed. In elderly patients a short-acting agent with no active metabolites should be used. As patients become older, those receiving long-acting agents can be changed to short-acting agents before problems arise. If blood glucose control appears satisfactory on treatment, then symptoms of hypoglycaemia should be sought. If control is poor, then the criteria for introduction of insulin, with appropriate education, do not differ from those in younger patients.

Diabetes mellitus – an overview

“…They are most likely to be effective in patients whose weight is in the normal range [80]. Hypoglycaemia is the most troublesome effect and is more common with second-generation SUs, which have longer half-lives [87]. SU drugs such as tolazamide, acetohexamide, chlorpropamide and glibenclamide (glyburide) are more likely to cause signifi cant hypoglycaemia, as the metabolism of these drugs, compared with other commonly prescribed SUs, can lead to the accumulation of either the parent drug or the active metabolite in the presence of renal insuffi ciency.…”

Review of prandial glucose regulation with repaglinide: a solution to the problem of hypoglycaemia in the treatment of Type 2 diabetes?

“…This risk will also be compounded when sulphonylureas that are renally excreted (or that have renally-excreted active metabolites) are used in patients with compromised renal function. 45 Food intake may also adversely affect the temporal pro®le of stimulated insulin secretion during sulphonylurea therapy. Single dose studies have shown 2.5 mg of glibenclamide taken 30 min before breakfast to be more effective than 7.5 mg taken with breakfast, 46 while concomitant food intake has been shown to delay the absorption of glipizide.…”

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“…The prolonged action of these drugs means that stimulation of insulin release extends well beyond mealtimes, and may therefore be inappropriately high when glucose levels are not elevated. Under these circumstances, hypoglycemia is an ever-present risk, and the patient treated with a SU must ensure an adequate carbohydrate intake throughout the day to counter this threat; a missed meal is particularly likely to result in a hypoglycemic episode (35,36). Indeed, symptomatic hypoglycemia is the most common side effect associated with SU therapy, particularly in elderly patients, and irregular meals have been identified as a contributing factor in this high incidence (35).…”

“…Under these circumstances, hypoglycemia is an ever-present risk, and the patient treated with a SU must ensure an adequate carbohydrate intake throughout the day to counter this threat; a missed meal is particularly likely to result in a hypoglycemic episode (35,36). Indeed, symptomatic hypoglycemia is the most common side effect associated with SU therapy, particularly in elderly patients, and irregular meals have been identified as a contributing factor in this high incidence (35). Accumulation of SUs that are partially excreted by the renal route may be another reason for an increased risk of hypoglycemia in elderly patients (35).…”

“…Indeed, symptomatic hypoglycemia is the most common side effect associated with SU therapy, particularly in elderly patients, and irregular meals have been identified as a contributing factor in this high incidence (35). Accumulation of SUs that are partially excreted by the renal route may be another reason for an increased risk of hypoglycemia in elderly patients (35). The American Diabetes Association and European NIDDM Policy Group have recommended short-acting insulin secretagogues to reduce this risk (37,38).…”