NCT04196231·Phase 4·INTERVENTIONAL

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

Lixisenatide Type 2 diabetes Completed

Status

Completed

Phase

Phase 4

Enrollment

258

Locations

Results

Not posted

Publications

Study summary

What the protocol is testing.

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.

Interventions

Treatment arms and agents.

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).

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).

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.

Timeline

From registration to results.

First posted
Dec 12, 2019
Study start
Nov 27, 2019
Primary completion
Sep 30, 2020
Study completion
Oct 20, 2020
Results posted
Not reported
Registry updated
Oct 22, 2020

Outcomes

What the study measures.

Primary outcomes

Hba1c change

Time frame · 6 months, 9 months, 12 months

HbA1c group difference at 6 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