In people with type 2 diabetes, glimepiride was associated with fewer episodes of severe hypoglycaemia than glibenclamide in routine clinical use. However, severe hypoglycaemia did occur with glimepiride and may be minimised if treatment targets are determined on an individual basis.

In patients with Type 2 diabetes, the appropriate intensity of glucose control is determined by age, life expectancy, and the presence of concomitant disease. Geriatric patients are especially susceptible to hypoglycaemia and therefore particular care should be taken in this group characterized by polypharmacy, renal or hepatic dysfunction, cardiovascular multimorbidity and malnutrition. As hypoglycaemia is a significant cause of morbidity and mortality, treatment regimens for diabetes should minimize the occurrence of hypoglycaemic episodes and be tailored to the patient's individual needs. The pharmacological options for treating Type 2 diabetes have increased considerably and the risk of hypoglycaemia of the currently available drugs varies considerably. Metformin, thiazolidinediones, and acarbose, oral antidiabetic drugs that decrease insulin resistance or postprandial glucose absorption, are associated with a low risk of hypoglycaemia. These drugs can also be used effectively in various combination regimens; however, by improving insulin sensitivity, combinations of metformin and thiolidinediones with sulphonylureas or meglitinides may considerably increase the risk of hypoglycaemia. On account of its complex pharmacoprofile glibenclamide is a problematic substance carrying a high risk of hypoglycaemia. There are limited preliminary data indicating that, under routine conditions, glimepiride may be associated with a lower risk of hypoglycaemia than glibenclamide and is no more likely to cause hypoglycaemia than other shorter-acting agents such as gliclazide and glipizide. Nateglinide and repaglinide as short-acting insulin secretagogues may be associated with a reduced risk of hypoglycaemia compared with glibenclamide, in particular when dosed flexibly. Repaglinide might be beneficial in individuals with renal impairment.

Despite the considerable risk of lactic acidosis in the majority of patients, no cases were observed.

AimsThe genetically polymorphic cytochrome P450 (CYP) enzyme CYP2C9 metabolizes most sulphonylurea oral hypoglycaemic agents. The aim of this study was to test the hypothesis that individuals with genotypes predicting low CYP2C9 activity may be at a higher risk of severe drug-associated hypoglycaemia. MethodsIn a case-control study, 20 diabetic patients admitted to the emergency department with severe hypoglycaemia during sulphonylurea drug treatment were compared with a control group of 337 patients with type 2 diabetes but without a history of severe hypoglycaemia. A large sample of 1988 healthy Caucasian subjects served as a second control group. ResultsThe CYP2C9 genotypes * 3/ * 3 and *2/*3 that are predictive of low enzyme activity were more common in the hypoglycaemic group than in the comparison groups (10% vs < 2%, respectively: odds ratio 5.2; 95% confidence interval 1.01, 27). Furthermore, the diabetic patient group with severe hypoglycaemia exhibited lower body mass indexes, higher rates of renal failure, were older compared with the diabetic group without severe hypoglycaemia, and were being treated with higher doses of glibenclamide. ConclusionsThese findings suggest that among other factors, individuals with genetically determined low CYP2C9 activity are at an increased risk of sulphonylurea-associated severe hypoglycaemia. Thus, genotyping might be a tool for the better prediction of adverse effects caused by oral hypoglycaemic agents.

In elderly, multimorbid patients approaching the insulin-deficient end of the spectrum of type 2 diabetes the risk of developing SH increases considerably, nearing that in patients with type 1 diabetes. In order to avoid SH in geriatric patients, the treatment targets should be defined critically, taking into account individual quality of life and life expectancy. Hypoglycaemia unawareness is a major risk factor for SH in type 1 diabetes.

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The presence of microalbuminuria is associated with an increased risk for developing nephropathy and cardiovascular diseases in both type 1 and type 2 diabetes (1-3). A proper pharmacological treatment can reduce urinary albumin excretion rate (AER) and prevent clinical nephropathy. Consequently, the screening for microalbuminuria should be an essential tool of the care for diabetic patients.Controversy still exists regarding the type of urine specimen to be used to evaluate microalbuminuria. AER determined in timed urine collections (24 h or overnight) is the most direct measure of urinary albumin excretion (4,5). However, due to the demand of the protocol and frequent imperfect patient adherence, the AER is not practical for epidemiological studies or clinical settings. For these reasons, the measurement of the albumin-tocreatinine ratio (ACR) in a random spot urine has became a widely accepted clinical tool for assessing urinary albumin excretion (6 -8). Recently, several semiquantitative office tests for detecting abnormal albuminuria have been developed (9).The aim of our study was to identify the easiest and most cost-effective screening program for microalbuminuria in an outpatient clinic. We evaluated specificity, sensitivity, and positive (PPV) and negative (NPV) predictive values of measurement of microalbuminuria by using ACR or by an immunological semiquantitative test in a first-morning spot urine sample in comparison with AER measured in three timed overnight urine collections.Urinary albumin concentration was determined by using an immunological semiquantitative test (Micral-test; Roche Diagnostics, Mannheim, Germany) and the ACR by using DCA 2000 Analyzer (Bayer, Mü nchen, Germany) in a firstmorning urine specimen of 1,712 type 2 diabetic patients consecutively admitted to our outpatient clinic. AER was then measured using three timed overnight urine collections that were performed at home a month after the screening evaluation. Albuminuria was detected by immunoturbidimetric method (Image; Beckman). Sensitivity, specificity, PPV, and NPV were calculated to determine the diagnostic properties of Micral and ACR. The AER, calculated as the median of three timed overnight urine collections, was used as the reference indicator. Microalbuminuria was defined as Micral-test Ն20 mg/l or ACR Ͼ2.8 g/mol for women and Ͼ1.9 g/mol for men (10) or AER between 20 and 200 g/min. Patients with urinary tract infections, acetonuria, hematuria, or leucocituria (n ϭ 56) were excluded from the study.In the remaining 1,656 patients eligible for evaluation, the median of AER revealed that 1,273 patients were normoalbuminuric (76.8%), 338 microalbuminuric (20.4%) and 45 macroalbuminuric (2.7%). These figures are similar to those already found in an Italian population (11). Macroalbuminuric patients were excluded from the subsequent analysis.Of the remaining 1,611 patients, 516 patients were classified as microalbuminuric by using Micral-test (194 falsepositive test results and 16 false-negative tests compared with the AE...