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Open-Label Study to Assess the Efficacy of Ipragliflozin for Reducing Insulin Dose in Patients with Type 2 Diabetes Mellitus Receiving Insulin Therapy.

ABSTRACT: BACKGROUND AND OBJECTIVE:To avoid insulin-induced hypoglycemia and weight gain, the minimum dose of insulin should be used. In this study, therefore, we examined insulin dose reduction by ipragliflozin add-on therapy in Japanese patients with type 2 diabetes mellitus treated with long-acting basal insulin. METHODS:In this multicenter, open-label study, patients received one ipragliflozin 50-mg tablet once daily in combination with basal insulin for 24 weeks. The primary efficacy endpoint was the change and percent change in insulin dose from baseline to Week 24. Secondary efficacy endpoints included changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), glycoalbumin, cholesterol, leptin, adiponectin, C-peptide, glucagon, body weight, and blood pressure, and number of patients achieving withdrawal of insulin at the end of treatment (EOT). Treatment-emergent adverse events (TEAEs) were evaluated for safety. RESULTS:In total, 114 patients were screened, 103 were registered, and 97 completed the study. The mean age was 59 years and 72.8% of patients were male. The mean change in insulin dose from baseline at Week 24 was - 6.6?±?4.4 units/day (p?

SUBMITTER: Ishihara H

PROVIDER: S-EPMC6842350 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Open-Label Study to Assess the Efficacy of Ipragliflozin for Reducing Insulin Dose in Patients with Type 2 Diabetes Mellitus Receiving Insulin Therapy.

Ishihara Hisamitsu H Yamaguchi Susumu S Sugitani Toshifumi T Kosakai Yoshinori Y

Clinical drug investigation 20191201 12

<h4>Background and objective</h4>To avoid insulin-induced hypoglycemia and weight gain, the minimum dose of insulin should be used. In this study, therefore, we examined insulin dose reduction by ipragliflozin add-on therapy in Japanese patients with type 2 diabetes mellitus treated with long-acting basal insulin.<h4>Methods</h4>In this multicenter, open-label study, patients received one ipragliflozin 50-mg tablet once daily in combination with basal insulin for 24 weeks. The primary efficacy e ...[more]

PMID: 31552641

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Project description:Background and aimsInterleukin-22 has beneficial effects on inflammation and impaired hepatic regeneration that characterize alcohol-associated hepatitis (AH). F-652 is a recombinant fusion protein of human interleukin-22 and immunoglobulin G2 fragment crystallizable. This study aims to assess the safety and efficacy signals of F-652 in patients with moderate and severe AH.Approach and resultsA phase-2 dose-escalating study was carried out. F-652 (10 μg/kg, 30 μg/kg, or 45 μg/kg) administered on days 1 and 7 was tested in 3 patients each with moderate (Model for End-Stage Liver Disease [MELD] scores: 11-20) and severe AH (MELD scores: 21-28). Safety was defined by absence of serious adverse events and efficacy was assessed by Lille score, changes in MELD score, and serum bilirubin and aminotransferases at days 28 and 42. Three independent propensity-matched comparator patient cohorts were used. Plasma extracellular vesicles and multiplex serum cytokines were measured to assess inflammation and hepatic regeneration. Eighteen patients (9 moderate and 9 severe AH) were enrolled, 66% were male, and the mean age was 48 years. The half-life of F-652 following the first dose was 61-85 hours. There were no serious adverse events leading to discontinuation. The MELD score and serum aminotransferases decreased significantly at days 28 and 42 from baseline (P < 0.05). Day-7 Lille score was 0.45 or less in 83% patients as compared with 6%, 12%, and 56% among the comparator cohorts. Extracellular vesicle counts decreased significantly at day 28 (P < 0.013). Cytokine inflammatory markers were down-regulated, and regeneration markers were up-regulated at days 28 and 42.ConclusionsF-652 is safe in doses up to 45 μg/kg and associated with a high rate of improvement as determined by Lille and MELD scores, reductions in markers of inflammation and increases in markers of hepatic regeneration. This study supports the need for randomized placebo-controlled trials to test the efficacy of F-652 in AH.

Project description:IntroductionInsulin resistance syndrome and lipoatrophic diabetes are characterized by severe insulin resistance and are often refractory to treatment. Trials assessing the efficacy of antidiabetes drugs for these rare conditions have been limited, however. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, which lower glycemia independently of insulin action, have shown efficacy for type 2 diabetes with insulin resistance. We here investigated the efficacy and safety of the SGLT2 inhibitor empagliflozin for treatment of insulin resistance syndrome and lipoatrophic diabetes.MethodsThe trial was conducted at five academic centers in Japan and included seven patients with insulin resistance syndrome and one patient with lipoatrophic diabetes. Participants received 10 mg of empagliflozin daily. If the hemoglobin A1c (HbA1c) level was ≥ 7.0% (52 mmol/mol) after 12 weeks, the dose was adjusted to 25 mg. The study duration was 24 weeks, and the primary outcome was the change in HbA1c level by the end of the treatment period. Safety evaluations were performed for all participants.ResultsBy the end of the 24-week treatment period, the mean HbA1c level for all eight patients had decreased by 0.99 percentage points (10.8 mmol/mol) (95% confidence interval [CI], 0.59 to 1.38 percentage points, 6.6 to 14.9 mmol/mol) and the mean fasting plasma glucose concentration had declined by 63.9 mg/dL (3.55 mmol/L) (95% CI 25.5 to 102.3 mg/dL, 1.42 to 5.68 mmol/L). Continuous glucose monitoring revealed a reduction in mean glucose levels from 164.3 ± 76.1 to 137.6 ± 46.6 mg/dL (9.13 ± 4.23 to 7.65 ± 2.59 mmol/L) as well as an increase in the time in range (70-180 mg/dL) from 58.9 ± 36.1% to 70.8 ± 18.3%. Seventeen mild adverse events were recorded in five individuals throughout the study period. No severe events were reported. The mean body mass showed a slight decrease and the mean serum ketone body concentration showed a slight increase during treatment.ConclusionOur results demonstrate that empagliflozin shows a certain level of efficacy and safety for treatment of insulin resistance syndrome and lipoatrophic diabetes.Trial registrationjRCTs2051190029 and NCT04018365.

