Tirzepatide vs. semaglutide: Study compares cost and health outcomes in obesity

In a recent study published in the Journal of Medical Economics, a group of researchers evaluated the cost-effectiveness of tirzepatide compared with semaglutide for adults with obesity or overweight in the United States (U.S.) using a lifetime simulation model informed by the SURMOUNT-5 head-to-head trial population without type 2 diabetes (T2D).

Obesity Costs and Long-Term Treatment Value

More than 70% of adults in the U.S. are overweight or have obesity, a condition linked to serious health risks such as T2D, cardiovascular disease (CVD), and obstructive sleep apnea (OSA). These health risks reduce quality of life and also create a significant financial burden for both the individual and the healthcare system as a whole.

Fortunately, new medications like tirzepatide and semaglutide have changed the landscape of weight management, offering substantial clinical benefits; however, these medications come at a high cost, raising the question of whether that investment is worthwhile.

Therefore, an understanding of the long-term economic value of these medications is necessary for patients, providers, and policymakers, and additional studies are needed to assess their lifetime cost-effectiveness.

SURMOUNT-5 Cost-Effectiveness Model Design

A patient-level simulation model was developed to compare tirzepatide and semaglutide using data from the SURMOUNT-5 Phase 3 clinical trial. The simulated population consisted of adults with obesity or overweight, defined as a body mass index (BMI) of ≥30 kg/m² or≥27 kg/m² with at least one obesity-related complication. Age, sex, BMI, glycated hemoglobin (HbA1c), systolic blood pressure (SBP), and lipid levels were derived from trial data.

The model followed patients over a lifetime horizon to reflect the chronic nature of obesity. Clinical outcomes were estimated by changes in weight, HbA1c, cholesterol, and SBP. These factors influenced the modeled risk of developing complications such as T2D, CVD, metabolic dysfunction-associated steatotic liver disease (MASLD), and OSA.

Costs were analyzed from a U.S. societal perspective, including direct healthcare costs and indirect costs, such as lost productivity from absenteeism and presenteeism. Quality-adjusted life years (QALYs), which measure both the quantity and quality of life, were used to measure health outcomes.

Incremental cost-effectiveness ratios (ICERs) and incremental net health benefits (iNHBs) were calculated to compare interventions. Sensitivity and scenario analyses were conducted to assess the robustness of the findings under different assumptions.

The base-case analysis used publicly available U.S. list prices, and additional scenarios tested publicly available net prices.

Modeled Clinical and Economic Benefits of Tirzepatide

The analysis showed that tirzepatide provided both better health outcomes and lower overall costs compared to semaglutide. Over a lifetime, patients treated with tirzepatide were projected to incur costs that were $41,688 lower per patient, while gaining an additional 0.506 QALYs compared with patients receiving semaglutide, thus indicating both longevity and improved quality of life in the model. The iNHB was also positive for tirzepatide (0.784), which further supports its greater value in this analysis.

From a clinical perspective, tirzepatide was projected to reduce the risk of major obesity-related complications. For every 1,000 patients treated, 70 fewer cases of T2D and 10 fewer cases of CVD were modeled compared with semaglutide. These two factors, when combined, could have a significant impact on long-term outcomes. Chronic disease prevention directly affects daily functioning and reduces long-term medical expenses.

In addition, tirzepatide provided significantly greater weight loss than semaglutide, an important component of improving a person's overall metabolic health. Those using tirzepatide were much more likely to return to normal blood glucose levels at 72 weeks, with 87.5% estimated to reach normoglycemia, compared with 76.88% for those receiving semaglutide.

With respect to sleep quality, tirzepatide was also projected to reduce the incidence of OSA. Patients treated with semaglutide were estimated to spend 3.07 more years of their lives living with moderate or more severe OSA than did those receiving tirzepatide. As OSA is often associated with fatigue, reduced productivity, and increased likelihood of accidents, this difference may be important for both quality of life and societal costs.

Economic benefits extended beyond healthcare costs, as tirzepatide was associated with fewer lost workdays due to illness, reducing both absenteeism and presenteeism. On average, patients treated with tirzepatide were projected to experience five fewer days of reduced productivity per year, highlighting broader societal advantages.

Importantly, these findings remained consistent across multiple sensitivity and scenario analyses. Even when assumptions about costs, treatment persistence, and patient subgroups varied, tirzepatide remained either cost-saving or highly cost-effective in the model.

Implications for Obesity Treatment Policy

Tirzepatide appears to be a cost-effective option with favorable modeled clinical outcomes compared to semaglutide for managing obesity and overweight in the U.S. In this simulation, tirzepatide was associated with greater weight loss, a lower modeled risk of developing chronic diseases such as T2D and CVD, and lower projected costs than semaglutide.

As such, tirzepatide may offer significant potential value for patients, payers, and society, and the findings highlight the importance of considering long-term value rather than upfront drug costs alone. 

As obesity continues to place a major burden on health systems, medications that can improve health outcomes while simultaneously decreasing the cost of healthcare may influence future healthcare policy and population health.