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

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.

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