Multicenter, open-label, two-arm, pilot trial for safe reduction of basal insulin dose combined with SGLT2 inhibitor in type 1 diabetes mellitus: study protocol for a RISING-STAR trial.

Abstract Background: The sodium–glucose cotransporter 2 (SGLT2) inhibitor combined with insulin is a novel therapy for type 1 diabetes mellitus. Without reducing basal insulin, hypoglycemia could occur frequently in this therapy. However, ketoacidosis is an undesirable adverse effect in patients with basal insulin reduction. The RISING-STAR study aimed to explore whether reducing the basal insulin dose combined with the SGLT2 inhibitor can safely reduce the frequency of hypoglycemia. We hypothesized that the frequency of hypoglycemia is higher if the basal insulin dose is not reduced when combined with an SGLT2 inhibitor.Methods: The study has a multicenter, open-label, two-arm design; 60 type 1 diabetes mellitus patients are being recruited from 7 hospitals. Twenty-six subjects are to be analyzed in each group for the pilot objectives. The basal insulin dose before initiating SGLT2 inhibitor combination therapy is the reference. Study subjects have been stratified into two groups based on the ratio of basal insulin daily dose (Basal) to total daily insulin dose (TDD). The subjects whose Basal/TDD ratio is < 0.4 are instructed not to reduce Basal but to reduce bolus insulin dose by 10% (group A), and subjects with a Basal/TDD ratio > 0.4 will be instructed to reduce Basal by 10% (group B). The primary outcome is the daily frequency of hypoglycemia during the intervention period (SGLT2 inhibitor administration), as determined by self-monitoring of blood glucose. We aimed to confirm a greater reduction in frequency of hypoglycemia in group B (reduced Basal), than in group A (non-reduction of Basal and reduced insulin effect levels by 10%). Baseline hypoglycemia was set at 7 ± 6 times/month. The minimum sample size required to achieve a significance of 0.05 for a one-sided t-test with a statistical power at 80% is determined. When the sample size is 26 patients in one group, the percentage increase in hypoglycemia exceeds 60%, and the sample size is considered sufficient. The secondary outcome is the frequency of ketosis pre- and post-intervention. We aimed to confirm that the frequency of ketosis did not increase in group B compared to that in group A. The frequency of adverse events, including frequency of hypoglycemia detected by flash glucose monitoring, was set as a safety endpoint.Discussion: In this pilot study, we assumed that, given a sufficient Basal, hypoglycemia would be more frequent in patients with type 1 diabetes when combined with SGLT2 inhibitors, provided the Basal was not reduced. A 10% basal insulin reduction decreased hypoglycemia but did not increase ketosis in cases where the Basal/TTD ratio was 0.4 or higher, which improves the efficacy and safety of SGLT2 inhibitor treatment in type 1 diabetes mellitus.Trial registration: Registered with Japan Registry of Clinical Trials (jRCTs051190114) on March 2, 2020. (https://rctportal.niph.go.jp/detail/jr?trial_id=jRCTs051190114)

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Multicenter, Open-Label, 2-Arm, Pilot Trial for Safe Reduction of Basal Insulin Dose Combined with SGLT2 Inhibitor in Type 1 Diabetes Mellitus: Study Protocol for a RISING-STAR Trial

Clinical Medicine Insights Endocrinology and Diabetes ◽

10.1177/11795514211040539 ◽

2021 ◽

Vol 14 ◽

pp. 117955142110405

Author(s):

Masahide Hamaguchi ◽

Yoshitaka Hashimoto ◽

Toru Tanaka ◽

Goji Hasegawa ◽

Michiyo Ishii ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus ◽

Sample Size ◽

Basal Insulin ◽

Insulin Dose ◽

Sglt2 Inhibitor ◽

Open Label ◽

Group B

Background: The safe method of instructing insulin dose reduction in combination with SGLT2 inhibitors, dapagliflozin for patients with type 1 diabetes mellitus has not been clarified. In this study, we conducted a stratified, 2-arm, parallel comparative study with the primary endpoint of decreasing the frequency of hypoglycemia by instructing basal insulin dose reduction. Methods: The study has a multicenter, open-label, 2-arm design; 60 type 1 diabetes mellitus patients are being recruited from 7 hospitals. Study subjects have been stratified into 2 groups based on the ratio of basal insulin daily dose (Basal) to total daily insulin dose (TDD). The subjects whose Basal/TDD ratio is <0.4 are instructed not to reduce Basal but to reduce bolus insulin dose by 10% (group A), and subjects with a Basal/TDD ratio >0.4 will be instructed to reduce Basal by 10% (group B). The primary outcome is the daily frequency of hypoglycemia during the intervention period (SGLT2 inhibitor administration), as determined by self-monitoring of blood glucose. We aimed to confirm a greater reduction in frequency of hypoglycemia in group B (reduced Basal), than in group A (non-reduction of Basal and reduced insulin effect levels by 10%). Baseline hypoglycemia was set at 7 ± 6 times/month. The minimum sample size required to achieve a significance of .05 for a 1-sided t-test with a statistical power at 80% is determined. When the sample size is 26 patients in 1 group, the percentage increase in hypoglycemia exceeds 60%, and the sample size is considered sufficient. Discussion: In this pilot study, we assumed that, given a sufficient Basal, hypoglycemia would be more frequent in patients with type 1 diabetes when combined with SGLT2 inhibitors, provided the Basal was not reduced.

