Dulaglutide and Insulin MicrosecretiON in Type 1 Diabetes (DIAMOND GLP1)

Dulaglutide and Insulin MicrosecretiON in Type 1 Diabetes : A Randomized Double-blind Placebo-controlled Trial

Some patients with type 1 diabetes (T1D) can still have some remaining insulin-positive cells in the pancreas and secrete little amounts of insulin. Despite the presence of residual beta cells, the HbA1C levels remain at high levels due to functional defects of insulin secretion associated with glucotoxicity. Previous trials have indicated that treatment with a Glucagon-like peptide 1 (GLP-1 )receptor agonist in T1D with some residual beta-cell function might improve glycemic control, reduce dose of insulin and risk of hypoglycemia.

The general hypothesis of DIAMOND-GLP1 is that GLP1-R agonists will improve blood glucose

After initial screening to select insulin microsecretors and a run-in period of one month, patients will be randomized into two arms and followed in parallel for 24 weeks :

• Experimental group receiving 1.5 mg Dulaglutide s.c weekly in addition to their usual insulin regimen
• Control group receiving placebo s.c weekly in addition to their usual insulin regimen.

The primary endpoint is HbA1c value at 24 weeks

Study Overview

• Status: Completed
• Conditions: Adult Subjects With Type1Diabetes and Insulin Microsecretion
• Intervention / Treatment: Drug: Dulaglutide; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • La Tronche, France, 38700
    • Service d'Endocrinologie, Maladies Métaboliques et Nutrition, CHU Grenoble, Hopital de la Tronche
  • Montpellier 5, France, 34295
    • Département d''Endocrinologie, Diabétologie, Nutrition ; CHU Montpellier ; Hôpital Lapeyronie, Avenue du Doyen Giraud
  • NANTES cedex 1, France, 44093
    • Service d'Endocrinologie, Maladies Métaboliques et Nutrition,CHU Nantes,Hôpital Nord Laennec,Bd Jacques-Monod,Saint-Herblain
  • Paris, France, 75014
    • Service de Diabétologie et Maladies Métaboliques, Assistance Publique des Hôpitaux de Paris ;Hôpital Cochin, 27 rue du Faubourg Saint-Jacques
  • Pierre-Bénite, France, 69495
    • Service d'Endocrinologie, Diabétologie, Maladies de la Nutrition, Hospices Civils de Lyon, Centre hospitalier Lyon-Sud
  • TOULOUSE cedex 9, France, 31059
    • Service de Diabétologie Maladies Métaboliques et Nutrition ; CHU Toulouse, Pôle cardiovasculaire et métabolique, Hôpital Rangueil ; 1, avenue du Professeur Jean Poulhès - TSA 50032
  • Vandœuvre-lès-Nancy, France, 54500
    • Service de Diabétologie, Maladies Métaboliques, Nutrition ; CHU Nancy ; Technopôle Nancy-Brabois ; Rue du Morvan,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients with T1D> 4years, with age range 20-60years
• Diabetes onset after the age of 15years
• Duration of diabetes <15 years
• Treated with continuous sub-cutaneous insulin infusions (CSI) or multiple daily injections of insulin (MDI)
• Measuring their blood sugar at least four times daily
• Glycated hemoglobin (HbA1C) at screening >7 and <10%
• 16.0 kg/m2 <BMI<30.0kg/m2
• Patients with childbearing potential should use effective contraception, defined as methods with a failure rate ≤ 2 % per year (OMS 2011) during the study.
• Patients who gave its written informed consent to participate to the study
• Patients affiliated to a social insurance regime

Randomization criteria:

Patients with fasting ultra-sensitive (us) C-peptide above 15pmol/l

Exclusion Criteria:

• Patients are not eligible for this study if any of the following exclusion criteria apply:
• Patients with type 2 diabetes (T2D)
• Hypersensitivity to dulaglutide and/or any of its excipients
• Subjects with history of severe hypoglycemia or recent (< 6 months) history of diabetic ketoacidosis
• History of gastrointestinal disease with prolonged (> 3 months) nausea or vomiting, liver or kidney diseases, pancreatitis, thyroid medullary cancer or familial history of multiple endocrine neoplasia type 2
• Estimated glomerular filtration rate<60ml/min/ 1.73m2 (CKD-EPI method)
• Congestive heart failure
• Any uncontrolled disease, cancers essentially
• Chronic use of paracetamol containing products, which may falsely raise sensor glucose readings
• Use of tricyclic antidepressant, selective serotonin reuptake inhibitor, triptans, neuroleptic drugs and glucocorticoid.
• Patient who participated in another clinical trial on experimental drug in the previous 30 days
• Patients of childbearing potential who are not using adequate contraception; Female patients who are pregnant or lactating.
• Gastric bypass surgery
• Patients under guardianship