Project description:BACKGROUND:Glucose management is challenging in patients who require nutritional support in hospital. We aimed to assess whether fully closed-loop insulin delivery would improve glycaemic control compared with conventional subcutaneous insulin therapy in inpatients receiving enteral or parenteral nutrition or both. METHODS:We did a two-centre (UK and Switzerland), open-label, randomised controlled trial in adult inpatients receiving enteral or parenteral nutrition (or both) who required subcutaneous insulin therapy. Patients recruited from non-critical care surgical and medical wards were randomly assigned (1:1) using a computer-generated minimisation schedule (stratified by type of nutritional support [parenteral nutrition on or off] and pre-study total daily insulin dose [<50 or ≥50 units]) to receive fully closed-loop insulin delivery with faster-acting insulin aspart (closed-loop group) or conventional subcutaneous insulin therapy (control group) given in accordance with local clinical practice. Continuous glucose monitoring in the control group was masked to patients, ward staff, and investigators. Patients were followed up for a maximum of 15 days or until hospital discharge. The primary endpoint was the proportion of time that sensor glucose concentration was in target range (5·6-10·0 mmol/L), assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01774565. FINDINGS:Between Feb 8, 2018, and Sept 21, 2018, 90 patients were assessed for eligibility, of whom 43 were enrolled and randomly assigned to the closed-loop group (n=21) or the control group (n=22). The proportion of time that sensor glucose was in the target range was 68·4% [SD 15·5] in the closed-loop group and 36·4% [26·6] in the control group (difference 32·0 percentage points [95% CI 18·5-45·5; p<0·0001]). One serious adverse event occurred in each group (one cardiac arrest in the control group and one episode of acute respiratory failure in the closed-loop group), both of which were unrelated to study interventions. There were no adverse events related to study interventions in either group. No episodes of severe hypoglycaemia or hyperglycaemia with ketonaemia occurred in either study group. INTERPRETATION:Closed-loop insulin delivery is an effective treatment option to improve glycaemic control in patients receiving nutritional support in hospital. FUNDING:Diabetes UK, Swiss National Science Foundation, National Institute for Health Research Cambridge Biomedical Research Centre, Wellcome Trust, and European Foundation for the Study of Diabetes.

Project description:IntroductionTo lower the barrier for initiating insulin treatment and obtain adequate glycemic control in type 2 diabetes mellitus (T2DM), new basal insulin preparations with improved pharmacological properties and consequently a lower risk of hypoglycemia are needed. The objective of this trial was to confirm the efficacy and compare the safety of insulin degludec (IDeg) with insulin glargine (IGlar) in a multinational setting with two thirds of subjects enrolled in China.MethodsThis was a 26-week, randomized, open-label, parallel-group, treat-to-target, non-inferiority trial in 833 subjects with T2DM (48 % were female, mean age 56 years, diabetes duration 8 years), inadequately controlled on oral antidiabetic drugs (OADs). Subjects were randomized 2:1 to once-daily IDeg (555 subjects) or IGlar (278 subjects), both with metformin. The primary endpoint was the change from baseline in glycosylated hemoglobin (HbA1c) after 26 weeks.ResultsThe completion rate was high (IDeg 94.2 %; IGlar 91.4 %). Mean HbA1c decreased from 8.3 to 7.0 % in both groups. Estimated treatment difference (ETD) [95 % confidence interval (CI)] IDeg-IGlar in change from baseline was -0.05 % points [-0.18 to 0.08], confirming the non-inferiority of IDeg to IGlar. The proportion of subjects achieving HbA1c <7.0 % was 54.2 and 51.4 % with IDeg and IGlar, respectively (estimated odds ratio [95 % CI] IDeg/IGlar: 1.14 [0.84 to 1.54]). The mean decrease in fasting plasma glucose, self-measured plasma glucose profiles, and insulin dose were similar between groups. Numerically lower rates of overall (estimated rate ratio [95 % CI] IDeg/IGlar: 0.80 [0.59 to 1.10]) and nocturnal (0.77 [0.43 to 1.37]) confirmed hypoglycemia were observed with IDeg compared with IGlar. No treatment differences in other safety parameters were found. Subjects were more satisfied with the IDeg device compared with the IGlar device as reflected by the total Treatment Related Impact Measures-Diabetes Device score (ETD [95 % CI] IDeg-IGlar: 2.2 [0.2 to 4.3]).ConclusionIDeg provided adequate glycemic control non-inferior to IGlar and a tendency for a lower hypoglycemia rate. IDeg is considered suitable for initiating insulin therapy in T2DM patients on OADs requiring intensified treatment.Trial registrationClinicaltrials.gov NCT01849289.

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Dataset Information

Open-Label Study to Assess the Efficacy of Ipragliflozin for Reducing Insulin Dose in Patients with Type 2 Diabetes Mellitus Receiving Insulin Therapy.

Publications

Open-Label Study to Assess the Efficacy of Ipragliflozin for Reducing Insulin Dose in Patients with Type 2 Diabetes Mellitus Receiving Insulin Therapy.

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