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Multicenter, open-label, two-arm pilot trial for safety reduction of basal insulin dose combined with SGLT2 inhibitor in type 1 diabetes mellitus: A study protocol for RISING-STAR

10.21203/rs.3.rs-52292/v2 ◽

2020 ◽

Author(s):

Masahide Hamaguchi ◽

Yoshitaka Hashimoto ◽

Toru Tanaka ◽

Goji Hasegawa ◽

Michiyo Ishii ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus ◽

Sample Size ◽

Basal Insulin ◽

Insulin Dose ◽

Sglt2 Inhibitor ◽

Open Label ◽

Group B

Abstract Background SGLT2 inhibitor combined with insulin is a novel therapy for patients with type 1 diabetes mellitus. Without the reduction of basal insulin, hypoglycemia could occur frequently in this therapy. However, ketoacidosis is an undesirable adverse effect in cases with basal insulin reduction. Methods This was a multicenter, open-label, two-arm study. Sixty subjects with type 1 diabetes mellitus were recruited from 7 hospitals. Subjects whose basal insulin daily dose to total daily insulin dose (TDD) ratio was < 0.4 were instructed not to reduce the basal insulin dose but to reduce the bolus insulin dose by 10% (Group A), and subjects with a basal-to-TDD ratio > 0.4 were instructed to reduce the basal insulin dose by 10% (Group B). We hypothesized that the frequency of hypoglycemia would be reduced in Group B. The primary outcome was the frequency of hypoglycemia per day during the intervention period (administration of SGLT2 inhibitor) as determined by self-monitoring of blood glucose (SMBG). The baseline number of hypoglycemic attacks was set at 7 ± 6 times/month. The minimum sample size required to achieve a significance of 0.05 for a one-sided t-test with a statistical power of 80% was determined. When the sample size was 26 patients in one group, the percent increase in hypoglycemia was more than 60%; thus, the sample size was estimated to be sufficient. The secondary outcome was the frequency of ketosis before and after the intervention. We aimed to confirm that the frequency of ketosis does not increase in Group B compared with Group A. The frequency of adverse events, including the frequency of hypoglycemia detected using flash glucose monitoring (FGM), was set as the safety endpoint. Discussion The RISING-STAR study will contribute results from a two-arm randomized trial in which a reduction in basal insulin dose is indicated or no reduction in basal insulin dose is instructed for concomitant use of SGLT2 inhibitors in patients with type 1 diabetes to prevent the development of hypoglycemia.Trial registration Registered with the Japan Registry of Clinical Trials (jRCTs051190114) on March 2, 2020.

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Multicenter, Open-Label, Two-Arm, Pilot Trial for Safety Reduction of Basal Insulin Dose Combined with SGLT2 Inhibitor in Type 1 Diabetes Mellitus: Study Protocol for RISING-STAR.

10.21203/rs.3.rs-52292/v1 ◽

2020 ◽

Author(s):

