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

Phase 4
Completed
Conditions
Type 2 Diabetes
Interventions
Drug: Insulin/Canaglifozin
Drug: Basal Bolus
Drug: Insulin/Dapaglifozin
Drug: Insulin/Empaglifozin
Registration Number
NCT04196231
Lead Sponsor
University of Campania "Luigi Vanvitelli"
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
258
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Insulin/SGLT-2iInsulin/CanaglifozinPatients 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.
Insulin/SGLT-2iInsulin/DapaglifozinPatients 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.
Insulin/SGLT-2iInsulin/EmpaglifozinPatients 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.
Basal BolusBasal BolusPatients 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
FR insulin/GLP-1RAIGlarLixiPatients 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
FR insulin/GLP-1RAIDegLiraPatients 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
Primary Outcome Measures
NameTimeMethod
Hba1c change6 months, 9 months, 12 months

HbA1c group difference at 6 months

Proportions of patients with significant HbA1c changeBaseline, 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

Secondary Outcome Measures
NameTimeMethod
Change in total daily insulin doseBaseline, 6 months, 18 months
Weight ChangeBaseline, 6 months, 18 months
BMI ChangeBaseline, 6 months, 18 months
Waist circumference changeBaseline, 6 months, 18 months
Blood pressure changeBaseline, 6 months, 18 months
Fasting glycemia changeBaseline, 6 months, 18 months
Post-prandial glycemia changeBaseline, 6 months, 18 months
C-peptide changeBaseline, 6 months, 18 months
Change in lipide profileBaseline, 6 months, 18 months

Difference between groups in total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides

Change in eGFRBaseline, 6 months, 18 months
Diabetes treatment satisfactionBaseline, 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).

Trial Locations

Locations (1)

Unit of Endocrinology and Metabolic Diseases

🇮🇹

Naples, Italy

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