Tirzepatide: A Systematic Update
Abstract
:1. Introduction
2. Tirzepatide in the SURPASS Trials
3. Tirzepatide and Obesity: The SURMOUNT-1 Trial
4. Tirzepatide and Hypertension
5. Data from Meta-Analyses
6. New Perspectives
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Outcomes | Tirzepatide 5 mg (n = 121) | Tirzepatide 10 mg (n = 121) | Tirzepatide 15 mg (n = 120) | Placebo (n = 113) | |
---|---|---|---|---|---|
HbA1c (%) | Baseline | 7.97 | 7.88 | 7.88 | 8.08 |
From baseline | −1.87 * | −1.89 * | −2.07 * | 0.04 ** | |
Versus placebo | −1.91 * | −1.93 * | −2.11 * | - | |
Weight (Kg) | From baseline | −7.0 * | −7.8 * | −9.5 * | −0.7 *** |
Versus placebo | −6.3 * | −7.1 * | −8.8 * | - |
Outcomes | Tirzepatide 5 mg (n = 470) | Tirzepatide 10 mg (n = 469) | Tirzepatide 15 mg (n = 470) | Semaglutide (n = 469) | |
---|---|---|---|---|---|
HbA1c (%) | Baseline | 8.32 | 8.30 | 8.26 | 8.25 |
From baseline | −2.01 | −2.24 | −2.30 | −1.86 | |
Versus Semaglutide | −0.15 ** | −0.39 * | −0.45 * | - | |
Weight (Kg) | From baseline | −7.6 | −9.3 | −11.2 | −5.7 |
Versus Semaglutide | −1.9 * | −3.6 * | −5.5 * | - |
Outcomes | Tirzepatide 5 mg (n = 358) | Tirzepatide 10 mg (n = 360) | Tirzepatide 15 mg (n = 358) | Insulin Degludec (n = 359) | |
---|---|---|---|---|---|
HbA1c (%) | Baseline | 8.17 | 8.19 | 8.21 | 8.13 |
From baseline | −1.93 | −2.20 | −2.37 | −1.34 | |
Versus insulin degludec | −0.59 * | −0.86 * | −1.04 * | - | |
Weight (Kg) | From baseline | −7.5 | −10.7 | −12.9 | 2.3 |
Versus insulin degludec | −9.8 * | −13 * | −15.2 * | - |
Outcomes | Tirzepatide 5 mg (n = 326) | Tirzepatide 10 mg (n = 321) | Tirzepatide 15 mg (n = 334) | Insulin Glargine (n = 978) | |
---|---|---|---|---|---|
HbA1c (%) | Baseline | 8.52 | 8.60 | 8.52 | 8.51 |
From baseline | −2.24 | −2.43 | −2.58 | −1.44 | |
Versus insulin glargine | −0.80 * | −0.99 * | −1.14 * | ||
Weight (Kg) | From baseline | −7.1 | −9.5 | −11.7 | 1.9 |
Versus insulin glargine | −9.0 * | −11.4 * | −13.5 * |
Outcomes | Tirzepatide 5 mg (n= 116) | Tirzepatide 10 mg (n= 119) | Tirzepatide 15 mg (n= 120) | Placebo (n= 120) | |
---|---|---|---|---|---|
HbA1c (%) | Baseline | 8.30 | 8.36 | 8.22 | 8.38 |
From baseline | −2.11 | −2.40 | −2.34 | −0.86 | |
Versus placebo | −1.24 * | −1.53 * | −1.47 * | ||
Weight (Kg) | From baseline | −5.4 | −7.5 | −8.8 | 1.6 |
Versus placebo | −7.1 * | −9.1 * | −10.5 * |
Outcomes | Tirzepatide 5 mg (n = 630) | Tirzepatide 10 mg (n = 636) | Tirzepatide 15 mg (n = 630) | Placebo (n = 643) | |
---|---|---|---|---|---|
Body Weight (Kg) | Baseline | 102.9 | 105.8 | 105.6 | 104.8 |
From baseline (%) | −15 | −19.5 | −20.9 | −3.1 | |
Versus placebo (%) | −11.9 * | −16.4 * | −17.8 * | ||
Waist circumference (cm) | From baseline | −14 | −17.7 | −18.5 | −4 |
Versus placebo | −10.1 * | −13.8 * | −14.5 * |
Nausea (%) | Diarrhea (%) | Vomiting (%) | |
---|---|---|---|
SURPASS-1 | 12–18 | 12–14 | 2–6 |
SURPASS-2 | 17–22 | 13–16 | 6–10 |
SURPASS-3 | 12–24 | 15–17 | 6–10 |
SURPASS-4 | 12–23 | 13–22 | 5–9 |
