Tirzepatide

Jastreboff AM et al. 2022. "Tirzepatide Once Weekly for the Treatment of Obesity." N Engl J Med 387(3): 205-216. [PMID: 35658024](https://pubmed.ncbi.nlm.nih.gov/35658024/)

Population: Adults with obesity or overweight without diabetes

Dose protocol: Tirzepatide 5, 10, 15 mg weekly vs placebo. 20-week step-up to maintenance

Key findings: Mean percent weight change at 72 weeks was approximately -15.0%, -19.5%, and -20.9% for 5/10/15 mg versus -3.1% placebo.

Notes: Pivotal obesity efficacy anchor and tolerability benchmark.

Rubino DM et al. 2023. "Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2)." Lancet. [PMID: 37385275](https://pubmed.ncbi.nlm.nih.gov/37385275/)

Population: Adults with obesity/overweight and type 2 diabetes

Dose protocol: Tirzepatide 10 or 15 mg weekly vs placebo for 72 weeks

Key findings: Mean weight reductions of ~13.4% (10 mg) and 15.7% (15 mg) and meaningful HbA1c gains versus placebo.

Notes: Diabetes-weight crossover evidence. Stronger applicability to comorbid obesity and glycemic populations.

Frias JP et al. 2021. "A Study of Tirzepatide vs Semaglutide Once Weekly as Add-on Therapy to Metformin in Type 2 Diabetes (SURPASS-2)." N Engl J Med 385(6): 503-515. DOI: 10.1056/NEJMoa2107519.

Population: Adults with type 2 diabetes on metformin

Dose protocol: Tirzepatide 5, 10, 15 mg vs semaglutide 1 mg weekly over 40 weeks

Key findings: Tirzepatide improved HbA1c and weight more than semaglutide 1 mg. Discontinuation for adverse effects was modestly higher with some tirzepatide doses.

Notes: Supports comparative protocol selection in diabetes programs. Open-label design affects performance bias.

SURMOUNT-1 3-year follow-up: treatment-era weight reduction and reduced diabetes progression, with partial attenuation after 17-week off-treatment follow-up. https://www.prnewswire.com/news-releases/treatment-with-tirzepatide-in-adults-with-pre-diabetes-and-obesity-or-overweight-resulted-in-sustained-weight-loss-and-nearly-99-remained-diabetes-free-at-176-weeks-302304834.html

Population: Adults with obesity and prediabetes in SURMOUNT-1

Dose protocol: 5/10/15 mg weekly over 176 weeks, plus 17-week off-treatment period

Key findings: Sustained treatment-era weight reduction, significant diabetes-risk reduction versus placebo, and partial weight/glycemic attenuation after treatment interruption.

Notes: Useful for maintenance planning. Publication-grade details should be refreshed when full peer-reviewed 176-week manuscript is available.

FDA drug-safety communication and warning-letter context for unapproved/compounded tirzepatide products, plus linked prescriber labeling references (boxed warning and contraindications). https: //www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss

Population: Approved prescribing population

Dose protocol: Prescribing and safety instructions across approved regimens

Key findings: Confirms dosing framework, MTC/MEN2 contraindications, and safety monitoring requirements in approved use.

Notes: Highest confidence source for contraindication and risk thresholds.

FDA approval communication for chronic weight management indication (Zepbound) including obesity criteria, dose-escalation framing, and indication details. https: //www.fda.gov/news-events/press-announcements/fda-approves-new-medication-chronic-weight-management

Population: Adults with obesity or overweight plus comorbidity

Dose protocol: Approved obesity pathway dosing and escalation context

Key findings: Establishes intended clinical-use context and coadministration restrictions.

Notes: Clinical protocol logic should remain aligned with current national/regional approvals.

Lilly-supported long-term (176-week) efficacy and post-treatment safety/discontinuation context with follow-up beyond 17 weeks after treatment interruption. https: //www.prnewswire.com/news-releases/treatment-with-tirzepatide-in-adults-with-pre-diabetes-and-obesity-or-overweight-resulted-in-sustained-weight-loss-and-nearly-99-remained-diabetes-free-at-176-weeks-302304834.html

Population: Trial populations across obesity and diabetes programs

Dose protocol: Multiple SURMOUNT and SURPASS dosing schedules

Key findings: Reiterates additive GI tolerance burden and protocol adherence effects on completion.

Notes: Useful as context source, not primary efficacy replacement.

Schmidt PHS, de Souza VSN, Machado LG, Rodrigues JVA, da Cruz JVR, de Souza LSN, Dos Santos BE, Hohl A, Ronsoni MF, van de Sande-Lee S. Tirzepatide on physical function in adults with overweight or obesity: A systematic review and meta-analysis. Diabetes Obes Metab. 2026;28(4):3335-3343. doi:10.1111/dom.70529. PMID:41705736.

Population: Adults with overweight or obesity from six RCTs.

Dose protocol: Meta-analysis of 6 RCTs, tirzepatide 10 or 15 mg weekly versus placebo (4,531 participants)

Key findings: Significant improvements in SF-36 physical function (MD 2.26, 95% CI 1.76 to 2.76) and IWQOL-Lite-CT physical function (MD 10.10, 95% CI 8.61 to 11.60). Both doses showed consistent benefit.

Notes: First pooled analysis of tirzepatide on physical function specifically. Substantial heterogeneity noted.

Monzo L, Savarese G, Duarte K, Baudry G, Petrie MC, Girerd N. Semaglutide vs tirzepatide in patients with obesity and HFpEF: a report from a global federated research network. ESC Heart Fail. 2026;13(1):xvag042. doi:10.1093/eschf/xvag042. PMID:41711744.

Population: Adults with concurrent obesity and heart failure with preserved ejection fraction initiating semaglutide or tirzepatide.

Dose protocol: Propensity-score-matched observational comparison, 1,258 per group, median 24-week follow-up

Key findings: No difference between semaglutide and tirzepatide for composite of all-cause mortality and HF hospitalization (HR 1.14, 95% CI 0.89 to 1.46) in patients with obesity and HFpEF.

Notes: Early real-world cardiovascular safety signal. Short follow-up and observational design limit conclusions.