Is Tirzepatide the New Game Changer in Type 2 Diabetes?
Abstract
:1. Background
2. Tirzepatide and Glucose Control
3. Tirzepatide and Body Weight
4. Tirzepatide and Cardiovascular Outcomes
5. Tirzepatide and Renal Outcomes
6. Safety
7. Ongoing Trials
8. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
List of Abbreviations
Cardiovascular | CV |
Cardiovascular disease | CVD |
Chronic kidney disease | CKD |
GLP-1 receptor agonists | GLP-1RAs |
Glucagon-like peptide 1 | GLP-1 |
Glucose-dependent insulinotropic polypeptide | GIP |
Glycated hemoglobin | HbA1c |
Randomized clinical trials | RCTs |
Sodium-glucose (co)transporter type 2 inhibitors | SGLT2is |
Tirzepatide | TZP |
Type 2 diabetes | T2D |
References
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Study (Year) | Study Duration (Weeks) | Intervention vs. Comparator | Randomization (Number of Participants) | Baseline Characteristics | Main Findings |
---|---|---|---|---|---|
SURPASS-1 (2021) | 40 | TZP vs. placebo (monotherapy in naïve T2D patients) | 1:1:1:1 TZP 5 mg qw (125) TZP 10 mg qw (125 pz) 15 mg qw (125 pz) Placebo qw (121 pz) | HbA1c 7.9% Mean age 54 yrs Women 48% Diabetes duration 4.7 yrs BMI 31.9 kg/m2 | Mean change from baseline in HbA1c: −1.87% with TZP 5 mg −1.89% with TZP 10 mg −2.07% with TZP 15 mg +0.04% with placebo |
% of participants achieving HbA1c < 7%: 87–92% with TZP 5–15 mg 20% with placebo | |||||
% of participants achieving HbA1c ≤ 6.5%: 81–86% with TZP 5–15 mg 10% with placebo | |||||
% of participants achieving HbA1c < 5.7%: 31–52% with TZP 5–15 mg 1% with placebo | |||||
Mean change in weight from baseline: −7 to −9.5 kg with TZP 5–15 mg | |||||
SURPASS-2 (2021) | 40 | TZP vs. semaglutide (T2D patients with poor glycemic control while on metformin) | 1:1:1:1 TZP 5 mg qw (470 pz) TZP 10 mg qw (469 pz) TZP 15 mg qw (470 pz) Semaglutide 1 mg qw (469 pz) | HbA1c 8.28% Mean age 56.6 yrs Women 53% Diabetes duration 8.6 yrs BMI 31.9 kg/m2 Waist 109.3 cm eGFR 96 mL/min | Mean change from baseline in HbA1c: −2.01% with TZP 5 mg −2.24% with TZP 10 mg −2.3% with TZP 15 mg −1.86% with semaglutide 1 mg |
% of participants achieving HbA1c < 7%: 82–86% with TZP 5–15 mg 79% with semaglutide 1 mg | |||||
% of participants achieving HbA1c ≤ 6.5%: 69–80% with TZP 5–15 mg 64% with semaglutide 1 mg | |||||
% of participants achieving HbA1c < 5.7%: 27–46% with TZP 5–15 mg 19% with semaglutide 1 mg | |||||
Mean change in weight from baseline: −7.6 to −11.2 kg with TZP 5–15 mg −5.7 kg with semaglutide 1 mg | |||||
SUPRASS-3 (2021) | 52 | TZP vs. insulin degludec U100 (add-on to metformin +/− sodium-glucose transporter 2 inhibitors) | 1:1:1:1 TZP 5 mg qw (361 pz) TZP 10 mg qw (361 pz) TZP 15 mg qw (361 pz) Insulin degludec U100 (361 pz) | HbA1c 8.17% Age ≥ 18 yrs Diabetes duration 8.4 yrs BMI > 25 kg/m2 | Mean change from baseline in HbA1c: −1.9% TZP 5 mg −2.2% TZP 10 mg −2.37% TZP 15 mg −1.34% insulin degludec U100 |
% of participants achieving HbA1c < 7%: 82–93% with TZP 5–15 mg 61% with insulin degludec U100 | |||||
Mean change in weight from baseline: −7.5 to −11.2 kg with TZP 5–15 mg +2.3 kg with insulin degludec U100 | |||||
SURPASS-4 (2021) | 52 | TZP vs. insulin glargine U100 (add-on to metformin +/− secretagogues +/− sodium- glucose transporter 2 inhibitors in any combinations in patients at high cardiovascular risk) | 1:1:1:3 TZP 5 mg qw (329 pz) TZP 10 mg qw (328 pz) TZP 15 mg qw (338 pz) Insulin glargine U100 (1000 pz) | HbA1c 8.5% Age ≥ 18 yrs Diabetes duration 11.8 yrs BMI > 25 kg/m2 | Mean change from baseline in HbA1c: −2.43% with TZP 10 mg −2.28% with TZP 15 mg −1.44% with insulin glargine U100 |
