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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.

ABSTRACT: 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 β-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.

SUBMITTER: Mkrtumyan A

PROVIDER: S-EPMC8910875 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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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.

Mkrtumyan Ashot A Ametov Alexander A Demidova Tatiana T Volkova Anna A Dudinskaya Ekaterina E Vertkin Arkady A Vorobiev Sergei S

Journal of clinical medicine 20220303 5

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 β-subunit and endothelial NO synthase, Subetta increases the sensitivity of insulin receptors by activating the insulin signaling pat ...[more]

PMID: 35268481

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Project description:BackgroundHigh sugar and refined carbohydrate intake is associated with weight gain, increased incidence of diabetes and is linked with increased cardiovascular mortality. Reducing the health impact of poor quality carbohydrate intake is a public health priority. Reducose, a proprietary mulberry leaf extract (ME), may reduce blood glucose responses following dietary carbohydrate intake by reducing absorption of glucose from the gut.MethodsA double-blind, randomised, repeat measure, phase 2 crossover design was used to study the glycaemic and insulinaemic response to one reference product and three test products at the Functional Food Centre, Oxford Brooks University, UK. Participants; 37 adults aged 19-59 years with a BMI ≥ 20kg/m2 and ≤ 30kg/m2. The objective was to determine the effect of three doses of mulberry-extract (Reducose) versus placebo on blood glucose and insulin responses when co-administered with 50g maltodextrin in normoglycaemic healthy adults. We also report the gastrointestinal tolerability of the mulberry extract.ResultsThirty-seven participants completed the study: The difference in the positive Incremental Area Under the Curve (pIAUC) (glucose (mmol / L x h)) for half, normal and double dose ME compared with placebo was -6.1% (-18.2%, 5.9%; p = 0.316), -14.0% (-26.0%, -2.0%; p = 0.022) and -22.0% (-33.9%, -10.0%; p<0.001) respectively. The difference in the pIAUC (insulin (mIU / L x h)) for half, normal and double dose ME compared with placebo was -9.7% (-25.8%, 6.3%; p = 0.234), -23.8% (-39.9%, -7.8%; p = 0.004) and -24.7% (-40.8%, -8.6%; p = 0.003) respectively. There were no statistically significant differences between any of the 4 groups in the odds of experiencing one or more gastrointestinal symptoms (nausea, abdominal cramping, distension or flatulence).ConclusionsMulberry leaf extract significantly reduces total blood glucose rise after ingestion of maltodextrin over 120 minutes. The pattern of effect demonstrates a classical dose response curve with significant effects over placebo. Importantly, total insulin rises were also significantly suppressed over the same time-period. There were no statistically significant differences between any of the treatment groups (including placebo) in the odds of experiencing one or more gastrointestinal symptoms. Mulberry extract may have multiple modes of action and further studies are necessary to evaluate ME as a potential target for the prevention of type 2 diabetes and the regulation of dysglycaemia.

Project description:Aim/hypothesisLow-grade inflammation may contribute to obesity-related insulin resistance and has been associated with increased risk of type 2 diabetes mellitus. The present study evaluated whether treatment with salsalate, a traditional anti-inflammatory medication, would improve insulin action in obese non-diabetic individuals.MethodsThe study was a randomised, double-blind, placebo-controlled, parallel trial conducted at the inpatient clinical research unit of the NIDKK (Phoenix, AZ, USA). Participants were 54 adults (18 to 45 years of age) with BMI >or= 30 kg/m(2). The intervention was salsalate (3 g/day, n = 28) or identical placebo (n = 26) for 7 days. The allocation was kept concealed by giving the investigator only a number corresponding to a vial of placebo or salsalate sequentially randomised in blocks by sex. Main outcomes were changes in insulin action assessed as rate of glucose disposal (R (d)) by euglycaemic-hyperinsulinaemic clamp (insulin infusion rate 40 mU m(-2) min(-1)) and glucose tolerance by 75 g OGTT.ResultsThe study was completed by 47 participants, of which 40 were analysed (salsalate n = 22, placebo n = 18). Salsalate treatment resulted in decreased fasting plasma glucose concentration (mean [SD]; 4.83 [0.28] vs 5.11 [0.33] mmol/l, p = 0.001) and glucose AUC during the OGTT (p = 0.01), and in increased R (d) (20 [8] vs 18 [6] micromol [kg estimated metabolic body size](-1) min(-1), p = 0.002), while there was no significant change in these variables with placebo (p > 0.3 for all). The effect of salsalate on R (d) disappeared (p = 0.9) after normalising to increased insulin concentrations (701 [285] vs 535 [201] pmol/l, p < 0.0001) measured during the clamp. No side effects of salsalate were observed during the study.Conclusions/interpretationThe glucose-lowering potential of salicylates appears to be due to effects on insulin concentration rather than improved insulin action. Salicylate-based compounds may be useful for the treatment and prevention of type 2 diabetes.

