Adults ≥ 18 years of age with a body mass index (BMI) ≥ 30 kg/m2 or a BMI ≥ 27 with at least one weight-related complication (hypertension, dyslipidemia, obstructive sleep apnea or cardiovascular disease) and who reported one or more unsuccessful dietary effort to lose weight.
Those with diabetes, a change in body weight ≥ 5 kg within 90 days before screening, previous or planned surgical treatment for obesity and treatment with a medication that promotes weight loss within 90 days before screening were excluded.
Tirzepatide 5 mg (n = 630), 10 mg (n = 636), or 15 mg (n = 630) subcutaneously once weekly for 72 weeks as an adjunct to lifestyle interventions (total n = 1,896).
Placebo subcutaneously once weekly for 72 weeks as an adjunct to lifestyle interventions (n = 643).
Coprimary outcomes: percentage change in weight from baseline to week 72 and a weight reduction of 5% or more at 72 weeks.
Key secondary endpoints included: weight reduction of 10%, 15% or 20% or more at week 72; the change in weight from baseline to week 20; and the change in waist circumference, systolic blood pressure, fasting insulin and lipid levels, and the physical function score on the 36-Item Short Form Health Survey (SF-36) version 2 from baseline to week 72.
There was a four-week safety follow-up period after the 72-week treatment phase.
For adult patients with a BMI ≥ 30 or a BMI ≥ 27 and at least one weight-related complication, subcutaneous tirzepatide (5 mg, 10 mg or 15 mg) as an adjunct to lifestyle modifications yields statistically significant and substantial weight reductions when compared with placebo (mean reduction of 11.9%, 16.4% and 17.8%, respectively) while not causing a substantial increase in serious adverse events (ARD of −0.5%, 0.1% and −1.7% when compared to placebo, respectively). While the study may have some risk of bias due to lack of blinding in certain individuals involved in the trial and due to the risk for co-intervention, the study demonstrated good validity overall with robust absolute differences with efficacy data and sufficient duration of study (72 weeks) to detect differences in the outcomes. This study expands the usage of tirzepatide beyond lowering A1C in Type 2 diabetes. However, there is still lack of data in patients with Type 1 diabetes mellitus, and tirzepatide has not been studied in those with history of pancreatitis as with other GLP-1 agonists. In addition, it also carries the boxed warning of risk of thyroid C-cell tumor. Longer studies are needed to evaluate the sustainability of tirzepatide’s weight loss effect for extended duration. Health care professionals should evaluate the applicability and risk in order to ensure proper use of this medication given the high burden of its prescription cost (AWP = $1,227.65/four weeks).7
Tirzepatide is a prescription medication that is injected under the skin (subcutaneously) once weekly. This medication was originally indicated to treat patients with Type 2 diabetes along with diet and exercise by increasing insulin (a hormone that controls the level of sugar in blood) when needed and decreasing glucagon (a hormone that produces sugar). It also lets food pass through the stomach slower, meaning sugar from food will take longer to get into the blood. The results of this study showed that tirzepatide along with diet and exercise can help people without diabetes who suffer from obesity achieve up to a 20% reduction in weight compared with diet and exercise alone. While this article did not study patients with diabetes, previous trials in patients with Type 2 diabetes showed similar weight loss benefit.2–6 This medication may cause stomach upset including nausea, vomiting, diarrhea and constipation. This medication cannot be used if a patient had inflammation of pancreas previously or have a personal or family history of certain thyroid tumors. Overall, tirzepatide can be an important tool in managing weight in people without diabetes along with diet and exercise, if previous weight loss efforts have failed.
About the Editor
Cynthia Jackevicius, BScPhm, PharmD, MSc, BCPS, BCCP, FCSHP, FAHA, FCCP, FCCS, FACC, a professor of pharmacy practice at Western University of Health Sciences, is the evidence-based practice section editor. Dr. Jackevicius teaches evidence-based practice skills to health care professionals. She advocates for the adoption of an evidence-based practice, incorporating the best available evidence, patients’ values and preferences, and clinicians’ expertise into clinical decision-making. She has no conflicts of interest to report.
