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Aim: The objective of this review was to assess the published evidence for an association between glycaemic variability and the development of chronic micro- and macrovascular complications in patients with diabetes mellitus (DM). Methods: A systematic review of English-language literature published from January 1990 through November 2008 was performed. Interventional and observational studies in patients with type 1 or type 2 DM reporting a measure of glycaemic variability and its impact on the development or progression of micro- and macrovascular diabetic complications were assessed. Results: A total of 18 studies −8 on type 1 DM and 10 on type 2 DM patients–meeting the inclusion criteria were identified. Studies in patients with type 1 DM revealed that glucose variability has little impact on the development of diabetic complications. Only in two of the eight type 1 DM studies did glucose variability have a significant association with microvascular complications, but not with macrovascular complications. Among type 2 DM studies, a significant positive association between glucose variability and the development or progression of diabetic retinopathy, cardiovascular events and mortality was reported in 9 of 10 studies. Only one type 2 DM study reported no association between glucose variability and progression of retinopathy. Conclusions: Based on this overview of the available evidence, there appears to be a signal suggesting that glucose variability, characterized by extreme glucose excursions, could be a predictor of diabetic complications, independent of HbA1c levels, in patients with type 2 DM. Better daily control of blood glucose excursions, especially in the postprandial period, may reduce the risk of these complications. Future prospective trials evaluating and comparing the effect of the control of glycaemic variability on the development of diabetic micro- and macrovascular complications are needed to further strengthen the evidence base. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to quantify the effect of a sulphonylurea on glycaemic control and the risk adverse events when incorporated into the treatment regimen of patients with type 2 diabetes inadequately controlled on metformin. Methods: A systematic review was carried out to identify randomized controlled trials of sulphonylurea therapy in patients with type 2 diabetes whose glycaemic control was inadequate after maximal treatment with metformin. Data on reductions in haemoglobin A1C (HbA1C), fasting plasma glucose (FPG) and risk of hypoglycaemic events were extracted from each study and pooled in meta-analyses. Data on weight change were also extracted and tabulated. Results: Six studies including 1364 patients were identified. Based on random effects meta-analysis, the pooled estimate of change in HbA1C from baseline was 0.9% (95% CI 0.7–1.1, p = 0.00011 vs. baseline) and for change in FPG from baseline was 1.8 mmol/l (95% CI 1.1–2.5, p = 0.0026 vs. baseline). The odds of experiencing a hypoglycaemic event was significantly higher in sulphonylurea-treated patients than in those on comparator treatments (OR = 5.3, 95% CI 1.7–16.3, p = 0.03). Mean weight change ranged from +2.5 to −0.1 kg, depending on the comparator treatment. Conclusions: This analysis has demonstrated that, in patients with type 2 diabetes whose control is inadequate on metformin monotherapy, the magnitude of incremental HbA1C reduction achieved by the addition of a sulphonylurea is unlikely to exceed 1%, even after titration to maximum tolerated doses. Additionally, clinically relevant side-effects such as symptomatic hypoglycaemia and weight gain may be experienced. [ABSTRACT FROM AUTHOR]

Context: Hypoglycaemia from antihyperglycaemic drugs may have a significant impact on patients’ health-related quality of life. Combination use of metformin and a sulphonylurea has become increasingly common; yet, the impact of hypoglycaemia on quality of life in these patients is not well documented. Objective: To examine patient-reported experience of hypoglycaemia, worry about hypoglycaemic symptoms and the impact of hypoglycaemia on patients’ quality of life associated with use of sulphonylurea co-administered with metformin. Design: This was an observational, cross-sectional, multi-centre study. Setting: A total of 98 primary care centres in France during October to December 2005. Patients: A total of 400 patients with type 2 diabetes, who were ≥35 years old and who had been treated with metformin and a sulphonylurea for at least 6 months, completed questionnaires during their usual primary care office visit. Main Outcome Measures: Frequency and severity of hypoglycaemic symptoms in the past 6 months, the Worry subscale of the Hypoglycaemic Fear Survey-II (HFS-II) and the EuroQol-5 Dimensions (EQ-5D) questionnaire. Results: A total of 136 (34%) patients reported experiencing hypoglycaemia, of whom 78 (58%) experienced mild, 40 (30%) experienced moderate and 16 (12%) experienced severe or very severe symptoms. Mean score on the HFS-II Worry scale was higher for patients who reported having hypoglycaemia than for those who did not (19.0 vs. 10.2; p < 0.0001) and increased with severity of hypoglycaemic symptoms. In linear regression analyses, more severe symptoms of hypoglycaemia were significantly associated with higher scores on the HFS-II Worry scale (p = 0.0162) among patients with hypoglycaemic symptoms. Summary scores on the EQ-5D were lower for patients who reported hypoglycaemia than for those who did not (p = 0.0001) and, in multivariate analysis, the experience of hypoglycaemia was negatively associated with the EQ-5D summary score (p < 0.0001). Conclusion: The occurrence and severity of hypoglycaemic symptoms were associated with increased patient worry about hypoglycaemia and lower health-related quality of life among type 2 diabetic patients being treated with both metformin and a sulphonylurea. [ABSTRACT FROM AUTHOR]

