Tirzepatide Reduces Risk of Progression to Type 2 Diabetes for Patients with Obesity, Overweight

For adults receiving the 15 mg dose, tirzepatide sustained weight loss with an average reduction of 22.9% in body weight compared with 2.1% for the placebo.

Weekly tirzepatide (Zepbound, Mounjaro; Eli Lilly and Company) injections significantly reduced risk of progression to type 2 diabetes (T2D) by approximately 94% for those with prediabetes and obesity or overweight when compared with a placebo, according to results from the SURMOUNT-1 (NCT04184622) study. The SURMOUNT-1 trial lasted 176 weeks, evaluating the efficacy and safety of the drug as a once weekly injection for long-term weight management and reduction in disease progression to diabetes.¹

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"Obesity is a chronic disease that puts nearly 900 million adults worldwide at an increased risk of other complications such as type 2 diabetes," Jeff Emmick, MD, PhD, senior vice president of product development at Lilly, said in a news release. "Tirzepatide reduced the risk of developing type 2 diabetes by 94% and resulted in sustained weight loss over the 3-year treatment period. These data reinforce the potential clinical benefits of long-term therapy for people living with obesity and pre-diabetes."¹

For adults receiving the 15 mg dose, tirzepatide sustained weight loss with an average reduction of 22.9% in body weight compared with 2.1% for the placebo at the end of the treatment period.¹

In the phase 3 multicenter, double-blind trial, investigators included adults 18 years and older with a body mass index (BMI) of 20 or more, or a BMI of 27 or more and at least 1 weight-related comorbidity—hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease—from 119 sites in 9 countries. Individuals include also had 1 or more unsuccessful dietary effort to lose weight and were excluded if they had diabetes, previous or planned surgical treatment for obesity, and treatment with a medication that promoted weight loss 90 days prior to screening.²

After a 2-week screening period, individuals were assigned treatment on a 1:1:1:1 ratio of tirzepatide at 5 mg, 10 mg, 15 mg, or the placebo, which were administered subcutaneously once weekly for 72 weeks along with lifestyle intervention, including lifestyle counseling that helped the patient adhere to balance meals with a deficit of 500 calories per day and at least 150 minutes of physical activity per week, according to the study authors.²

About The Trial

Trial Name: A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight (SURMOUNT-1)

ClinicalTrials.gov ID: NCT04184622

Sponsor: Eli Lilly and Company

Completion Date: July 2024

The trial was conducted from December 2019 to April 2022, with a total of 2539 individuals, of whom 86% completed the primary trial treatment period and 81.6% adhered to the treatment. Discontinuation due to adverse events were 4.3%, 7.1%, 6.2%, and 2.6% with the 5 mg, 10 mg, 15 mg, and the placebo, respectively.²

For the follow up, tirzepatide (10 mg and 15 mg) lead to statistically significant weight reductions from baseline to week 176 at 19.9% and 22.9%, respectively, compared to the placebo at 2.1%. The 5 mg dose led to a reduction of 15.4%. Investigators reported that the overall safety and tolerability of tirzepatide over the 193-week period was consistent with the results published at 72 weeks.¹

At 72 weeks, 78.9% to 81.8% of individuals treated with tirzepatide reported at least 1 adverse event (AE) compared with 72% of those in the placebo group. The most frequently reported AEs were gastrointestinal, such as nausea, diarrhea, and constipation. Serious AEs were reported by 6.3% of patients overall, with similar percentages between the study drug and the placebo groups. Approximately 21% were attributed to COVID-19 (all in the treatment groups), and 11 deaths (7 in the tirzepatide group; 4 in the placebo group) were reported.²

REFERENCES

1. Tirzepatide reduced the risk of developing type 2 diabetes by 94% in adults with pre-diabetes and obesity or overweight. News release. Eli Lilly and Company. August 20, 2024. August 21, 2024. https://investor.lilly.com/news-releases/news-release-details/tirzepatide-reduced-risk-developing-type-2-diabetes-94-adults

2. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205-216. doi:10.1056/NEJMoa2206038