scholarly journals The SimpliciT1 Study: A Randomized, Double-Blind, Placebo-Controlled Phase 1b/2 Adaptive Study of TTP399, a Hepatoselective Glucokinase Activator, for Adjunctive Treatment of Type 1 Diabetes

2021 ◽  
Author(s):  
Klara R. Klein ◽  
Jennifer L. R. Freeman ◽  
Imogene Dunn ◽  
Chris Dvergsten ◽  
M. Sue Kirkman ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Glycemic Control ◽  
Controlled Trial ◽  
Adjunctive Treatment ◽  
Study Phase ◽  
Double Blind ◽  
Glucokinase Activator ◽  
Phase 1B ◽  
The Difference

<b>Objective</b> <p>Despite advances in exogenous insulin therapy, many patients with type 1 diabetes do not achieve acceptable glycemic control and remain at risk for ketosis and insulin-induced hypoglycemia. We conducted a randomized controlled trial to determine whether TTP399, a novel hepatoselective glucokinase activator, improved glycemic control in people with type 1 diabetes without increasing hypoglycemia or ketosis. </p> <p><b>Research design and methods</b></p> <p>SimpliciT1 was a Phase 1b/2 adaptive study. Phase 2 activities were conducted in 2 parts. Part 1 randomized 20 participants using continuous glucose monitors (CGM) and continuous subcutaneous insulin infusion (CSII). Part 2 randomized 85 participants on multiple daily injections of insulin or CSII. In both Part 1 and 2, participants were randomized to TTP399 800 mg or matched placebo (fully blinded) and treated for 12-weeks. The primary endpoint was the change in HbA1c from baseline to week 12.</p> <p><b>Results</b></p> <p>The difference in the change in HbA1c from baseline to week 12 between TTP399 and placebo was -0.7% (95% CI -1.3, -0.07) in Part 1 and -0.21 (95% CI -0.39, -0.04) in Part 2. Despite a greater decrease in HbA1c with TTP399, the frequency of severe or symptomatic hypoglycemia decreased by 40% relative to placebo in Part 2. In both Part 1 and Part 2, plasma beta-hydroxybutrate and urinary ketones were lower during treatment with TTP399 than placebo. </p> <p><b>Conclusions</b></p> <p>TTP399 lowers HbA1c and reduces hypoglycemia without increasing the risk of ketosis and should be further evaluated as an adjunctive therapy for the treatment of type 1 diabetes.</p>

scholarly journals The SimpliciT1 Study: A Randomized, Double-Blind, Placebo-Controlled Phase 1b/2 Adaptive Study of TTP399, a Hepatoselective Glucokinase Activator, for Adjunctive Treatment of Type 1 Diabetes

2021 ◽  
Author(s):  
Klara R. Klein ◽  
Jennifer L. R. Freeman ◽  
Imogene Dunn ◽  
Chris Dvergsten ◽  
M. Sue Kirkman ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Glycemic Control ◽  
Controlled Trial ◽  
Adjunctive Treatment ◽  
Study Phase ◽  
Double Blind ◽  
Glucokinase Activator ◽  
Phase 1B ◽  
The Difference

