Durability of Combination of Insulin and GLP-1 Receptor Agonist or SGLT-2 Inhibitors Versus Basal Bolus Insulin Regimen in Type 2 Diabetes (BEYOND) (BEYOND)

October 20, 2020 updated by: Katherine Esposito, University of Campania "Luigi Vanvitelli"

Durability of Combination of Insulin and GLP-1 Receptor Agonist or SGLT-2 Inhibitors Versus Basal Bolus Insulin Regimen in Type 2 Diabetes: a Randomized Controlled Trial

BEYOND represents an open-label, parallel, three-arm randomized controlled trial, aimed at evaluating the effects of combination therapy of fixed ratio basal insulin/GLP-1 receptor agonist (GLP-1RA) or basal insulin/SGLT-2 inhibitors (SGLT-2i) on the durability of the glycemic control, as compared with the basal bolus insulin regimen, in people with type 2 diabetes failing to achieve glycemic targets with injective therapy. The potential benefits for participants in the study include the possibility of improving the glyco-metabolic control with drugs that have been evaluated as safe and protective for the heart and the kidneys. The primary outcome of the study is the mean HbA1c change between groups at six months. Participants in the study will be followed for subsequent 18 months in order to evaluate the durability of glycemic control and the chenge of other secondary outcomes.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
258

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Naples, Italy, 80138
        • Unit of Endocrinology and Metabolic Diseases

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

35 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Poor glycemic control (HbA1c ≥7.5%)
  • Stable basal bolus insulin regimen for almost a year, eventually associated with metformin.

Exclusion Criteria:

  • Type 1 diabetes or secondary diabetes;
  • Previous treatment for the last three months with GLP-1RA or DPP-4 inhibitors;
  • Hypersensitivity towards active substances or other ingredients of the drugs used in the study
  • Participation in other trial with experimental drugs within 30 days
  • Diseases that represent contraindication to GLP-1RA use (pancreatitis, gallstones)
  • Pregnancy or planned pregnancy within the time of the study
  • Serum creatinine > 1,3 mg/dL in women and >1,4 mg/dL in men
  • eGFR < 30 mL/min
  • Previous cancer or antineoplastic therapy for five years before randomization
  • Current therapy with glucocorticoid (oral, topic or sistemic administration) or with antypsichotic drugs
  • Previous ketoacidosis
  • Any clinical, psychologic or psychiatric condition that is incompatible with the study according to the investigator

