Tirzepatide, the dual GLP-1 and GIP agonist showed ground breaking weight loss and HbA1c reduction in overweight or obese people with type 2 diabetes: Result of the SURMOUNT-2 trial

Abstract

Tirzepatide, a dual GLP-1, GIP uni-molecular agonist had previously shown a significant ~22% weight loss in the SURMOUNT-1 pivotol trial and received FDA approval in 2022. The percentage weight loss observed in that study was indeed the largest weight loss seen in an anti-obesity, weight loss trial to date. Previous studies have also shown that the efficacy of anti-obesity drugs to induce weight loss in people with type 2 diabetes is typically less when compared to people without type 2 diabetes. The largest weight loss seen in overweight/obese people with type 2 diabetes was previously observed with Semaglutide 2.4 mg (Wegovy) in the STEP-2 trial. Previous large-scale trials with tirzepatide in people with type 2 diabetes in the SURPASS programme did not focus patients with type 2 diabetes who are also overweight or obese. Against this background, the SURMOUNT-2 pivotal trial investigated the efficacy of tirzepatide in people with type 2 diabetes who are also overweight/obese. The result of this important trial was presented at the American Diabetes Association (ADA2023) meeting. The trial reported that weekly tirzepatide injections in adults with type 2 diabetes and overweight or obesity safely led to 12.8%–14.7% in-trial weight loss for 10 and 15 mg of tirzepatide respectively after 72 weeks—a finding that will likely lead to US Food and Drug Administration (FDA) approval of a new indication for weight loss for tirzepatide. The observed weight loss of approximately 15% from baseline was the first to be seen with any anti-obesity therapy in people with type 2 diabetes. Amazingly, up to 34% of patients achieved >20% weight reduction. As in the SURPASS trial programme, the greatest rate of weight loss was seen in the first 24 weeks of treatment. This magnitude of weight loss throughout the study was associated with approximately 2.1% absolute HbA1c reduction. In addition to weight and HbA1c reduction, all key secondary end-points that included systolic blood pressure, lipid parameters, fasting glucose and waist circumference, were all met. While direct head-to-head comparison between studies was not possible, these findings easily placed Tirzepatide, marketed as Mounjaro in a favourable position relative to a 2.4-mg weekly subcutaneous injection with the GLP-1 agonist semaglutide (Wegovy) for weight loss. This new findings therefore support the assertion that tirzepatide is currently the most effective agent currently on the market to help achieve the two co-primary goals for patients with type 2 diabetes—weight loss and glycaemic control—while also having favourable effects on cardiovascular risk factors. The study is published in the Lancet.^[1]