TY - JOUR
T1 - Tirzepatide cardiovascular event risk assessment
T2 - a pre-specified meta-analysis
AU - Sattar, Naveed
AU - McGuire, Darren K.
AU - Pavo, Imre
AU - Weerakkody, Govinda J.
AU - Nishiyama, Hiroshi
AU - Wiese, Russell J.
AU - Zoungas, Sophia
N1 - Funding Information:
N.S. has consulted for or received lecture fees from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Hanmi Pharmaceuticals, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer and Sanofi and received grant support from AstraZeneca, Boehringer Ingelheim, Novartis and Roche Diagnostics through his institution, the University of Glasgow. D.K.M. reports personal fees from Boehringer Ingelheim, Janssen Research and Development, Sanofi US, Merck & Co., Merck Sharp & Dohme, Eli Lilly and Company, Novo Nordisk, GlaxoSmithKline, AstraZeneca, Lexicon Pharmaceuticals, Eisai, Pfizer, Metavant, Applied Therapeutics, Afimmune, Bayer and Esperion. S.Z. reports participation in advisory boards, expert committees or educational meetings on behalf of Monash University for Eli Lilly and Company, Boehringer Ingelheim, Sanofi, Servier, AstraZeneca, Novo Nordisk and Merck Sharp & Dohme Australia, outside of the submitted work. N.S., D.K.M. and S.Z. sit on the steering committee for the SURPASS-CVOT. I.P., R.J.W., G.J.W. and H.N. are employees and shareholders of Eli Lilly and Company.
Funding Information:
The authors thank C. A. Karanikas (Eli Lilly and Company) for writing and editorial assistance. This study was supported by Eli Lilly and Company. N.S. is supported by the British Heart Foundation Research Excellence Award (RE/18/6/34217).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/3
Y1 - 2022/3
N2 - Tirzepatide is a novel, once weekly, dual GIP/GLP-1 receptor agonist and is under development for the treatment of type 2 diabetes (T2D) and obesity. Its association with cardiovascular outcomes requires evaluation. This pre-specified cardiovascular meta-analysis included all seven randomized controlled trials with a duration of at least 26 weeks from the tirzepatide T2D clinical development program, SURPASS. The pre-specified primary objective of this meta-analysis was the comparison of the time to first occurrence of confirmed four-component major adverse cardiovascular events (MACE-4; cardiovascular death, myocardial infarction, stroke and hospitalized unstable angina) between pooled tirzepatide groups and control groups. A stratified Cox proportional hazards model, with treatment as a fixed effect and trial-level cardiovascular risk as the stratification factor, was used for the estimation of hazard ratios (HRs) and confidence intervals (CIs) comparing tirzepatide to control. Data from 4,887 participants treated with tirzepatide and 2,328 control participants were analyzed. Overall, 142 participants, 109 from the trial with high cardiovascular risk and 33 from the six trials with lower cardiovascular risk, had at least one MACE-4 event. The HRs comparing tirzepatide versus controls were 0.80 (95% CI, 0.57–1.11) for MACE-4; 0.90 (95% CI, 0.50–1.61) for cardiovascular death; and 0.80 (95% CI, 0.51–1.25) for all-cause death. No evidence of effect modifications was observed for any subgroups, although the evidence was stronger for participants with high cardiovascular risk. Tirzepatide did not increase the risk of major cardiovascular events in participants with T2D versus controls.
AB - Tirzepatide is a novel, once weekly, dual GIP/GLP-1 receptor agonist and is under development for the treatment of type 2 diabetes (T2D) and obesity. Its association with cardiovascular outcomes requires evaluation. This pre-specified cardiovascular meta-analysis included all seven randomized controlled trials with a duration of at least 26 weeks from the tirzepatide T2D clinical development program, SURPASS. The pre-specified primary objective of this meta-analysis was the comparison of the time to first occurrence of confirmed four-component major adverse cardiovascular events (MACE-4; cardiovascular death, myocardial infarction, stroke and hospitalized unstable angina) between pooled tirzepatide groups and control groups. A stratified Cox proportional hazards model, with treatment as a fixed effect and trial-level cardiovascular risk as the stratification factor, was used for the estimation of hazard ratios (HRs) and confidence intervals (CIs) comparing tirzepatide to control. Data from 4,887 participants treated with tirzepatide and 2,328 control participants were analyzed. Overall, 142 participants, 109 from the trial with high cardiovascular risk and 33 from the six trials with lower cardiovascular risk, had at least one MACE-4 event. The HRs comparing tirzepatide versus controls were 0.80 (95% CI, 0.57–1.11) for MACE-4; 0.90 (95% CI, 0.50–1.61) for cardiovascular death; and 0.80 (95% CI, 0.51–1.25) for all-cause death. No evidence of effect modifications was observed for any subgroups, although the evidence was stronger for participants with high cardiovascular risk. Tirzepatide did not increase the risk of major cardiovascular events in participants with T2D versus controls.
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U2 - 10.1038/s41591-022-01707-4
DO - 10.1038/s41591-022-01707-4
M3 - Article
C2 - 35210595
AN - SCOPUS:85125954761
VL - 28
SP - 591
EP - 598
JO - Nature Medicine
JF - Nature Medicine
SN - 1078-8956
IS - 3
ER -