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
ACTIVE_COMPARATOR: FR insulin/GLP-1RA
Patients in this arm will receive one of these fixed ratio combo of insulin and GLP-1RAs, according to the current clinical practice and the drugs' data sheet: IDegLira or IGlarLixi
Drug: IDegLira
IDegLira will be started at 16 dose steps (16 U insulin degludec plus 0.58 mg liraglutide, once daily). On the basis of prebreakfast self-monitored blood glucose measurements doses of IDegLira will be titrated individually twice per week to achieve a prebreakfast plasma glucose of 80-130 mg/dL by use of an algorithm (adding 2 dose steps for prebreakfast plasma glucose >130 mg/dL; no dose change for prebreakfast plasma glucose of 80-130 mg/dL; reducing 2 dose steps for prebreakfast plasma glucose < 80 mg/dL). The daily dose of IDegLira could be titrated to 50 dose steps (50 U insulin degludec plus 1.8 mg liraglutide).
Drug: IGlarLixi
IGlarLixi will be started at 10 dose steps (10 U insulin glargine plus 5 mcg lixisenatide, once daily). On the basis of prebreakfast self-monitored blood glucose measurements, doses of IGlarLixi will be titrated individually once per week to achieve a prebreakfast plasma glucose of 80-130 mg/dL by use of an algorithm (adding 2 dose steps for prebreakfast plasma glucose >130 mg/dL; no dose change for prebreakfast plasma glucose of 80-130 mg/dL; reducing 2 dose steps for prebreakfast plasma glucose < 80 mg/dL). The daily dose of IGlarLixi could be titrated to 60 dose steps (60 U insulin degludec plus 20 mcg lixisenatide).
ACTIVE_COMPARATOR: Insulin/SGLT-2i
Patients in this arm will receive the basal insulin used before the randomization and one of these SGLT-2i according to the current clinical practice and the drugs' data sheet: canagliflozin, dapagliflozin or empagliflozin.
Drug: Insulin/Canaglifozin
Patients in this arm will continue the basal insulin used before the randomization, with dosage titration on the basis of the following algorithm: adding 2 units for prebreakfast plasma glucose >130 mg/dL; no dose change for prebreakfast plasma glucose of 80-130 mg/dL; reducing 2 units for prebreakfast plasma glucose < 80 mg/dL. Moreover, they will be assigned to canaglifozin, according to the current clinical practice and the drugs' data sheet. Canagliflozin will be started at 100 mg daily per oral administration, and augmented to 300 mg/per day if required (HbA1c >7.5 after 12 weeks).
Drug: Insulin/Dapaglifozin
Patients in this arm will continue the basal insulin used before the randomization, with dosage titration on the basis of the following algorithm: adding 2 units for prebreakfast plasma glucose >130 mg/dL; no dose change for prebreakfast plasma glucose of 80-130 mg/dL; reducing 2 units for prebreakfast plasma glucose < 80 mg/dL. Moreover, they will be assigned to dapaglifozin, according to the current clinical practice and the drugs' data sheet. Dapagliflozin will be started at 10 mg daily per oral administration
Drug: Insulin/Empaglifozin
Patients in this arm will continue the basal insulin used before the randomization, with dosage titration on the basis of the following algorithm: adding 2 units for prebreakfast plasma glucose >130 mg/dL; no dose change for prebreakfast plasma glucose of 80-130 mg/dL; reducing 2 units for prebreakfast plasma glucose < 80 mg/dL. Moreover, they will be assigned to empaglifozin, according to the current clinical practice and the drugs' data sheet. Empagliflozin will be started at 10 mg daily per oral administration, and augmented to 25 mg/per day if required (HbA1c >7.5 after 12 weeks).
ACTIVE_COMPARATOR: Basal Bolus
Patients in this arm will receive a basal insulin (glargine, glargine-300 or degludec) at bed-time plus 3 injections of a short-acting insulin analogue (aspart, lispro or glulisine) before meals
Drug: Basal Bolus
Patients in this arm will continue the basal insulin (glargine, degludec or glargine-300) used before the randomization. The insulin titration will be guided by the medical staff, according to the following algorithm: adding 2 units of basal insulin for prebreakfast plasma glucose >130 mg/dL; no dose change for prebreakfast plasma glucose of 80-130 mg/dL; reducing 2 units of basal insulin for prebreakfast plasma glucose < 80 mg/dL. The short acting insulin analogue (lispro, aspart or glulisine) will be started at the dosage of 4 units before meals (3 times per day) and will be titrated twice a week until achieving pre-prandial glucose values ranging from 80-130 mg/dL.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Hba1c change
Time Frame: 6 months, 9 months, 12 months
HbA1c group difference at 6 months
6 months, 9 months, 12 months
Proportions of patients with significant HbA1c change
Time Frame: Baseline, 3 months, 6 months, 9 months, 12 months, 18 months
Proportions of patients undergoing a reduction equal or higher than 0.5% as compared with baseline levels during the follow up
Baseline, 3 months, 6 months, 9 months, 12 months, 18 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Weight Change
Time Frame: Baseline, 6 months, 18 months
Baseline, 6 months, 18 months
BMI Change
Time Frame: Baseline, 6 months, 18 months
Baseline, 6 months, 18 months
Waist circumference change
Time Frame: Baseline, 6 months, 18 months
Baseline, 6 months, 18 months
Blood pressure change
Time Frame: Baseline, 6 months, 18 months
Baseline, 6 months, 18 months
Fasting glycemia change
Time Frame: Baseline, 6 months, 18 months
Baseline, 6 months, 18 months
Post-prandial glycemia change
Time Frame: Baseline, 6 months, 18 months
Baseline, 6 months, 18 months
C-peptide change
Time Frame: Baseline, 6 months, 18 months
Baseline, 6 months, 18 months
Change in total daily insulin dose
Time Frame: Baseline, 6 months, 18 months
Baseline, 6 months, 18 months
Change in lipide profile
Time Frame: Baseline, 6 months, 18 months
Difference between groups in total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides
Baseline, 6 months, 18 months
Change in eGFR
Time Frame: Baseline, 6 months, 18 months
Baseline, 6 months, 18 months
Diabetes treatment satisfaction
Time Frame: Baseline, 6 months, 18 months
In order to measure satisfaction with diabetes treatment regimens, we used the self-reported Diabetes Treatment Satisfaction Questionnaire. This instrument aims to assess levels of satisfaction in subjects using different treatment strategies. The questionnaire consists of eight questions: six questions addresses general satisfaction with a score from 0 to 6 for each question (0 = worst), that has to be computed in a total score ranging from 0 (=worst) to 36 (=best); among the remaining two questions, which has to be computed separately as two subscales, one concerns the perception of hyperglycemic events and another the perception of hypoglycemic events, both with a score from 0 (none of the time) to 6 (most of the time).
Baseline, 6 months, 18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Campania "Luigi Vanvitelli"

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Katherine Esposito, MD, PhD, Unit of Diabetology University of Campania Luigi Vanvitelli
  • Principal Investigator: Dario Giugliano, MD, Unit of Endocrinology and Metabolic Diseases University of Campania Luigi Vanvitelli
  • Study Chair: Giuseppe Bellastella, MD, PhD, Unit of Endocrinology and Metabolic Diseases University of Campania Luigi Vanvitelli
  • Study Chair: Maria Ida Maiorino, MD, PhD, Unit of Diabetology University of Campania Luigi Vanvitelli

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 27, 2019

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 30, 2020

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 20, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 6, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 11, 2019

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 12, 2019

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 22, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 20, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BEYOND Protocol

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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