Eli Lilly and Company has announced positive topline results from the SURMOUNT-1 three-year study (176-week treatment period) evaluating the efficacy and safety of tirzepatide (Mounjaro) once weekly for long-term weight management, alongside a reduced-calorie diet and increased physical activity, and delay in progression to diabetes in adults with pre-diabetes and obesity or overweight.
Weekly tirzepatide injections (5mg, 10mg, 15mg) significantly reduced the risk of progression to type 2 diabetes by 94% among adults with pre-diabetes and obesity or overweight compared to placebo. Additionally, treatment with tirzepatide resulted in sustained weight loss through the treatment period, with adults on the 15mg dose experiencing a 22.9% average decrease in body weight compared to 2.1% for placebo in adults with pre-diabetes and obesity or overweight at the end of the treatment period.
SURMOUNT-1 studied adults with obesity or overweight without diabetes and included a total of 2539 patients. 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 (for a total treatment period of 176 weeks), followed by a 17-week off treatment period, 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.
All participants treated with tirzepatide started the study at a dose of 2.5mg once-weekly for four weeks. Then the dose of tirzepatide was increased by 2.5mg every four weeks until they reached their assigned dose, either 5mg, 10mg, or 15mg subcutaneously once-weekly during a 20-week period followed by the maintenance period.
“Obesity is a chronic disease that comes with an increased risk of other complications such as type 2 diabetes, and 26% of adults in England are living with obesity” said Emily Pegg, Medical Director for Lilly Northern Europe. “Tirzepatide reduced the risk of developing type 2 diabetes by 94% and resulted in sustained weight loss over the three-year treatment period. This data provides further evidence for the potential clinical benefits of long-term therapy for people living with obesity and pre-diabetes.”
In a key secondary endpoint, tirzepatide (10mg and 15mg) led to statistically significant weight reduction compared to placebo in adults with pre-diabetes and obesity or overweight from baseline to week 176 (p<0.001). For the efficacy estimand, adults taking tirzepatide achieved average weight reductions of 15.4% (5mg), 19.9% (10mg) and 22.9% (15mg) compared to placebo (2.1%) at week 176. For the treatment-regimen estimandiv, adults taking tirzepatide achieved average weight reductions of 12.3% (5mg), 18.7% (10mg) and 19.7% (15mg) compared to placebo (1.3%) at week 176.
In an additional key secondary endpoint, pooled doses of tirzepatide (5, 10 and 15mg) led to a significant reduction in the risk of progression to type 2 diabetes in adults with pre-diabetes and obesity or overweight from baseline to week 176 (p<0.0001). For the efficacy estimand, pooled doses of tirzepatide demonstrated a 94% reduction in risk of progression to type 2 diabetes compared to placebo up to week 176. For the treatment-regimen estimand, pooled doses of tirzepatide resulted in a 93% reduction in risk of progression to type 2 diabetes compared to placebo up to week 176.
The overall safety and tolerability profile of tirzepatide over the 193-week study was consistent with the previously published primary results at 72 weeks in SURMOUNT-1 and other tirzepatide clinical studies conducted for weight management. The most frequently reported adverse events were typically gastrointestinal-related and generally mild to moderate in severity. The most common gastrointestinal-related adverse events for patients treated with tirzepatide were diarrhoea, nausea, constipation and vomiting.
Tirzepatide, a GIP and GLP-1 receptor agonist, works by activating the two hormone receptors. GLP-1 is a regulator of appetite and caloric intake. Nonclinical studies suggest the addition of GIP may further contribute to the regulation of food intake. Tirzepatide decreases calorie intake, and the effects are likely mediated by affecting appetite. In addition, tirzepatide stimulates insulin secretion in a glucose-dependent manner. Tirzepatide increases insulin sensitivity in patients with type 2 diabetes mellitus and these effects can lead to a reduction of blood glucose.
These topline results provide evidence for reduced risk of progression to type 2 diabetes and long-term maintenance of weight loss with tirzepatide in adults with pre-diabetes and obesity or overweight. Detailed results will be submitted to a peer-reviewed journal and presented at Obesity Week 2024, which will take place 3rd – 6th November.
SURMOUNT-1 (NCT04184622) 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 have obesity, or overweight with at least one of the following comorbidities: hypertension, dyslipidaemia, obstructive sleep apnoea (OSA) 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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