Aims: This study was undertaken to evaluate (i) factors associated with patient-reported hypoglycaemia; (ii) association of patient-reported hypoglycaemic symptoms with treatment satisfaction and barriers to adherence and (iii) association between treatment satisfaction, adherence and glycaemic control among patients with type 2 diabetes who added a sulphonylurea or a thiazolidinedione to ongoing metformin. Methods: This observational, cross-sectional, multicentre study was conducted in seven countries (Finland, France, Germany, Norway, Poland, Spain and UK) from June 2006 to February 2007. Patients with type 2 diabetes who added a sulphonylurea or a thiazolidinedione to ongoing metformin therapy on a date (index date) from January 2001 through January 2006 and who had at least one haemoglobin A1C (HbA1C) measurement in the 12-month period before the visit date were eligible. Questionnaires were used to ascertain patients’ reports of hypoglycaemic symptoms, treatment satisfaction, and treatment adherence. The Treatment Satisfaction Questionnaire for Medication was used to measure patients’ treatment satisfaction. An adherence and barriers questionnaire was used to measure patients’ adherence to treatment. Glycaemic control was based on documented HbA1C measurements within the prior 12 months. Results: The mean ± s.d. age was 62.9 ± 10.6 years, and the mean ± s.d. duration of diabetes was 7.8 ± 5.1 years. HbA1C in this population of patients who had failed metformin monotherapy and were treated with oral antihyperglycaemic agents was below the International Diabetes Federation goal of 6.5% in only 477 (27.9%) patients. Approximately 38% of patients reported hypoglycaemic symptoms during the past year. Hypoglycaemia was significantly more likely in patients with a history of macrovascular complications of diabetes (OR = 1.346; 95% CI = 1.050–1.725) and with no regular physical activity (OR = 1.295; 95% CI = 1.037–1.618). Patients reporting hypoglycaemia had significantly lower treatment satisfaction scores (71.6 ± 17.6 vs. 76.3 ± 16.8; p < 0.0001 for global satisfaction). Compared with their counterparts reporting no hypoglycaemic symptoms, patients with such symptoms were also significantly more likely to report barriers to adherence, including being unsure about instructions (37.0 vs. 30.5%; p = 0.0057). Patients at HbA1C goal had significantly higher treatment satisfaction and adherence compared with those who were not. Conclusions: Patients’ reports of hypoglycaemic symptoms are common in European outpatients with type 2 diabetes and are associated with significantly lower treatment satisfaction and with barriers to adherence. In addition, being at HbA1C goal is associated with treatment satisfaction and adherence. [ABSTRACT FROM AUTHOR]

Objective: Sitagliptin is a novel oral incretin enhancer that acts by inhibiting the dipeptidyl peptidase 4 enzyme and is indicated in Europe as a treatment adjunct to metformin (MF), sulphonylurea (SU), MF plus SU and diet and exercise, in the management of type 2 diabetes mellitus. The objective of the current analysis was to evaluate the cost-effectiveness of adding sitagliptin to the regimens of patients with haemoglobin A1c (HbA1C) above the International Diabetes Federation goal (6.5%) while on MF in six European countries: Austria, Finland, Portugal, Scotland (United Kingdom), Spain and Sweden. Methods: A discrete event simulation model, which employed the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model risk equations for predicting risks of diabetes-related complication, was used. Lifetime costs and benefits were projected for alternative treatment strategies of adding sitagliptin, compared with adding rosiglitazone or a SU to MF in patients not at HbA1C goal on MF monotherapy. Changes in HbA1C as well as side effects associated with these different treatment strategies were based on clinical trial data. Mean baseline values from local epidemiologic studies involving patients with type 2 diabetes not at HbA1C goal on MF monotherapy were included in the current analysis. Costs of medications, side effects and direct costs of diabetes-related complications were based on country-specific data. UKPDS-based disutility weights associated with diabetes complications were incorporated. Disutilities associated with medication side effects were based on published data. All future costs and benefits were discounted according to local guidelines on cost-effectiveness analysis. One-way sensitivity analyses were conducted by varying key input parameters. Findings: The discounted incremental cost-effectiveness ratios (ICER) associated with the addition of sitagliptin to MF, compared with adding rosiglitazone, in the different countries analysed ranged from treatment with sitagliptin being dominant (cost saving with improved health outcome) to its being cost-effective [€4,766 per quality-adjusted life year (QALY)]. Treatment with sitagliptin added to MF was cost-effective compared with adding a SU, with discounted ICER values ranging from €5949/QALY to €20 350/QALY across countries. Sensitivity analyses showed that these results were robust to changes in input parameters, including clinical efficacy, costs and utility weights for both diabetes-related complications and hypoglycaemia. Conclusions: Compared with adding rosiglitazone or a SU to MF, adding sitagliptin to MF is projected to be either cost saving or cost-effective for patients with type 2 diabetes who are not at HbA1C goal on MF. [ABSTRACT FROM AUTHOR]