Eli Lilly and Company's provided results that Adults with type 2 diabetes with increased cardiovascular risk experienced superior A1C and body weight reductions from baseline across all three doses of tirzepatide compared to titrated insulin glargine. At 52 weeks, the highest dose of tirzepatide led to an A1C reduction of 2.58 % and reduced body weight by 11.7 kg compared to results for those treated with insulin glargine. SURPASS-4 is the largest and longest clinical trial completed to date of the phase 3 program studying tirzepatide as a potential treatment for type 2 diabetes. The primary endpoint was measured at 52 weeks, with participants continuing treatment up to 104 weeks or until study completion. The completion of the study was triggered by the accrual of major adverse cardiovascular events to assess CV risk. In newly published data from the treatment period after 52 weeks, participants taking tirzepatide maintained A1C and weight control for up to two years. The overall safety profile of tirzepatide, assessed over the full study period, was consistent with the safety results measured at 52 weeks, with no new findings up to 104 weeks. Gastrointestinal side effects were the most commonly reported adverse events, usually occurring during the escalation period and then decreasing over time. Tirzepatide is a novel investigational once-weekly dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist that integrates the actions of both incretins into a single molecule, representing a new class of medicines being studied for the treatment of type 2 diabetes. SURPASS-4 was an open-label global trial comparing the safety and efficacy of three tirzepatide doses to titrated insulin glargine in 2,002 adults with type 2 diabetes with increased CV risk who were treated with between one and three oral antihyperglycemic medicines. Of the total participants randomized, 1,819 completed the primary 52-week visit and 1,706 completed the study on treatment. The median study duration was 85 weeks and 202 participants completed two years. Study participants had a mean duration of diabetes of 11.8 years, a baseline A1C of 8.52% and a baseline weight of 90.3 kg. More than 85% of participants had a history of cardiovascular events. In the insulin glargine arm, the insulin dose was titrated following a treat-to-target algorithm with the goal of fasting blood glucose below 100 mg/dL. The starting dose of insulin glargine was 10 units per day, and the mean dose of insulin glargine at 52 weeks was 43.5 units per day. Tirzepatide is a once-weekly dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist that integrates the actions of both incretins into a single novel molecule. GIP is a hormone that may complement the effects of GLP-1. In preclinical models, GIP has been shown to decrease food intake and increase energy expenditure therefore resulting in weight reductions, and when combined with a GLP-1 receptor agonist, may result in greater effects on glucose and body weight. Tirzepatide is in phase 3 development for blood glucose management in adults with type 2 diabetes, for chronic weight management and heart failure with preserved ejection fraction. It is also being studied as a potential treatment for non-alcoholic steatohepatitis.