SURPASS-5 | 13–18 | 12–21 | 7–13 |
SURMOUNT-1 | 25–33 | 19–23 | 8–12 |
SYNERGY-NASH (phase II) | A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study Comparing the Efficacy and Safety of Tirzepatide Versus Placebo in Patients with Nonalcoholic Steatohepatitis (NASH). |
SURPASS-CVOT (phase III) | The Effect of Tirzepatide Versus Dulaglutide on Major Adverse Cardiovascular Events in Patients with Type 2 Diabetes. |
SURPASS-PEDS (phase III) | Efficacy, Safety, and Pharmacokinetics/Pharmacodynamics of Tirzepatide in Pediatric and Adolescent Participants with Type 2 Diabetes Mellitus Inadequately Controlled with Metformin, or Basal Insulin, or Both. |
SURPASS-6 (phase III) | The Effect of the Addition of Tirzepatide Once Weekly Versus Insulin Lispro Three Times Daily in Participants with Type 2 Diabetes Inadequately Controlled on Insulin Glargine (U100) with or without Metformin. |
SURMOUNT-2 (phase III) | Efficacy and Safety of Tirzepatide Once Weekly in Participants with Type 2 Diabetes Who Have Obesity or Are Overweight. |
SURMOUNT-3 (phase III) | Efficacy and Safety of Tirzepatide Once Weekly Versus Placebo After an Intensive Lifestyle Program in Participants without Type 2 Diabetes Who Have obesity or Are Overweight with Weight-Related Comorbidities. |
SURMOUNT-4 (phase III) | Efficacy and Safety of Tirzepatide Once Weekly Versus Placebo for Maintenance of Weight Loss in Participants Without Type 2 Diabetes Who Have Obesity or Are Overweight with Weight-Related Comorbidities: A Randomized, Double-Blind, Placebo-Controlled Trial. |
SURMOUNT-CN (phase III) | Efficacy and Safety of Tirzepatide Once Weekly in Chinese Participants Without Type 2 Diabetes Who Have Obesity or Are Overweight with Weight-Related Comorbidities: A Randomized, Double-Blind, Placebo-Controlled Trial. |
SURMOUNT-J (phase III) | Efficacy and Safety of Once-Weekly Tirzepatide in Participants with Obesity Disease. |
SUMMIT (phase III) | Study Comparing the Efficacy and Safety of Tirzepatide Versus Placebo in Patients with Heart Failure with Preserved Ejection Fraction and Obesity. |
SURPASS-EARLY (phase IV) | Study to Evaluate the Long-Term Efficacy and Safety of Tirzepatide Compared with Intensified Conventional Care in Adults When Initiating Treatment Early in the Course of Type 2 Diabetes. |
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Forzano, I.; Varzideh, F.; Avvisato, R.; Jankauskas, S.S.; Mone, P.; Santulli, G. Tirzepatide: A Systematic Update. Int. J. Mol. Sci. 2022, 23, 14631. https://doi.org/10.3390/ijms232314631
Forzano I, Varzideh F, Avvisato R, Jankauskas SS, Mone P, Santulli G. Tirzepatide: A Systematic Update. International Journal of Molecular Sciences. 2022; 23(23):14631. https://doi.org/10.3390/ijms232314631
Chicago/Turabian StyleForzano, Imma, Fahimeh Varzideh, Roberta Avvisato, Stanislovas S. Jankauskas, Pasquale Mone, and Gaetano Santulli. 2022. "Tirzepatide: A Systematic Update" International Journal of Molecular Sciences 23, no. 23: 14631. https://doi.org/10.3390/ijms232314631