Basal insulin intensification with GLP-1RA and dual GIP and GLP-1RA in patients with uncontrolled type 2 diabetes mellitus: A rapid review of randomized controlled trials and meta-analysis

Tirzepatide, a dual agonist of Glucose-Dependent Insulinotropic Polypeptide (GIP) and Glucagon-Like Peptide 1 (GLP-1) receptors, improved glucose control and reduced body weight in different therapeutic approaches. Herein, we overviewed the role of GIP and GLP-1 in the pathophysiology of Type 2 Diabetes and systematically reviewed the efficacy and safety of injectable incretin-based therapy added to basal Insulin in light of the results of the SURPASS-5 trial. We identified eleven randomized clinical trials. GLP-1 Receptor agonists (GLP-1RAs) or Tirzepatide added to basal Insulin than rigorously titrated basal Insulin significantly ameliorates glucose control (Δ HbA_1c = -1%, 95% CI -1.25; -0.74, I² 94%; Δ FPG = -14.6 mg/dL, 95% CI -21.6-; -7.6, I² 90%; chance to achieve HbA_{1c <}7% = RR 2.62, 95% CI 2.10; 3.26, I² 89%), reduces body weight (Δ = -3.95 kg, 95% CI -5.1, -2.79, I² 96%) without increasing the risk of Hypoglycemia (RR = 1.01, 95% CI 0.86; 1.18, I² 7.7%). Tirzepatide provides an impressive weight loss exceeding that observed with GLP-1RAs. Injectable incretin-based therapy plus basal Insulin remains a potent and safe therapeutic approach in uncontrolled Type 2 Diabetes patients previously treated with basal Insulin alone. Tirzepatide is expected to ameliorate the management of "diabesity" in this usually difficult-to-treat cluster of patients.