OR03-1 Achievement of HbA1c <6.5% without weight gain and hypoglycemia in people with type 2 diabetes treated with tirzepatide across the phase 3 SURPASS program

Abstract

Abstract Introduction Tirzepatide, the novel dual GIP/GLP-1 receptor agonist for the treatment of type 2 diabetes, has been shown to reduce HbA1c and weight, with more patients achieving HbA1c ≤6.5%, compared to placebo and active comparators in the phase 3 SURPASS 1-5 studies. This analysis compared the percentage of patients treated with tirzepatide achieving a composite endpoint of HbA1c <6.5% without weight gain and hypoglycemia in these studies. Methods We compared the proportion of participants achieving the composite endpoint between the tirzepatide (5, 10, or 15 mg) and respective comparator groups while patients were on treatment and without rescue medication. Missing data was imputed based on observed data in the same treatment arm from subjects who had their efficacy measure at the endpoint visit assessed after early discontinuation of study drug. End of treatment HbA1c and weight were evaluated at week 40 (SURPASS-1, 2, 5) and week 52 (SURPASS-3, 4). Weight gain was defined as a change from baseline in weight <0.1 kg. Hypoglycemia included blood glucose level <54 mg/dL with symptoms of hypoglycemia or severe hypoglycemia. Results In SURPASS-1, 2, 3, 4, and 5 significantly more patients treated with tirzepatide achieved the composite endpoint compared to placebo or comparator (P≤0.002). As a monotherapy in SURPASS-1, significantly more patients treated with tirzepatide 5mg, 10mg, 15mg achieved the composite endpoint than placebo (75%, 78%, 83%, and 5%, respectively; all P<0.001). As add-on to metformin in SURPASS-2, significantly more patients treated with tirzepatide 5mg, 10mg, 15mg achieved the composite endpoint than semaglutide (67%, 77%, 83%, and 59%, respectively; P=0.002, P<0.001, P<0.001, respectively). When compared to basal insulin in SURPASS-3, significantly more patients treated with tirzepatide 5mg, 10mg, 15mg achieved the composite endpoint than insulin degludec (63%, 76%, 82%, and 13%, respectively; all P<0.001). When added to 1-3 oral antihyperglycemics in SURPASS-4, significantly more patients treated with tirzepatide 5mg, 10mg, 15mg achieved the composite endpoint than insulin glargine (56%, 68%, 75%, and 10%, respectively; all P<0.001). As an add-on to basal insulin in SURPASS-5, significantly more patients treated with tirzepatide 5mg, 10mg, 15mg achieved the composite endpoint than placebo (63%, 70%, 76%, and 8% respectively; all P<0.001). Conclusions Significantly more patients treated with tirzepatide achieved a composite endpoint of HbA1c <6.5% without weight gain or hypoglycemia than those treated with placebo, semaglutide, insulin degludec, or insulin glargine in the phase 3 SURPASS program. Presentation: Saturday, June 11, 2022 11:30 a.m. - 11:45 a.m.