Efficacy and safety of Subetta add-on therapy in type 1 diabetes mellitus: The results of a multicenter, double-blind, placebo-controlled, randomized clinical trial.

BACKGROUND: To examine efficacy of Subetta as an add-on to insulin therapy in patients with type 1 diabetes mellitus (T1DM) a multicenter, double-blind, placebo-controlled, randomized clinical trial was performed. Derived by technological treatment of antibodies to insulin receptor ß-subunit and endothelial NO synthase Subetta was previously proved to activate insulin signaling pathway. METHODS: A total of 144 randomized patients with poor glycemic control in basal-bolus insulin regime were included in intention-to-treat analysis in Subetta add-on therapy or placebo (n = 72 in both groups). Hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), basal and prandial insulin doses, number of hypoglycemia episodes confirmed by self-monitoring of blood glucose were recorded for 36 weeks. RESULTS: The baseline characteristics of subjects did not differ between the two groups. HbA1c mean (±standard deviation) change was -0.59 ±â€¯0.99% (95% CI -0.84 to -0.37) after 36 weeks in Subetta (vs. -0.20 ±â€¯1.14%; 95% CI -0.44 to 0.11 in placebo; p = 0.028). The rate of overall hypoglycemia events was 7.9 per patient year (95% CI 7.1-8.6) in Subetta group and 7.6 (95% CI 6.9-8.4) in Placebo group (p = 0.63). The basal and total insulin doses did not change at the end of 36 weeks in both groups. CONCLUSIONS: Subetta add-on therapy boosting insulin activity and improving glycemic control in patients with T1DM is proved to be beneficial. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01868594.

Equal improvement in glycaemia with lixisenatide given before breakfast or the main meal of the day.

AIMS: The aim of this study is to explore whether administration timing affects glycaemic control by lixisenatide once-daily in type 2 diabetes mellitus (T2DM). METHODS: A phase IIIb, open-label, 1:1 randomized, active-controlled, 24-week multicentre study of T2DM patients inadequately controlled on metformin was conducted. Patients were administered lixisenatide before breakfast or the main meal. The primary endpoint was change from baseline at week 24 in glycated haemoglobin (HbA1c). Other endpoints: changes in body weight, fasting plasma glucose (FPG), 7-point self-monitored plasma glucose (SMPG) and Diabetes Treatment Satisfaction Questionnaire status (DTSQs) score. Adverse events (AEs) were monitored. RESULTS: Mean change in HbA1c from baseline at week 24 was -0.65% (-7.1mmol/mol; main meal) and -0.74% (-8.1mmol/mol; breakfast). Mean changes in FPG, body weight and DTSQs score were comparable between groups. The mean change in body weight (kg) was -2.60 (main meal) and -2.80 (breakfast group). The 7-point SMPG profiles showed greatest reductions in postprandial glucose after the meal at which lixisenatide was administered, with a residual effect seen on the subsequent meal. AE rates were similar between groups, including gastrointestinal AEs. CONCLUSIONS: Lixisenatide before the main meal was noninferior to lixisenatide before breakfast in patients insufficiently controlled on metformin. Lixisenatide treatment allows flexibility in administration timing.

Macrophage stimulating agent soluble yeast ß-1,3/1,6-glucan as a topical treatment of diabetic foot and leg ulcers: A randomized, double blind, placebo-controlled phase II study.

AIMS/INTRODUCTION: Dysregulated inflammatory response is believed to be an important factor in the pathogenesis of several late complications of diabetes mellitus. ß-Glucans are potent inducers of immune function. The present randomized, double blind, two-center, placebo-controlled study was undertaken to explore safety, tolerability and efficacy of soluble ß-1,3/1,6-glucan (SBG) as a local treatment of diabetic foot ulcers. MATERIALS AND METHODS: A total of 60 patients with type 1 or 2 diabetes and lower extremity ulcers (Wagner grade 1-2, Ankle/Brachial Index ≥0.7) received SBG or a comparator product (methylcellulose) locally three times weekly up to 12 weeks in addition to conventional management scheme. A total of 54 patients completed the study. RESULTS: A tendency for shorter median time to complete healing in the SBG group was observed (36 vs 63 days, P = 0.130). Weekly percentage reduction in ulcer size was significantly higher in the SBG group than in the methylcellulose group between weeks 1-2, 3-4 and 5-6 (P < 0.05). The proportion of ulcers healed by week 12 was also in favor of SBG (59% vs 37%, P = 0.09), with a significantly higher healing incidence in the SBG group at week 8 (44% vs 17%, P = 0.03). SBG was safe and well tolerated. There was a clinically significant difference regarding the incidence of serious adverse events in favor of the SBG treatment. CONCLUSIONS: Local treatment of diabetic lower extremity ulcers with ß-1,3/1,6-polyglucose shows good safety results. This ß-glucan preparation shows promising potential as a treatment accelerating cutaneous healing. Further studies are required to confirm this effect. This trial was registered with ClinicalTrials.gov (no. NCT00288392).