A New Approach to Overcome Insulin Resistance in Patients with Impaired Glucose Tolerance: The Results of a Multicenter, Double-Blind, Placebo-Controlled, Randomized Clinical Trial of Efficacy and Safety of Subetta.

Impaired glucose tolerance (IGT) is a common carbohydrate metabolism disorder world-wide. To evaluate the efficacy and safety of 12-week Subetta therapy in correcting 2-h plasma glucose in patients with IGT, 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 increases the sensitivity of insulin receptors by activating the insulin signaling pathway. Oral glucose tolerance test (OGTT), fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c) were examined at screening, after 4 and 12 weeks. In Per Protocol population, 2-h plasma glucose in the Subetta group decreased by 2.05 ± 2.11 mmol/L (versus 0.56 ± 2.55 mmol/L in the Placebo group) after 12 weeks. The difference between the two groups was 1.49 ± 2.33 mmol/L (p < 0.0001). After 12 weeks, 65.2% of patients had 2-h plasma glucose <7.8 mmol/L. FPG remained almost unchanged. HbA1c tended to decrease. The number of adverse events did not differ in both groups. Subetta treatment is beneficial for patients with IGT; it also prevents progression of carbohydrate metabolism disorders.

Drift of the Subgingival Periodontal Microbiome during Chronic Periodontitis in Type 2 Diabetes Mellitus Patients.

Since periodontitis and type 2 diabetes mellitus are complex diseases, a thorough understanding of their pathogenesis requires knowing the relationship of these pathologies with other disorders and environmental factors. In this study, the representability of the subgingival periodontal microbiome of 46 subjects was studied by 16S rRNA gene sequencing and shotgun sequencing of pooled samples. We examined 15 patients with chronic periodontitis (CP), 15 patients with chronic periodontitis associated with type 2 diabetes mellitus (CPT2DM), and 16 healthy subjects (Control). The severity of generalized chronic periodontitis in both periodontitis groups of patients (CP and CPT2DM) was moderate (stage II). The male to female ratios were approximately equal in each group (22 males and 24 females); the average age of the subjects was 53.9 ± 7.3 and 54.3 ± 7.2 years, respectively. The presence of overweight patients (Body Mass Index (BMI) 30-34.9 kg/m2) and patients with class 1-2 obesity (BMI 35-45.9 kg/m2) was significantly higher in the CPT2DM group than in patients having only chronic periodontitis or in the Control group. However, there was no statistically significant difference in all clinical indices between the CP and CPT2DM groups. An analysis of the metagenomic data revealed that the alpha diversity in the CPT2DM group was increased compared to that in the CP and Control groups. The microbiome biomarkers associated with experimental groups were evaluated. In both groups of patients with periodontitis, the relative abundance of Porphyromonadaceae was increased compared to that in the Control group. The CPT2DM group was characterized by a lower relative abundance of Streptococcaceae/Pasteurellaceae and a higher abundance of Leptotrichiaceae compared to those in the CP and Control groups. Furthermore, the CP and CPT2DM groups differed in terms of the relative abundance of Veillonellaceae (which was decreased in the CPT2DM group compared to CP) and Neisseriaceae (which was increased in the CPT2DM group compared to CP). In addition, differences in bacterial content were identified by a combination of shotgun sequencing of pooled samples and genome-resolved metagenomics. The results indicate that there are subgingival microbiome-specific features in patients with chronic periodontitis associated with type 2 diabetes mellitus.

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.

A global study of the unmet need for glycemic control and predictor factors among patients with type 2 diabetes mellitus who have achieved optimal fasting plasma glucose control on basal insulin.

BACKGROUND: This study used data from different sources to identify the extent of the unmet need for postprandial glycemic control in patients with type 2 diabetes mellitus (T2DM) after the initiation of basal insulin therapy in Europe, Asia Pacific, the United States, and Latin America. METHODS: Different levels of evidence were used as available for each country/region, with data extracted from seven randomized controlled trials (RCTs), three clinical trial registries (CTRs), and three electronic medical record (EMR) databases. Glycemic status was categorized as "well controlled" (glycated hemoglobin [HbA1c ] at target [<7%]), "residual hyperglycemia" (fasting plasma glucose [FPG] but not HbA1c at target [FPG <7.2/7.8 mmol/L, <130/140 mg/dL, depending on country-specific recommendations]), or "uncontrolled" (both FPG and HbA1c above target). Predictor factors were identified from the RCT data set using logistic regression analysis. RESULTS: RCT data showed that 16.9% to 28.0%, 42.7% to 54.4%, and 16.9% to 38.1% of patients with T2DM had well-controlled glycemia, residual hyperglycemia, and uncontrolled hyperglycemia, respectively. In CTRs, respective ranges were 21.8% to 33.6%, 31.5% to 35.6%, and 30.7% to 46.8%, and in EMR databases were 4.4% to 21.0%, 23.9% to 31.8%, and 53.6% to 63.8%. Significant predictor factors of residual hyperglycemia identified from RCT data included high baseline HbA1c (all countries/regions except Brazil), high baseline FPG (United Kingdom/Japan), longer duration of diabetes (Brazil), and female sex (Europe/Latin America). CONCLUSIONS: Irrespective of intrinsic differences between data sources, 24% to 54% of patients with T2DM globally had residual hyperglycemia with HbA1c not at target, despite achieving FPG control, indicating a significant unmet need for postprandial glycemic control.