Eli Lilly’s tirzepatide (Monjauro) chalks up another success with impressive Phase III results in obese and overweight patients without diabetes, showing weight reductions of up to 22.5% and minimal side effects.
Tirzepatide, Lilly’s first-in-class drug activating both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), was recently approved by the FDA for treatment of type 2 diabetes.
The SURMOUNT-1 study results, testing tirzepatide for a second indication of treatment of overweight and obesity, were presented at the at the 82nd American Diabetes Association Scientific Sessions in New Orleans, Louisiana over the weekend and simultaneously published in the New England Journal of Medicine.
The study recruited 2,539 participants who were obese (body mass index of 30 or more) or overweight (body mass index of 27 or more). The participants did not have diabetes, but did have at least one weight-related comorbidity including: high blood pressure, abnormal cholesterol levels, obstructive sleep apnea, or cardiovascular disease.
The participants were randomly divided into four groups: placebo, or 5 mg, 10 mg, or 15 mg once-weekly, subcutaneous tirzepatide for 72 weeks.
The co-primary endpoints of the study were superior percentage change in body weight from baseline with tirzepatide and that a greater percentage of participants should achieve body weight reductions of at least 5% in the treatment groups compared to the placebo group.
The primary endpoints were both met. The average weight reductions in the 5 mg, 10 mg, and 15 mg tirzepatide groups were 16%, 21.4%, and 22.5%, respectively, compared with 2.4% in the placebo group.
There were various secondary end points of the study, which were also met. These included weight reduction of 10% or more, 15% or more, and 20% or more at week 72 – these targets were met for all three doses. Another was superior change in waist circumference, which was also met. In the 5 mg, 10 mg, and 15 mg tirzepatide groups reduction in waist circumference was -14.6 cm, ‑19.4 cm and -19.9 cm, respectively, compared to -3.4 cm with placebo.
Improvements in systolic blood pressure, fasting insulin and lipid levels, and the physical function score on the 36-Item Short Form Health Survey, version 2, acute form were also observed.
There has been a quest by the medical community and big pharma to create a safe and effective drug to tackle overweight and obesity for many years, but attempts have largely ended in failure, with significant side effects killing off many potential drug candidates.
Notably, in SURMOUNT-1 side effects were mild to moderate. The most common adverse events seen at higher levels in tirzepatide treated patients versus the placebo group were gastrointestinal, such as nausea (24-31%), constipation (11-18%), vomiting (8-13%) and diarrhea (18-23%).
Overall, 25% participants in the placebo group discontinued the study compared with 14.3% (5 mg), 16.4% (10 mg), 15.1% (15 mg) in the treatment groups.
While long-term data is still lacking for tirzepatide, the results of SURMOUNT-1 are certainly promising. “Obesity should be treated like any other chronic disease—with effective and safe approaches that target underlying disease mechanisms, and these results underscore that tirzepatide may be doing just that,” said Ania Jastreboff, associate professor Yale University School of Medicine, and first author of the study describing the work.
“These results are an important step forward in potentially expanding effective therapeutic options for people with obesity. Notably, about 9 out of 10 individuals with obesity lost weight while taking tirzepatide.”
