Results from the Phase 3 SURMOUNT-1 three-year study (176-week treatment period), the longest completed study to date of tirzepatide, have revealed that weekly tirzepatide (Zepbound and Mounjaro) injections (pooled 5mg, 10mg, 15mg doses) significantly reduced the risk of progression to type 2 diabetes in adults with pre-diabetes and obesity or overweight, compared with placebo, over 176 weeks.
In addition, tirzepatide demonstrated sustained average weight loss of 22.9% (15mg dose) through the three-year treatment period for the efficacy estimand. These findings were published in the paper, ‘Tirzepatide for Obesity Treatment and Diabetes Prevention’, in The New England Journal of Medicine (NEJM) and recently presented at ObesityWeek 2024.
"Individuals treated with tirzepatide lost on average up to 23% of their body weight and maintained this for over three years, while benefitting from a substantial decrease in risk of developing type 2 diabetes. In absolute terms, nearly 99% of individuals treated with tirzepatide remained diabetes-free at 176 weeks," said Dr Ania Jastreboff, director of the Yale Obesity Research Center. "These results are impressive given the degree of sustained weight reduction and decrease in risk of diabetes."
In additional endpoints, the study showed an association of tirzepatide treatment with improvements in glycaemic control, cardiometabolic risk factors (including fasting insulin, blood pressure and lipids) and health-related quality of life, which were sustained through 176 weeks.
A post hoc mediation analysis suggested that approximately half of the observed effect in delay to onset of type 2 diabetes with tirzepatide was associated with medication-induced weight reduction, with the remaining benefit potentially attributed to other effects of tirzepatide.
"In the SURMOUNT-1 three-year study of tirzepatide, an average weight reduction of up to 22.9% was accompanied by a hazard ratio of 0.06 for progression to type 2 diabetes. This translates to a risk reduction of 94% and a number needed to treat of nine to prevent one case of diabetes," said Dr Jeff Emmick, senior vice president, product development, Lilly. "These results underscore the critical role of long-term therapy with effective treatments like tirzepatide to achieve and maintain weight reduction."
The overall safety and tolerability profile of tirzepatide at 193 weeks (176 weeks followed by 17 weeks off-treatment) was consistent with the previously published results at 72 weeks for SURMOUNT-1 and other tirzepatide clinical studies conducted for weight reduction and long-term maintenance. Other than COVID-19, the most frequently reported adverse events were gastrointestinal-related and generally mild to moderate in severity. The most common gastrointestinal-related adverse events in patients treated with tirzepatide were nausea, diarrhoea and constipation.
SURMOUNT-1 was a multi-centre, randomised, double-blind, parallel, placebo-controlled trial comparing the efficacy and safety of tirzepatide 5mg, 10mg and 15mg to placebo as an adjunct to a reduced-calorie diet and increased physical activity in adults without type 2 diabetes who had obesity, or overweight with at least one of the following comorbidities: hypertension, dyslipidaemia, obstructive sleep apnoea or cardiovascular disease. The 1,032 participants who had pre-diabetes at study commencement remained enrolled in SURMOUNT-1 for an additional 104 weeks of treatment following the initial 72-week completion date to evaluate the impact on body weight and potential differences in progression to type 2 diabetes at three years of treatment with tirzepatide, compared to placebo.
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