Tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, and semaglutide, a GLP-1 receptor agonist, are approved therapies for type 2 diabetes (T2D). Clinical trials have shown greater hemoglobin A1c and weight reductions with tirzepatide versus comparators, and prior modeling suggested potential economic advantages. The objective of this retrospective real-world study was to compare treatment patterns, A1c and weight outcomes, and type 2 diabetes–related pharmacy (T2D-Rx) cost per patient achieving treatment targets among adults initiating tirzepatide or semaglutide in the United States, with analyses stratified by prior GLP-1 RA exposure.
The analysis used claims and laboratory data from the Healthcare Integrated Research Database. Adults with T2D initiating tirzepatide (Mounjaro only) or semaglutide (Ozempic only) between May 2022 and May 2023 were identified. The study followed patients for 12 months after initiation to assess treatment patterns, clinical outcomes, and pharmacy costs.
Tirzepatide and semaglutide initiators were propensity score matched to balance baseline characteristics. Patients were classified as GLP-1 RA–naive or GLP-1 RA–non-naive based on any GLP-1 RA exposure during the 6 months before index drug initiation. After matching, the analysis included 10,702 naive pairs and 5,577 non-naive pairs in each treatment group.
Prespecified outcomes over 12 months included adherence, defined as proportion of days covered (PDC) ≥0.80, and persistence, defined as no treatment gap of 45 days or more. Clinical effectiveness outcomes were attainment of A1c thresholds (<8%, <7%, ≤6.5%, <5.7%) and weight-loss thresholds (≥5%, ≥10%, ≥15%).
Economic evaluation used a cost-per-responder approach: T2D-Rx cost per responder was calculated as the mean T2D-related pharmacy cost divided by the proportion of patients achieving each treatment target. Comparisons between cohorts used chi-square and t-tests as appropriate.
Across both GLP-1 RA–naive and non-naive strata, tirzepatide initiators demonstrated higher adherence and persistence than semaglutide initiators. Specifically, adherence (PDC ≥0.80) among tirzepatide versus semaglutide initiators was 60% versus 45% in the naive cohort and 66% versus 48% in the non-naive cohort. Persistence (no ≥45-day gap) favored tirzepatide as well: 62% versus 47% in naive patients and 68% versus 49% in non-naive patients.
A greater proportion of tirzepatide users achieved all reported A1c and weight outcomes compared with semaglutide users. For the most stringent endpoints, differences were notable. A1c <5.7% was achieved by 30% of tirzepatide versus 18% of semaglutide initiators in the naive cohort, and by 17% versus 6% in the non-naive cohort. For weight loss ≥15%, tirzepatide achieved rates of 23% versus 10% for semaglutide in naive patients, and 17% versus 5% in non-naive patients. For less stringent A1c goals, the study reports similar cost-per-responder findings between treatments (see economic results), while absolute achievement rates remained higher with tirzepatide across reported thresholds.
The study's cost-per-responder analyses indicate that T2D-Rx cost per responder was lower for tirzepatide for the most stringent clinical endpoints. Examples provided in the study include:
For many weight-loss thresholds, tirzepatide also showed lower T2D-Rx cost per responder. By contrast, for less stringent A1c goals the reported cost per responder was similar between the two treatments.
In this real-world, propensity score–matched analysis of US adults with T2D, initiating tirzepatide was associated with better adherence and persistence, higher proportions achieving both A1c and weight targets, and lower T2D-Rx cost per responder for the most stringent endpoints compared with initiating semaglutide, in both GLP-1 RA–naive and non-naive patients. The authors interpret these findings as supporting the clinical and economic value of tirzepatide for achieving meaningful treatment outcomes in routine practice.
Conflict of interest disclosures indicate that several authors are employees and stockholders of Eli Lilly and Company, and that Carelon Research received funding from Eli Lilly to conduct the study and to assist with manuscript writing. Sponsorship for the study was provided by Eli Lilly and Company. These disclosures are reported in the source article.