MACE-4 events (cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina): Hazard ratio = 0.74 (95% CI 0.51–1.08) | |||||
SURPASS-5 (2022) | 40 + 4 (4-week safety follow-up) | TZP vs. placebo (add-on to insulin glargine U100 of at least 20 IU per day or 0.25 IU/kg +/− metformin of at least 1500 mg per day) | 1:1:1:1 TZP 5 mg qw (116 pz) TZP 10 mg qw (119 pz) TZP 15 mg qw (120 pz) Placebo (120 pz) | HbA1c 8.3% Age ≥ 18 yrs BMI > 23 kg/m2 Diabetes duration 13.3 yrs Mean insulin dose 30 IU/day Women 44% | Mean change from baseline in HbA1c: −2.11% TZP 5 mg −2.40% TZP 10 mg −2.34% TZP 15 mg −0.86% placebo |
% of participants achieving HbA1c < 7%: 88%, pooled of TZP (all doses) 34.5% with placebo | |||||
% of participants achieving HbA1c ≤ 6.5%: 79%, pooled of TZP (all doses) 17.3% with placebo | |||||
% of participants achieving HbA1c < 5.7%: 38%, pooled of TZP (all doses) 3% with placebo | |||||
Mean change in weight from baseline: −5.4 to −8.8 kg with TZP 5–15 mg +1.6 kg with placebo | |||||
SURPASS-6 (2022) | 52 | TZP vs. insulin lispo U100 (add-on to basal-insulin glargine U100 +/− metformin of at least 1500 mg per day, sulphonylureas, or dipeptidyl peptidase type IV inhibitors) | 1:1:1:3 TZP 5 mg qw (243 pz) TZP 10 mg qw (238 pz) TZP 15 mg qw (236 pz) Insulin lipro U100 (708 pz) | HbA1c 8.8% Age ≥ 18 yrs BMI > 23 kg/m2 eGFR > 30 mL/min Women 57% Diabetes duration 14 yrs Median insulin dose 46 IU (0.53 IU/kg) | Mean change from baseline in HbA1c: −1.9% with TZP 5 mg −2.2% with TZP 10 mg −2.3% with TZP 15 mg −1.11% with insulin lispro U100 thrice a day |
% of participants achieving HbA1c < 7%: 68%, pooled TZP (all doses) 36% with insulin lispro U100 thrice a day | |||||
% of participants achieving HbA1c ≤ 6.5%: 56%, pooled TZP (all doses) 22% with insulin lispro U100 thrice a day | |||||
% of participants achieving HbA1c < 5.7%: 18%, pooled TZP (all doses) 3% with insulin lispro U100 thrice a day | |||||
Mean change in weight from baseline: −6.7 to −11 kg with TZP 5–15 mg +3.2 kg with insulin lispro U100 thrice a day |
Ongoing Trial (ClinicalTrial.Gov ID) | Sponsor | Kind of Study | Location(s) | Focus | Intervention/ Comparator | Start Date | Completion Date |
---|---|---|---|---|---|---|---|
NCT05536804 | Eli Lilly and Company | Phase II 56-week RCT | USA, Austria, Canada, Denmark, Mexico, Netherlands | Chronic kidney disease in T2D | TZP vs. placebo | 08 Feb 2023 | 26 Feb 2026 |
NCT04166773 | Eli Lilly and Company | Phase II RCT | USA, France, Italy, Japan, Mexico, Poland, Spain, UK | Nonalcoholic steatohepatitis | TZP vs. placebo | 19 Nov 2019 | 07 Feb 2024 |
NCT05751720 | Independent | Phase II nonrandomized, uncontrolled intervention trial | UAE (Abu Dhabi University) | Nonalcoholic fatty liver disease | TZP | Apr 2023 | Feb 2025 |
NCT04255433 | Eli Lilly and Company | SURPASS-CVOT, Phase III, active comparator RCT | USA, Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czech Republic, France, Germany, Greece, Hungary, India, Israel, Italy, Japan, Republic of Korea, Mexico, Netherlands, Poland, Puerto Rico, Russian Federation, Slovakia, Spain, Sweden, Taiwan, Turkey, Ukraine, UK | Major cardiovascular events in high-risk T2D | TZP vs. dulaglutide | 29 May 2020 | 17 Oct 2024 |
NCT05708859 | Independent | Phase IV RCT | USA (Torrance, California) | Progression of coronary atherosclerosis by using multidetector computed tomography | TZP vs. placebo | Dec 2023 | May 2026 |
NCT04847557 | Eli Lilly and Company | Phase III 52-week RCT | USA, