HQ Team
November 15, 2024: Eli Lilly’s Phase III trial has yielded positive results from the SURMOUNT-1 study of tirzepatide (Zepbound and Mounjaro) for treating pre-diabetic and obese individuals.
The randomised, double-blind, placebo-controlled trial included 1,032 pre-diabetic individuals, who were either obese or suffered from cardiovascular disease, dyslipidaemia, hypertension or sleep apnea. The subjects were tested for the safety and efficacy of tirzepatide. The study was carried out for 176 weeks.
Tirzepatide, administered weekly via injection, significantly ‘decreased’ the risk of developing T2D compared to placebo over 176 weeks. At the highest 15mg dose, participants showed sustained average weight loss of 22.9% during the three-year treatment. A 94% decrease was also observed in the T2D progression risk versus placebo over three years.
Tirzepatide
Tirzepatide, developed by Eli Lilly, is designed to combat obesity and type 2 diabetes mellitus through its unique dual agonist properties that target the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors. Approved by the U.S. Food and Drug Administration (FDA) in May 2022 for type 2 diabetes and subsequently for chronic weight management in November 2023, tirzepatide has emerged as a pivotal treatment option amid a growing obesity epidemic that affects nearly one billion people globally.
Its significance lies not only in its clinical efficacy but also in its potential to improve health-related quality of life for patients battling these interconnected health issues. The drug’s mechanism of action involves enhancing insulin secretion while promoting satiety and reducing food intake.
Eli Lilly’s extensive clinical trials, particularly the SURPASS and SURMOUNT programs, have demonstrated that tirzepatide significantly improves glycemic control and promotes substantial weight loss compared to traditional treatments, including insulin and other GLP-1 receptor agonists.
Notably, the trials indicated that participants experienced average weight losses of up to 22.9% over three years, as well as enhanced treatment satisfaction and quality of life metrics.
Overview of trials
Eli Lilly has conducted multiple clinical trials to assess the efficacy and safety of tirzepatide. The drug was evaluated in a comprehensive set of studies, with a total of 7,769 participants across nine trials, of which 5,415 received tirzepatide. These trials were conducted globally, involving sites in 24 countries, including Argentina, Brazil, China, and the United States.
The Phase III SUMMIT trial focused on the effects of tirzepatide in adults with heart failure with preserved ejection fraction (HFpEF) and obesity. This multi-center, randomized, double-blind, placebo-controlled trial enrolled 731 participants. Results indicated a statistically significant reduction in adverse heart failure outcomes, including hospitalization and cardiovascular death, by 38% compared to the placebo group.
The trial also demonstrated improvements in patients’ heart failure symptoms and overall physical limitations, further supporting tirzepatide’s efficacy.
In June 2024, results from the Phase III SURMOUNT-OSA trial were published, revealing that tirzepatide significantly improved various health metrics in patients with moderate-to-severe obstructive sleep apnea (OSA) and obesity. Participants in this trial reported enhanced sleep-related outcomes, reduced body weight, and improved cardiovascular markers such as systolic blood pressure and high-sensitivity C-reactive protein concentrations.
Additional trials
Beyond these key trials, tirzepatide has been evaluated in five other major studies that compared its effects against other antidiabetic medications. These studies measured HbA1c levels over treatment durations ranging from 40 weeks to 104 weeks. Notably, the findings showed that tirzepatide led to greater reductions in HbA1c compared to its counterparts.
The combination of results from these trials has played a critical role in the FDA’s approval of tirzepatide as a treatment for type 2 diabetes and obesity, confirming its efficacy and safety profile.
In the UK, the Medicines and Healthcare products Regulatory Agency (MHRA) also authorized tirzepatide for weight management on the same day as the FDA’s announcement, further establishing its international acceptance as a valuable treatment option
Side effects and safety
However, while tirzepatide showcases considerable benefits, it is not without risks; common side effects include gastrointestinal issues such as nausea and diarrhea, with higher dosages leading to increased incidence rates. The incidence of these side effects increased with higher dosages, with a discontinuation rate of 25% among those taking the 15 mg dose, compared to 5.1% for the 5 mg dose.
Furthermore, the FDA has identified potential safety issues, such as the risk of intestinal blockage, associated with GLP-1 receptor agonists, including tirzepatide. However, inclusion of these risks does not imply direct causation, prompting healthcare providers to exercise caution regarding drug interactions and patient health
Impact
In addition to clinical outcomes, the economic implications of tirzepatide are noteworthy. A recent economic analysis indicated that tirzepatide may offer a more cost-effective treatment for patients with T2D compared to semaglutide, particularly when considering long-term health outcomes and quality-adjusted life years.
While tirzepatide has higher upfront costs, its associated clinical benefits can lead to significant savings in long-term healthcare expenses, thus providing value to both patients and the healthcare system at large.
Future research directions
Ongoing research into tirzepatide highlights several future directions for the treatment of obesity and diabetes. Future research may also investigate tirzepatide’s impact on
combination therapies, which may improve outcomes for individuals with complex health profiles.
In-depth mechanistic studies will help clarify how tirzepatide exerts its effects on appetite regulation, glucose metabolism, and fat loss. Understanding these mechanisms can inform the development of personalized treatment approaches, optimizing tirzepatide’s use.