Project description:BackgroundBlockade of the renin-angiotensin system (RAS) reduces the incidence of type 2 diabetes mellitus. In rodents, it has been demonstrated that RAS blockade improved adipose tissue (AT) function and glucose homeostasis. However, the effects of long-term RAS blockade on AT function have not been investigated in humans. Therefore, we examined whether 26-wks treatment with the angiotensin II type 1 receptor blocker valsartan affects AT function in humans with impaired glucose metabolism (IGM).Methodology/principal findingsWe performed a randomized, double-blind, placebo-controlled parallel-group study, in which 38 subjects with IGM were treated with valsartan (VAL, 320 mg/d) or placebo (PLB) for 26 weeks. Before and after treatment, an abdominal subcutaneous AT biopsy was collected for measurement of adipocyte size and AT gene/protein expression of angiogenesis/capillarization, adipogenesis, lipolytic and inflammatory cell markers. Furthermore, we evaluated fasting and postprandial AT blood flow (ATBF) ((133)Xe wash-out), systemic inflammation and insulin sensitivity (hyperinsulinemic-euglycemic clamp). VAL treatment markedly reduced adipocyte size (P<0.001), with a shift toward a higher proportion of small adipocytes. In addition, fasting (P = 0.043) and postprandial ATBF (P = 0.049) were increased, whereas gene expression of angiogenesis/capillarization, adipogenesis and macrophage infiltration markers in AT was significantly decreased after VAL compared with PLB treatment. Interestingly, the change in adipocyte size was associated with alterations in insulin sensitivity and reduced AT gene expression of macrophage infiltration markers. VAL did not alter plasma monocyte-chemoattractant protein (MCP)-1, TNF-α, adiponectin and leptin concentrations.Conclusions/significance26-wks VAL treatment markedly reduced abdominal subcutaneous adipocyte size and AT macrophage infiltration markers, and increased ATBF in IGM subjects. The VAL-induced decrease in adipocyte size was associated with reduced expression of macrophage infiltration markers in AT. Our findings suggest that interventions targeting the RAS may improve AT function, thereby contributing to a reduced risk of developing cardiovascular disease and type 2 diabetes.Trial registrationTrialregister.nl NTR721 (ISRCTN Registry: ISRCTN42786336).

Project description:Glucagon-like peptide-1 receptor agonist liraglutide may have beneficial effects on atherosclerosis development in impaired glucose tolerance (IGT). To the best of our knowledge, however, little conclusive evidence from clinical trials has been presented. The present study aimed to investigate the effect of liraglutide on atherosclerosis progression in patients with IGT. The present study was a double-blind, randomized controlled clinical trial. A total of 39 of patients aged 20-75 years who were overweight or obese (BMI, 27-40 kg/m2) and presented IGT were randomized to receive liraglutide (n=17) or lifestyle interventions (n=22) for 6 months. Serum glucose and insulin (INS) levels, lipid profile, inflammatory biomarkers and carotid intima-media thickness (CIMT) were assessed at the start and end of each treatment. Side effects were also recorded. Liraglutide treatment was found to significantly improve glycaemia, including glycosylated hemoglobin, fasting and postprandial glucose as well as INS levels (all P<0.001). Liraglutide also significantly decreased serum total cholesterol and low-density lipoprotein levels (all P<0.001). Furthermore, serum levels of inflammatory biomarkers, as well as CIMT, were decreased following liraglutide treatment compared with those in the lifestyle intervention group (all P<0.001). Kaplan-Meier analysis showed that the risk of vasculopathy in the liraglutide group was lower than that in the lifestyle intervention group (log-rank test; P=0.041). The monitoring of drug-associated side effects indicated that the dose of liraglutide (0.6 to 1.2 mg/QD via subcutaneous injection) was safe and well-tolerated. The present study suggested that liraglutide may slow atherosclerosis development and improve inflammatory status as well as intimal function in patients with IGT with few side effects. The trial was registered through the Chinese Clinical Trial Registry (ChiCTR; trial registration no. ChiCTR2200063693; retrospectively registered) on Sep 14, 2022.

Project description:BackgroundFunctional constipation (FC) is an intractable disease that carries large financial burden as well as emotional and physical stress. We aimed to assess the efficacy and safety of the newly developed smartphone-controlled vibrating capsule (VC) in patients with FC.MethodsFrom December 2018 to February 2020, we did a multicenter, blinded, placebo-controlled randomised trial in six top general hospitals in China focusing on patients aged 18 to 80 with FC. Patients were randomly assigned in a 1:1 ratio to receive VCs or placebo treatment for six weeks (two capsules per week) after a two-week baseline period. The primary outcome was the responder rate, defined as the proportion of patients with an increase of at least one complete spontaneous bowel movement (CSBM) per week during treatment compared to baseline in the full analysis set. This trial is registered with ClinicalTrials.gov, number NCT04671264, and is completed.Findings107 patients aged from 18 to 74 were randomly assigned to receive VC (n = 53) or placebo treatment (n = 54). The responder rate in the VC group was significantly higher than that in the placebo group (64·2% vs. 35·8%; difference, 27·7% [95% CI, 10·4-45·1]; P = 0·005). More patients in the VC group reported weekly CSBMs ≥ 1 for at least four weeks during treatment (difference, 22·7% [95% CI, 8-46]; P = 0·022) and follow-up period (difference, 17.3% [95% CI, 0-35]; P = 0·048). The mean Patient Assessment of Constipation-Symptoms score and Patient Assessment of Constipation-Quality of Life score differed significantly from the baseline in both groups (all P < 0·0001). The most common adverse event associated with VC was abdominal discomfort (3·7%).InterpretationVCs can promote defecation, as well as ameliorating symptoms and improving the quality of life in patients with FC with sustained efficacy. VC appears to be a potential alternative physical treatment for FC with the exact mechanism and parameters warranting further investigation.FundingThe study was supported by "One hundred leading scientists for 21st century" of Health Department of Shanghai Municipal Government (to ZL, No.2017BR005).

Dataset Information

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.

Publications

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.

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