Who are the Best Candidate Patients with Diabetes for Tirzepatide?

Background: Tirzepatide is a dual receptor agonist of the 2 incretin hormones: Glucose-Dependent Insulinotropic Polypeptide (GIP) and Glucagon- Like Peptide-1 (GLP-1) which is was recently approved for treatment of type 2 diabetes. Objective: To define the most appropriate patients that may benefit from tirzepatide. Methods: Pubmed search until August 10, 2022. Search terms were GLP- 1, GIP, tirzepatide, efficacy, safety, obesity. Clinical trials and pertinent animal studies and reviews were included. Results: Tirzepatide was more effective in lowering hemoglobin A1c (HbA1c) levels and body weight than submaximal doses of semaglutide (1.0 mg once-weekly), dulaglutide (1.5 mg once-weekly), insulin degludec (mean daily dose 48.8 U) and insulin glargine (mean daily dose 43.5 U). In patients with type 2 diabetes and Non-Alcoholic Fatty Liver Disease (NAFLD), tirzepatide significantly decreased Liver Fat Content (LVC). Safety profile of tirzepatide was generally similar to that of GLP-1 agonists, but frequency of Gastrointestinal (GI) adverse effects are slightly higher with tirzepatide. Incidence of severe hypoglycemia (blood glucose < 54 mg/dl) is also slightly higher with tirzepatide than semaglutide and dulaglutide, but much lower than insulin degludec and glargine. Drug discontinuation rates due to adverse effects were higher with tirzepatide compared with semaglutide, dulaglutide, and insulin. Conclusions: Tirzepatide may be most appropriate for patients with type 2 diabetes who are obese, as alternative to GLP-1 agonists or basal insulin, and in patients with NAFLD.