Fifty-two-week efficacy and safety of vildagliptin vs. glimepiride in patients with type 2 diabetes mellitus inadequately controlled on metformin monotherapy

To examine the efficacy and safety of vildagliptin vs. glimepiride as add-on therapy to metformin in patients with type 2 diabetes mellitus in a 52-week interim analysis of a large, randomized, double-blind, multicentre study. The primary objective was to demonstrate non-inferiority of vildagliptin vs. glimepiride in glycosylated haemoglobin (HbA(1c)) reduction at week 52. Patients inadequately controlled on metformin monotherapy (HbA(1c) 6.5-8.5%) and receiving a stable dose of metformin (mean dose 1898 mg/day; mean duration of use 36 months) were randomized 1:1 to receive vildagliptin (50 mg twice daily, n = 1396) or glimepiride (titrated up to 6 mg/day; mean dose 4.5 mg/day, n = 1393). Non-inferiority of vildagliptin was demonstrated (97.5% confidence interval 0.02%, 0.16%) with a mean (SE) change from baseline HbA(1c) (7.3% in both groups) to week 52 endpoint of -0.44% (0.02%) with vildagliptin and -0.53% (0.02%) with glimepiride. Although a similar proportion of patients reached a target HbA(1c) level of < 7% with vildagliptin and glimepiride (54.1 and 55.5%, respectively), a greater proportion of patients reached this target without hypoglycaemia in the vildagliptin group (50.9 vs. 44.3%; p < 0.01). Fasting plasma glucose (FPG) reductions were comparable between groups (mean [SE] -1.01 [0.06] mmol/l and -1.14 [0.06] mmol/l respectively). Vildagliptin significantly reduced body weight relative to glimepiride (mean [SE] change from baseline -0.23 [0.11] kg; between-group difference -1.79 kg; p < 0.001) and resulted in a 10-fold lower incidence of hypoglycaemia than glimepiride (1.7 vs. 16.2% of patients presenting at least one hypoglycaemic event; 39 vs. 554 hypoglycaemic events, p < 0.01). No severe hypoglycaemia occurred with vildagliptin compared with 10 episodes with glimepiride (p < 0.01), and no patient in the vildagliptin group discontinued because of hypoglycaemia compared with 11 patients in the glimepiride group. The incidence of adverse events (AEs), serious AEs and adjudicated cardiovascular events was 74.5, 7.1 and 0.9%, respectively, in patients receiving vildagliptin, and 81.1, 9.5 and 1.6%, respectively, in patients receiving glimepiride. When metformin alone fails to maintain sufficient glycaemic control, the addition of vildagliptin provides comparable efficacy to that of glimepiride after 52 weeks and displays a favourable AE profile, with no weight gain and a significant reduction in hypoglycaemia compared with glimepiride

Caregiver perspectives on pain sensitivity and pain experience in Rett syndrome

ABSTRACTBackground: Although delayed or decreased responses to pain are commonly reported among caregivers of individuals with Rett syndrome (RTT), previous studies in relatively small samples have documented that caregivers are concerned about pain, particularly due to gastrointestinal and musculoskeletal conditions.Aims: The purpose of the current study was to investigate detail caregivers’ perception of pain sensitivity, as well as the types, severity, and impact of pain experienced by individuals with RTT in a larger sample than previous studies.Methods: A total of 51 caregivers (mostly mothers) participated in the study, which involved standardized questionnaires and interviews. The individuals with RTT ranged in age from 2 to 52 years of age, and most (n = 46; 90%) met criteria for classic RTT.Results: Across the sample, 84% of caregivers reported that they believed that their child was less sensitive to pain compared to her typically developing peers. Despite this perception, 63% of caregivers reported that their child had experienced at least one form of pain in the previous 7 days, and 57% reported their child experienced at least one form of chronic pain. On average, caregivers reported that their child’s pain was of moderate severity and interfered with at least one activity of daily living.Conclusions: The results suggest that pain is a substantial concern among caregivers of individuals with RTT and indicate that additional research is needed to understand the apparent paradox of frequently reported pain experiences despite widespread perceptions of decreased pain sensitivity

Fifty-two-week efficacy and safety of vildagliptin vs. glimepiride in patients with type 2 diabetes mellitus inadequately controlled on metformin monotherapy.

AIM: To examine the efficacy and safety of vildagliptin vs. glimepiride as add-on therapy to metformin in patients with type 2 diabetes mellitus in a 52-week interim analysis of a large, randomized, double-blind, multicentre study. The primary objective was to demonstrate non-inferiority of vildagliptin vs. glimepiride in glycosylated haemoglobin (HbA(1c)) reduction at week 52. METHODS: Patients inadequately controlled on metformin monotherapy (HbA(1c) 6.5-8.5%) and receiving a stable dose of metformin (mean dose 1898 mg/day; mean duration of use 36 months) were randomized 1:1 to receive vildagliptin (50 mg twice daily, n = 1396) or glimepiride (titrated up to 6 mg/day; mean dose 4.5 mg/day, n = 1393). RESULTS: Non-inferiority of vildagliptin was demonstrated (97.5% confidence interval 0.02%, 0.16%) with a mean (SE) change from baseline HbA(1c) (7.3% in both groups) to week 52 endpoint of -0.44% (0.02%) with vildagliptin and -0.53% (0.02%) with glimepiride. Although a similar proportion of patients reached a target HbA(1c) level of &lt;7% with vildagliptin and glimepiride (54.1 and 55.5%, respectively), a greater proportion of patients reached this target without hypoglycaemia in the vildagliptin group (50.9 vs. 44.3%; p &lt; 0.01). Fasting plasma glucose (FPG) reductions were comparable between groups (mean [SE] -1.01 [0.06] mmol/l and -1.14 [0.06] mmol/l respectively). Vildagliptin significantly reduced body weight relative to glimepiride (mean [SE] change from baseline -0.23 [0.11] kg; between-group difference -1.79 kg; p &lt; 0.001) and resulted in a 10-fold lower incidence of hypoglycaemia than glimepiride (1.7 vs. 16.2% of patients presenting at least one hypoglycaemic event; 39 vs. 554 hypoglycaemic events, p &lt; 0.01). No severe hypoglycaemia occurred with vildagliptin compared with 10 episodes with glimepiride (p &lt; 0.01), and no patient in the vildagliptin group discontinued because of hypoglycaemia compared with 11 patients in the glimepiride group. The incidence of adverse events (AEs), serious AEs and adjudicated cardiovascular events was 74.5, 7.1 and 0.9%, respectively, in patients receiving vildagliptin, and 81.1, 9.5 and 1.6%, respectively, in patients receiving glimepiride. CONCLUSIONS: When metformin alone fails to maintain sufficient glycaemic control, the addition of vildagliptin provides comparable efficacy to that of glimepiride after 52 weeks and displays a favourable AE profile, with no weight gain and a significant reduction in hypoglycaemia compared with glimepiride