Relationship Between Improvement in Insulin Secretion and Decrease in HbA1c in GLP-1 RA Therapy in T2DM Patients

NCT04135287 | Unknown Phase 4

• 1 other identifier: RA HM-2019-004
• Study Type: interventional
• Target: 315
• Locations: 1 country
• Sites: 1

Brief Summary

GLP-1 receptor agonists (GLP-1 RA) is group of antidiabetic agents very effective in lowering the plasma glucose concentration in T2DM patients . Currently there are several agents approved for the treatment of T2DM which are classified into two groups: (1) short acting GLP-1 RA and include exenatide BID and lexisenatide, and (2) long acting agents which are given once daily or weekly injection and include liraglutide, semaglutide, dulaglutide and budyreon . Clinical studies have demonstrated that long acting GLP-1 RA (e.g. liraglutide, bydureon and dulaglutide) produce \~1.5% reduction in the HbA1c , which was significantly greater than that caused by other classes of antidiabetic agents (e.g. DPP4 inhibitors, and SGLT2 inhibitors). Members of this class of drugs exert multiple metabolic actions in T2DM. They potentiate insulin-stimulated insulin secretion from the beta cell , inhibit glucagon secretion from the alpha cells and inhibit appetite and promote weight loss. Together, these metabolic actions of GLP-1 RA contribute to the improvement in glucose metabolism and decrease in HbA1c. Although GLP-1 RA produce a robust mean decrease in HbA1c (\~1.5%), the magnitude of decrease in HbA1c in the individual patient vary considerably. Clinical studies showed that approximately one third of T2DM patients receiving GLP-1 RA experience very modest to no decrease in the HbA1c while another third of patients experience a robust decrease in the HbA1c. the reason for this large variability in the individual response to GLP-1 RA is unknown. Studies which attempted to identify possible clinical predictors that distinguish between "good responders" and "poor responders" have failed to identify clinical parameter that can predict the magnitude of decrease in HbA1c by GLP-1 RA in T2DM patients. Because of the central role of beta cell function in the regulation of plasma glucose concentration, the study investigators hypothesis that varying degree of beta cell response to GLP-1 RA action is the principal factor responsible for the large variability in the decrease in HbA1c by GLP-1 RA. The aim of the present study is to test this hypothesis.

Conditions

Diabetes Mellitus, Type 2

Keywords

GLP-1 RA

Outcome Measures

Primary Outcomes (1)

• HbA1c

  Change in HbA1c from baseline to 6 months

  6 months

Secondary Outcomes (3)

• Beta cell function

  6 months

• Weight loss

  6 months

• Fasting Plasma Glucagon

  6 months

Study Arms (1)

Arm 1

EXPERIMENTAL

Treatment with GLP-1 RA

Drug: GLP-1 receptor agonist

Interventions

GLP-1 receptor agonist DRUG

The main objective of the study is to determine the relationship between the increase in glucose-stimulated insulin secretion and decrease in HbA1c caused by GLP-1 RA therapy in poorly controlled T2DM patients. We also will identify a cut point of an increase in beta cell function which produces a clinically meaningful decrease in HbA1c.

Arm 1

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age 21-75 years
• BMI=18-45 kg/m2
• HbA1c \>7.% and \<14.0%
• Subjects must be on stable antihyperglycemic therapy during the 3 months prior to enrolment.
• Good general health as determined by physical exam, medical history, blood chemistries, CBC, TSH, T4, lipid profile.
• Stable body weight (± 3 lbs) over the preceding three months
• Not participate in an excessively heavy exercise program.

You may not qualify if:

• Subjects receiving therapy with GLP-1 RA or received in the past 3 months. Subjects who received GLP-1 therapy \> 3 months prior to the study are eligible to participate if their body weight has returned to the pretreatment level.
• Subjects receiving DPP4 inhibitors or who received DPP4 inhibitor in the 3 month preceding the study. Subjects on DPP4 inhibitors who are interested in switching therapy to GLP-1 RA must have 3 months washout period.
• Haematocrit \< 32.0
• history of thyroid cancer or pancreatitis,
• Creatinine \> 1.5 mg/dl,
• history of malignant disease,
• Pregnancy.
• Congestive heart failure

Sponsors & Collaborators

• Dasman Diabetes Institute: lead

Study Sites (1)

Dasman Diabetes Institute

Kuwait City, 15462, Kuwait

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Ebaa AlOzairi, MD, PhD

  Dasman Diabetes Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ebaa AlOzairi, Md, PhD

CONTACT

+965 22242999; ebaa.alozairi@dasmaninstitute.org

Smitha Abraham

CONTACT

+965 22260005; smitha.abraham@dasmaninstitute.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Medical Officer

Model Details: Subjects will be randomized to receive for 6 months in an open label fashion GLP1RA

Study Record Dates

• First Submitted: October 20, 2019
• First Posted: October 22, 2019
• Study Start: March 1, 2020
• Primary Completion: March 1, 2023
• Study Completion: July 15, 2023
• Last Updated: July 21, 2020

Record last verified: 2020-07

Locations

KU (1)