Contributor: Jalen Love, PharmD Candidate 2027, PCOM Georgia School of Pharmacy
John is a 57-year-old man who was diagnosed with type 2 diabetes mellitus two years ago and has been actively managing his blood glucose with diet, exercise, and semaglutide. John was also diagnosed with coronary artery disease (CAD) five years ago, as well as chronic sleep apnea, and is clinically considered obese with a BMI of 35.7. At John’s most recent visit, his provider discussed with him a new option: tirzepatide, a once-weekly injection that works on both the GIP and GLP-1 pathways. Intrigued by the possibility of improved glycemic control and additional weight loss, John asked, “Is this only for diabetes and weight loss—or can it help me in other ways too?”
In 2022, tirzepatide, under the brand name Mounjaro, was approved by the FDA as a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist for the treatment of type 2 diabetes. It gained further attention when clinical trials demonstrated significant weight reduction, leading to its 2023 approval under the name Zepboundfor chronic weight management in patients with obesity or overweight and associated comorbidities.
However, the scope of tirzepatide is rapidly expanding beyond glycemic control and weight loss. Current clinical trials and emerging evidence suggest promising roles in addressing a broad spectrum of metabolic and cardiovascular conditions.
Expanding Cardiometabolic Care
- Heart Failure with Preserved Ejection Fraction (HFpEF):
HfpEF is a common comorbidity among individuals with obesity and type 2 diabetes. The SURMOUNT and SURPASS-HF trials explore tirzepatide’s functional capacity and overall impact on quality of life in patients with HFpEF. Early data suggest improvements in symptoms and exercise tolerance. In the mentioned study, through a randomized(double-masked) trial, ~730 patients with class II-IV heart failure with EF greater than or equal to 50% with a concurrent BMI of greater than or equal to 30 kg/m2 were chosen to be given a placebo or tirzepatide. Tests to determine clinical variability included a 6-minute walk distance, ED-5D-5L health state index, and Patient Global Impression of Severity Overall Health score. Compared to placebo, tirzepatide produced a consistent improvement in worsening heart failure events and composites of death; they also improved Patient Global Impressional scores and required fewer heart failure medications after the study’s conclusion.
- Atherosclerotic Cardiovascular Disease (ASCVD) Risk Reduction:
Similar to GLP-1 receptor agonists, tirzepatide may reduce major adverse cardiovascular events (MACE) in individuals at high risk. The ongoing SURPASS-CVOT trial states its primary outcome is determining the percentage of participants who achieve more than 5% body weight reduction within 72 weeks. Secondary outcomes include the following: with doses of tirzepatide 10 mg or 15 mg, they determined the rate of change in BMI, fasting glucose, fasting insulin, and body weight reductions of 5,15 and 20%.
The study consists of two phases: the primary phase and the extension phase; the main phase of the study will last a total of 72 weeks, and the extension will include patients who would continue the study beyond that point who were pre-diabetic to assess the progression to type 2 diabetes. This study concluded that with a dose of 15 mg of tirzepatide, patients achieved 20% of weight reduction. Among the extension phase group(with prediabetes), there was a reduction of progression to type 2 diabetes above 90%.
Given John’s personal and family history of heart disease, his diagnosis of CAD, and chronic sleep apnea, his provider emphasized the potential benefits of tirzepatide beyond blood sugar control. It can potentially reduce cardiovascular risk and support weight loss. After discussion, John and his provider decided to initiate therapy with a comprehensive plan to monitor his glycemic status, cardiovascular markers, and sleep quality.
Three months later, John returned with encouraging updates: improved energy levels, notable weight loss, and normalization of liver function tests—demonstrating that the benefits of tirzepatide may extend well beyond diabetes management.
References
- “Drug Approvals and Databases.” U.S. Food and Drug Administration, U.S. Department of Health and Human Services, www.fda.gov/drugs/drug-approvals-and-databases. Accessed 8 June 2025.
- “Standards of Care in Diabetes—2025.” Diabetes Care, vol. 48, suppl. 1, 2025, pp. S1–S200, doi:10.2337/dc25-S001.
- Jastreboff, Ania M., et al. “Tirzepatide Once Weekly for the Treatment of Obesity.” The New England Journal of Medicine, vol. 387, no. 3, 2022, pp. 205–216, doi:10.1056/NEJMoa2206038.
- Sattar, Naveed, et al. “Dual GIP/GLP-1 Receptor Agonists in Cardiometabolic Disease.” The Lancet Diabetes & Endocrinology, vol. 11, no. 1, 2023, pp. 13–26, doi:10.1016/S2213-8587(22)00315-5.
- “Tirzepatide – Clinical Trials.” ClinicalTrials.gov, U.S. National Library of Medicine, clinicaltrials.gov/ct2/results?cond=&term=tirzepatide&cntry=&state=&city=&dist=. Accessed 8 June 2025.
- Zile, Michael R., et al. “Effects of Tirzepatide on the Clinical Trajectory of Patients with Heart Failure, Preserved Ejection Fraction, and Obesity.” Circulation, vol. 151, no. 10, 11 Mar. 2025, pp. 656–668. PubMed, doi:10.1161/CIRCULATIONAHA.124.072679.
- Dominguez H., et al. “SURPASS‑CVOT Design and Baseline Characteristics: A Cardiovascular Outcomes Trial of Tirzepatide in Type 2 Diabetes.” American Heart Journal, vol. 268, 2023, p. 1, doi:10.1016/j.ahj.2023.09.007. PubMed, PMID 37758044.
- Bastin, Marie, and Fabrizio Andreelli. “Dual GIP–GLP1-Receptor Agonists In The Treatment Of Type 2 Diabetes: A Short Review On Emerging Data And Therapeutic Potential.” Diabetes, Metabolic Syndrome and Obesity, vol. 12, no. , 2019, pp. 1973-1985.