<b>Objective</b> <p>Despite advances in exogenous insulin therapy, many patients with type 1 diabetes do not achieve acceptable glycemic control and remain at risk for ketosis and insulin-induced hypoglycemia. We conducted a randomized controlled trial to determine whether TTP399, a novel hepatoselective glucokinase activator, improved glycemic control in people with type 1 diabetes without increasing hypoglycemia or ketosis. </p> <p><b>Research design and methods</b></p> <p>SimpliciT1 was a Phase 1b/2 adaptive study. Phase 2 activities were conducted in 2 parts. Part 1 randomized 20 participants using continuous glucose monitors (CGM) and continuous subcutaneous insulin infusion (CSII). Part 2 randomized 85 participants on multiple daily injections of insulin or CSII. In both Part 1 and 2, participants were randomized to TTP399 800 mg or matched placebo (fully blinded) and treated for 12-weeks. The primary endpoint was the change in HbA1c from baseline to week 12.</p> <p><b>Results</b></p> <p>The difference in the change in HbA1c from baseline to week 12 between TTP399 and placebo was -0.7% (95% CI -1.3, -0.07) in Part 1 and -0.21 (95% CI -0.39, -0.04) in Part 2. Despite a greater decrease in HbA1c with TTP399, the frequency of severe or symptomatic hypoglycemia decreased by 40% relative to placebo in Part 2. In both Part 1 and Part 2, plasma beta-hydroxybutrate and urinary ketones were lower during treatment with TTP399 than placebo. </p> <p><b>Conclusions</b></p> <p>TTP399 lowers HbA1c and reduces hypoglycemia without increasing the risk of ketosis and should be further evaluated as an adjunctive therapy for the treatment of type 1 diabetes.</p>

scholarly journals Effect of the GLP-1 Receptor Agonist Exenatide on Impaired Awareness of Hypoglycemia in Type 1 Diabetes: A Randomized Controlled Trial

2019 ◽  
Vol 104 (9) ◽  
pp. 4143-4150 ◽  
Author(s):  
Lian A van Meijel ◽  
Hanne M Rooijackers ◽  
Cees J Tack ◽  
Bastiaan E de Galan
Keyword(s):  
Type 1 Diabetes ◽  
Controlled Trial ◽  
Glucose Variability ◽  
Glucose Sensors ◽  
Adjunctive Treatment ◽  
Double Blind ◽  
Glucose Levels ◽  
Impaired Awareness ◽  
Glucagon Like Peptide 1

Abstract Context Impaired awareness of hypoglycemia (IAH), resulting from habituation to recurrent hypoglycemia, can be reversed by strict avoidance of hypoglycemia. Adjunctive treatment with glucagon-like peptide-1 receptor agonists may reduce glucose variability, hence lower the risk of hypoglycemia and improve awareness. The aim of our study was to investigate the effect of exenatide on awareness of hypoglycemia in patients with type 1 diabetes and IAH. Methods This was a randomized double-blind, placebo-controlled crossover trial. Ten patients with type 1 diabetes and IAH were included [age, 38.5 ± 4.4 years; 40% males; glycated hemoglobin 7.2% ± 0.4% (55.2 ± 4.8 mmol/mol)]. Patients were treated with exenatide 5 µg twice daily (first two weeks), followed by 10 µg twice daily (remaining four weeks) or matching placebo, with a four-week washout period. Patients wore blinded glucose sensors in the final weeks and modified hyperinsulinemic normoglycemic-hypoglycemic glucose clamps (nadir 2.5 mmol/L) were performed at the end of each treatment period. Results Treatment with exenatide caused body weight to decrease compared with placebo (−3.9 ± 0.9 vs 0.6 ± 1.2 kg, P = 0.047). Exenatide did not change mean 24-hour glucose levels (8.3 ± 0.4 vs 8.5 ± 0.3 mmol/L, exenatide vs placebo, P = 0.64), median (interquartile range) percentage of time spent in hypoglycemia [15.5 (4.5, 25.5) vs 7.8 (4.4, 17.1)%, P = 0.11] and frequency of hypoglycemia (15.8 ± 3.7 vs 12.1 ± 3.5, P = 0.19). Symptom scores in response to clamped hypoglycemia were similar between exenatide [median change 1.0 (−1.5, 7.0)] and placebo [4.5 (1.5, 5.8), P = 0.08]. Conclusions Six weeks of treatment with exenatide did not improve awareness of hypoglycemia in patients with type 1 diabetes and IAH.

