Can sulphonylurea addition to lifestyle changes help to delay diabetes development in subjects with impaired fasting glucose? The Nepi ANtidiabetes StudY (NANSY).

The Nepi ANtidiabetes StudY (NANSY) is a 5-year randomized, double-blind, placebo-controlled trial in Swedish primary care, examining whether the development of type 2 diabetes (T2D) and retinopathy (separately reported) would be delayed in 40- to 70-year-old subjects with impaired fasting glucose (IFG) who, in addition to lifestyle changes, were treated with either placebo or low-dosage sulphonylurea (SU) (1-mg glimepiride; Amaryl). Of 274 subjects (163 men, 111 women), 138 were allocated to placebo (46.0% men, 56.8% women) and 136 to glimepiride (54.0% men, 43.2% women). The primary endpoint was conversion to diabetes. Average follow-up time was 3.71 years; 96 subjects converted to diabetes, 55 allocated to placebo and 41 to glimepiride (absolute difference 9.8%; p = 0.072). In conclusion, the study failed to support the notion that low-dose SU added to lifestyle changes in IFG subjects would help to delay the conversion to diabetes.

Differences in pharmacotherapy and in glucose control of type 2 diabetes patients in two neighbouring towns: a longitudinal population-based study.

AIM: To compare prescribing, dosage and blood glucose levels in patients with type 2 diabetes in two communities with differences in anti-hyperglycaemic drug utilization. METHODS: A retrospective longitudinal (1984-1994) population-based study in two neighbour towns in southern Sweden. The mean prescribed daily dose was expressed as a fraction of the Defined Daily Dose (DDD) for each drug. RESULTS: In town A, prescribing of oral agents and insulin was predominantly made by one specialized diabetes clinician, while in town B it was spread among several different general practitioners and one specialist. Altogether 44 636 medical visits by 2348 patients were identified. In each town, about 40% of the patients were treated without anti-hyperglycaemic drugs, about 40% with oral agents and about 20% with insulin. However, there were pronounced between-town differences in dosage and glucose control. The mean prescribed daily dose of sulphonylurea monotherapy decreased gradually from approximately 0.7 to approximately 0.5 DDD in town B but remained approximately 0.8 DDD in town A. The proportion of patients on both sulphonylurea and metformin increased substantially in town A but not in town B. In these patients, the mean prescribed daily dose of sulphonylurea exceeded 1.0 DDD in both towns, although it decreased with time in town B. The mean prescribed daily dose of insulin increased from 1.05 to 1.2 DDD in town A but remained virtually unchanged at 0.95 DDD in town B. The mean fasting blood glucose was lower in town A than in town B both overall (7.7 vs. 8.8 mmol/l), in those treated without any anti-hyperglycaemic drugs (7.2 vs. 8.1 mmol/l), in those on sulphonylurea monotherapy (8.3 vs. 9.7 mmol/l) and in those treated with insulin (8.1 vs. 10.2 mmol/l). CONCLUSIONS: Glucose control in routine care was better when most patients were treated by a diabetes specialist and were exposed to more intense pharmacotherapy.

The NEPI antidiabetes study (NANSY). 1: short-term dose-effect relations of glimepiride in subjects with impaired fasting glucose.

AIM: NANSY is a randomised, placebo-controlled Swedish-Norwegian study which aims to include 2 x 1112 male and female subjects with impaired fasting glucose (IFG), to assess whether conversion to type 2 diabetes can be delayed by addition of sulphonylurea to dietary regulation and increased exercise. This pilot study was conducted to find the optimum dose of glimepiride in NANSY. METHODS: In a double blind trial in primary care 25 IFG subjects were in random order exposed to single doses and one-week treatments with 0 (placebo), 0.5, 1.0 and 2.0 mg glimepiride once daily. The optimum dose was assessed by measuring blood glucose during oral 75 g glucose tolerance test (OGTT), comparing fasting blood glucose, and the area under the blood glucose curve (AUC), and by monitoring hypoglycaemic events. RESULTS: With single doses, there was a clear dose-response relationship for the reduction in AUC, with a statistically significant difference only between placebo (mean 1981, 95% confidence intervals (CI) 1883-2078) and 2 mg glimepiride (mean 1763, 95% CI 1665-1861). However, following 1-week treatments, the only significant difference was between placebo (mean 1934, 95% CI 1856-2012) and 1 mg glimepiride (mean 1714, 95% CI 1637-1792). Correspondingly, the only statistically significant difference in fasting blood glucose day 7 was between placebo (5.87 mmol/l, 95% CI 5.68-6.05 mmol/l) and 1 mg glimepiride (5.42 mmol/l, 95% CI 5.21-5.62 mmol/l). Chemical hypoglycaemia was common but hypoglycaemic symptoms were rare and similar between the active doses, and easily countered by the subjects. CONCLUSIONS: The sulphonylurea dose-effect curve may be bell-shaped, perhaps due to down regulation of sulphonylurea receptors during chronic exposure. Alternatively, the finding could be a rebound phenomenon, secondary to preceding hypoglycaemia. The optimum dose for NANSY was found to be 1 mg glimepiride.

Increased mortality in Type II diabetic patients using sulphonylurea and metformin in combination: a population-based observational study.

AIMS/HYPOTHESIS: This study analysed cause-specific mortality in Type II (non-insulin-dependent) diabetic patients using either sulphonylurea alone or in combination with metformin. METHODS: Patients were followed from the first day they were taking either the combination or sulphonylurea alone. Odds ratios by Cox regression analyses were adjusted for age, sex, duration of diabetes, study area, year of inclusion and fasting blood glucose at inclusion. RESULTS: We included 169 patients taking sulphonylurea and metformin in combination and 741 patients taking only sulphonylurea. Mean (range) follow-up time was 6.1 (0.1-13.0) years. The adjusted odds ratio for overall mortality was 1.63 (95% confidence interval 1.27-2.09) in patients taking sulphonylurea and metformin combination vs those using sulphonylurea alone. For mortality from ischaemic heart disease and stroke the adjusted odds ratios were 1.73 (95% confidence interval 1.17-2.55) and 2.33 (95% confidence interval 1.17-4.63), respectively. CONCLUSION/INTERPRETATION: There was a higher cardiovascular mortality in Type II diabetic patients taking sulphonylurea and metformin in combination than in those taking only sulphonylurea. Hence, it cannot be excluded that this kind of combination therapy possibly increases cardiovascular mortality. It is feasible that the increased mortality was secondary to a more aggressive type of diabetes in the patients using sulphonylurea and metformin in combination. Combination therapy is known to promote additional blood glucose reduction but there is as yet no evidence that a sulphonylurea and metformin combination is more beneficial on micro- or macrovascular disease than sulphonylurea or metformin alone.