Clinical trial NCT04196231: Durability of Combination of Insulin and GLP-1 Receptor Agonist or SGLT-2 Inhibitors Versus Basal Bolus Insulin Regimen in Type 2 Diabetes (BEYOND)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes
Keywords: type 2 diabetes
GLP-1RA
SGLT-2i
basal insulin
basal bolus
glycemic control
Lead sponsor: University of Campania Luigi Vanvitelli
Sponsor class: OTHER
First posted: 2019-12-12
Enrollment: 258
Sex: ALL
Minimum age (years): 35
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Hba1c change
timeFrame: 6 months, 9 months, 12 months
measure: Proportions of patients with significant HbA1c change
timeFrame: Baseline, 3 months, 6 months, 9 months, 12 months, 18 months
Secondary outcomes:
measure: Weight Change
timeFrame: Baseline, 6 months, 18 months
measure: BMI Change
timeFrame: Baseline, 6 months, 18 months
measure: Waist circumference change
timeFrame: Baseline, 6 months, 18 months
measure: Blood pressure change
timeFrame: Baseline, 6 months, 18 months
measure: Fasting glycemia change
timeFrame: Baseline, 6 months, 18 months
measure: Post-prandial glycemia change
timeFrame: Baseline, 6 months, 18 months
measure: C-peptide change
timeFrame: Baseline, 6 months, 18 months
measure: Change in total daily insulin dose
timeFrame: Baseline, 6 months, 18 months
measure: Change in lipide profile
timeFrame: Baseline, 6 months, 18 months
measure: Change in eGFR
timeFrame: Baseline, 6 months, 18 months
measure: Diabetes treatment satisfaction
timeFrame: Baseline, 6 months, 18 months
Other outcomes:
Locations:
city: Naples
country: Italy
facility: Unit of Endocrinology and Metabolic Diseases
Study officials:
affiliation: Unit of Diabetology University of Campania Luigi Vanvitelli
name: Katherine Esposito, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Unit of Endocrinology and Metabolic Diseases University of Campania Luigi Vanvitelli
name: Dario Giugliano, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Unit of Endocrinology and Metabolic Diseases University of Campania Luigi Vanvitelli
name: Giuseppe Bellastella, MD, PhD
role: STUDY_CHAIR
affiliation: Unit of Diabetology University of Campania Luigi Vanvitelli
name: Maria Ida Maiorino, MD, PhD
role: STUDY_CHAIR
References:
citation: Giugliano D, Bellastella G, Maiorino MI, Esposito K. Beyond basal-bolus insulin regimen: Is it still the ultimate chance for therapy in diabetes? Diabetes Res Clin Pract. 2019 Nov;157:107922. doi: 10.1016/j.diabres.2019.107922. Epub 2019 Nov 9. No abstract available.
citation: Giugliano D, Longo M, Caruso P, Di Fraia R, Scappaticcio L, Gicchino M, Petrizzo M, Bellastella G, Maiorino MI, Esposito K. Feasibility of Simplification From a Basal-Bolus Insulin Regimen to a Fixed-Ratio Formulation of Basal Insulin Plus a GLP-1RA or to Basal Insulin Plus an SGLT2 Inhibitor: BEYOND, a Randomized, Pragmatic Trial. Diabetes Care. 2021 Jun;44(6):1353-1360. doi: 10.2337/dc20-2623. Epub 2021 Apr 21.