236-OR: Volagidemab, a Human Glucagon Receptor Antagonist, Improves Glycemic Control in Subjects with Type 1 Diabetes (T1D): A 12-Week, Randomized, Double-Blind, Placebo-Controlled Trial

Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 236-OR
Author(s):  
JEREMY PETTUS ◽  
SCHAFER C. BOEDER ◽  
MARK P. CHRISTIANSEN ◽  
DOUGLAS S. DENHAM ◽  
TIMOTHY S. BAILEY ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Glycemic Control ◽  
Receptor Antagonist ◽  
Controlled Trial ◽  
Double Blind ◽  
Glucagon Receptor ◽  
Double Blind Placebo ◽  
Glucagon Receptor Antagonist

scholarly journals Feasibility study of real-time online text-based CBT to support self-management for people with type 1 diabetes: the Diabetes On-line Therapy (DOT) Study

2021 ◽  
Vol 9 (1) ◽  
pp. e001934
Author(s):  
Anne M Doherty ◽  
Anne Herrmann-Werner ◽  
Arann Rowe ◽  
Jennie Brown ◽  
Scott Weich ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Glycemic Control ◽  
Real Time ◽  
Instant Messaging ◽  
Controlled Trial ◽  
Self Management ◽  
Diabetes Distress ◽  
The Mean ◽  
Distress Scale

IntroductionThis study examines the feasibility of conducting diabetes-focused cognitive–behavioral therapy (CBT) via a secure online real-time instant messaging system intervention to support self-management and improve glycemic control in people with type 1 diabetes.Research design and methodsWe used a pre–post uncontrolled intervention design over 12 months. We recruited adults with type 1 diabetes and suboptimal glycemic control (HbA1c ≥69 mmol/mol (DCCT 8.5%) for 12 months) across four hospitals in London. The intervention comprised 10 sessions of diabetes-focused CBT delivered by diabetes specialist nurses. The primary outcomes were number of eligible patients, rates of recruitment and follow-up, number of sessions completed and SD of the main outcome measure, change in HbA1c over 12 months. We measured the feasibility of collecting secondary outcomes, that is, depression measured using Patient Health Questionnaire-9 (PHQ-9), anxiety measured Generalised Anxiety Disorder (GAD) and the Diabetes Distress Scale (DDS).ResultsWe screened 3177 patients, of whom 638 were potentially eligible, from whom 71 (11.1%) were recruited. The mean age was 28.1 (13.1) years, and the mean HbA1c was 84.6 mmol/mol (17.8), DCCT 9.9%. Forty-six (65%) patients had at least 1 session and 29 (41%) completed all sessions. There was a significant reduction in HbA1c over 12 months (mean difference −6.2 (2.3) mmol/mol, DCCT 0.6%, p=0.038). The change scores in PHQ-9, GAD and DDS also improved.ConclusionsIt would be feasible to conduct a full-scale text-based synchronized real-time diabetes-focused CBT as an efficacy randomized controlled trial.

scholarly journals Liraglutide accelerates colonic transit in people with type 1 diabetes and polyneuropathy: A randomised, double‐blind, placebo‐controlled trial

2020 ◽  
Vol 8 (6) ◽  
pp. 695-704
Author(s):  
Anne‐Marie Langmach Wegeberg ◽  
Christian Stevns Hansen ◽  
Adam D Farmer ◽  
Jesper Scott Karmisholt ◽  
Asbjorn M Drewes ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Controlled Trial ◽  
Colonic Transit ◽  
Double Blind ◽  
Double Blind Placebo

scholarly journals Effect of 6 Months of Flash Glucose Monitoring in Youth With Type 1 Diabetes and High-Risk Glycemic Control: A Randomized Controlled Trial

Diabetes Care ◽  
2020 ◽  
Vol 43 (10) ◽  
pp. 2388-2395 ◽  
Author(s):  
Sara E. Boucher ◽  
Andrew R. Gray ◽  
Esko J. Wiltshire ◽  
Martin I. de Bock ◽  
Barbara C. Galland ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Type 1 Diabetes ◽  
High Risk ◽  
Glycemic Control ◽  
Controlled Trial ◽  
Glucose Monitoring ◽  
Flash Glucose Monitoring ◽  
Randomized Controlled
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