Masahide Hamaguchi ◽

Yoshitaka Hashimoto ◽

Toru Tanaka ◽

Goji Hasegawa ◽

Michiyo Ishii ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus ◽

Basal Insulin ◽

Insulin Dose ◽

Sglt2 Inhibitor ◽

Daily Insulin ◽

Daily Insulin Dose ◽

Daily Dose

Abstract Background: SGLT2 inhibitor combined with insulin therapy is a novel therapy for patients with type 1 diabetes mellitus. Without the reduction of basal insulin, hypoglycemia could occur frequently in this therapy. But diabetic ketoacidosis is an undesirable adverse effect in case with basal insulin reduction. The aim of this study is to explore whether the reduction of the basal insulin dose combined with SGLT2 inhibitor in patients with type 1 diabetes mellitus can reduce the frequency of hypoglycemia and be used safely. We hypothesized that with an adequate basal insulin dose, the frequency of hypoglycemia is higher if the basal insulin dose is not reduced when combined with SGLT2 inhibitor.Methods and Analysis: The study has a two-arm design; 60 subjects with type 1 diabetes mellitus are being recruited from 7 hospitals. The basal insulin dose before the start of the SGLT2 inhibitor combination therapy is the reference. Study subjects are stratified into two groups based on the ratio of basal insulin daily dose (Basal) to total daily insulin dose (TDD). The subjects are instructed to reduce the basal insulin dose by 10% or 0% for Basal to TDD ratio of <0.4 and > 0.4, respectively.The primary outcome is the frequency of hypoglycemia per day during the intervention period (administration of SGLT2 inhibitor) as determined by self-monitoring of blood glucose (SMBG). The secondary outcome is the frequency of ketosis before and after the intervention. Discussion: 10% basal insulin reduction could reduce hypoglycemia as well as could not increase ketosis in case that the ratio of basal insulin daily dose to total daily insulin dose is 0.4 or higher, which improve the efficacy and safety of SGLT2 inhibitor treatment patients with type 1 diabetes mellitus.Ethics and Dissemination: The study was approved by Kyoto Prefectural University of Medicine, Clinical Research Review Board (CRB5180001). The results will be disseminated through presentations at appropriate conferences and meetings, and published in peer-reviewed journals.Trial registration: Registered with Japan Registry of Clinical Trials (jRCTs051190114) on 2 March, 2020. https://rctportal.niph.go.jp/detail/jr?trial_id=jRCTs051190114)

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Relationship of C-peptide levels to duration of Type 1 diabetes – A study from Sindh, Pakistan

Pakistan Journal of Medical Sciences ◽

10.12669/pjms.36.4.1531 ◽

2020 ◽

Vol 36 (4) ◽

Author(s):

Asher Fawwad ◽

Nazish Waris ◽

Saima Askari ◽

Graham Ogle ◽

Muhammad Yakoob Ahmedani ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus ◽

Diabetes Group ◽

C Peptide ◽

Duration Of Diabetes ◽

Group A ◽

Group B ◽

Relationship Of

Objective: To determine the relationship of C-peptide levels with duration of type 1 diabetes mellitus. Methods: This prospective study was conducted at Baqai Institute of Diabetology and Endocrinology (BIDE), Baqai Medical University (BMU), Karachi-Pakistan from December 2013 to December 2015. A total of 184 subjects were recruited during the study period, 100 in Group-A and 84 in Group-B. Subjects clinically diagnosed with type 1 diabetes Mellitus (T1DM) were categorized into two groups based on duration of diabetes: Group-A (with ≤1-year duration of diabetes) and Group-B (with >1-year duration of diabetes). Ninety-nine of the 100 enrolled subjects in Group-A were diagnosed as having T1DM, with one subject who presented at 11.9 years of age and diagnosed with T2DM excluded from this study. Blood samples were drawn for biochemical parameters. Data for baseline characteristics and clinical parameters (HbA1c and C-peptide) were obtained from hospital management system of BIDE. Results: Fifty-seven (57.6%) subjects in Group-A, and 39 (46.4%) in Group-B were males. Mean±SD duration of diabetes (years) was 0.64±0.6 (range 0-1) in Group-A, and 7.65±5.5 (range 1-23) in Group-B. Family history of T1DM and T2DM was 1(1%) and 27(27.3%) in Group-A, and 8(9.52%) and 21(25%) in Group-B, respectively. Twenty-one (21.2%) subjects presented in diabetic ketoacidosis (DKA) in Group-A and 18(21.4%), in Group-B. Mean±SD for HbA1c was non-significantly higher in Group-A 11.12±2.31 compared to Group-B 10.42±1.45. Mean±SD for C-peptide was 1.91±1.53 ng/mL (0.60±0.481 nmol/L) in Group-A, and 1.82±1.01 (0.57±0.32 nmol/L) in Group-B (p=0.984). Conclusion: The study found that subjects with longer duration of T1DM had non-significantly decreased C-peptide levels compared to a group in which C-peptide was measured at or soon after diagnosis. Furthermore, C-peptide levels in many subjects with longer duration were higher than expected in classic T1DM. doi: https://doi.org/10.12669/pjms.36.4.1531 How to cite this:Fawwad A, Waris N, Askari S, Ogle G, Ahmedani MY, Basit A. Relationship of C-peptide levels to duration of Type 1 diabetes – A study from Sindh, Pakistan. Pak J Med Sci. 2020;36(4):---------. doi: https://doi.org/10.12669/pjms.36.4.1531 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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