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Dulaglutide; Experimental group receiving 1.5 mg Dulaglutide subcutaneously weekly in addition to their usual insulin regimen during 24 weeks	Drug: Dulaglutide; Dulaglutide 1.5mg : One injection per week during 24 weeks
PLACEBO_COMPARATOR: placebo; Control group receiving placebo subcutaneously weekly in addition to their usual insulin regimen during 24 weeks	Drug: Placebo; Placebo: one injection per week during 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c level	Blood level	after 24 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC us C-peptide following a MMT	Evaluation and comparison before and after 24wks of treatment with Dulaglutide vs placebo the area under curve (AUC) of ultrasensitive (us) C-peptide response from 6 values following a mixed meal test (MMT)	before and after 24 weeks of treatment
Glucagon levels fasting and following a MMT	Evaluation and comparison before and after 24wks of treatment with Dulaglutide vs placebo AUC glucagon from 6 values on fasting and after MMT	before and after 24 weeks of treatment
AUC us C-peptide over AUC blood glucose levels following a MMT	Evaluation and comparison the ratio of the area under curve (AUC) of us C-peptide over the glucose response following a mixed meal test (MMT) with before and after 24 weeks of treatment Dulaglutide vs placebo	before and after 24 weeks of treatment
Daily percent times spent with continuous glucose measurements (CGM) readings between 4 and 10mmol/l, above and below this range	Evaluation and comparison the changes in the daily percent time spent with continuous glucose measurements (CGM) readings between 4 and 10mmol/l during the run-in period (1 month) and after 24 weeks with Dulaglutide vs placebo, coefficients of variation (CV) and standard deviation values (SD) as well as the average daily risk change (ADRR) of glucose values to assess blood glucose variability.	the run-in period (1 month) and after 24 weeks of treatment
Daily insulin doses and basal/ prandial ratio	Evaluation and comparison before and after 24wks of treatment with Dulaglutide vs placebo the daily insulin doses and basal/ prandial ratio	: before and after 24weeks of treatment
: Body weight		before and after 24weeks of treatment
% carbohydrates	Evaluate and compare the changes in mean carbohydrate intake during the run-in period and after 24 weeks with Dulaglutide vs placebo	the run-in period (1 month) and after 24 weeks of treatment
Number of symptomatic hypoglycemic episodes	Evaluation and comparison the number of symptomatic (both minor and severe) hypoglycemic episodes with Dulaglutide vs placebo during the study	20 months
Number of adverse events	Evaluation and comparison the number of adverse events with Dulaglutide vs placebo during the study	20 months
Autoantibodies to GAD65	Evaluation and comparison before and after 24wks of treatment the levels and subtypes of autoantibodies associated with T1D with and without dulaglutide	: before and after 24wks of treatment
insulin doses : basal/ prandial ratio	the insulin basal/ prandial ratio	before and after 24weeks of treatment
Autoantibodies to IA-2	Evaluation and comparison before and after 24wks of treatment the levels and subtypes of autoantibodies associated with T1D with and without dulaglutide	before and after 24wks of treatment
Autoantibodies to ZnT8	Evaluation and comparison before and after 24wks of treatment the levels and subtypes of autoantibodies associated with T1D with and without dulaglutide	before and after 24wks of treatment
coefficients of variation (CV)	coefficients of variation (CV) of daily percent times spent with continuous glucose measurements (CGM) readings between 4 and 10mmol/l, above and below this range .	the run-in period (1 month) and after 24 weeks of treatment

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Charles THIVOLET, Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 31, 2019
• Primary Completion (ACTUAL): February 3, 2021
• Study Completion (ACTUAL): February 3, 2021

Study Registration Dates

• First Submitted: September 11, 2018
• First Submitted That Met QC Criteria: September 11, 2018
• First Posted (ACTUAL): September 12, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 8, 2021
• Last Update Submitted That Met QC Criteria: July 7, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: type 1 diabetes; randomized; dulaglutide; insulin microsecretion; double-blind placebo-controlled trial
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Dulaglutide
• Other Study ID Numbers: 69HCL18_0047

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No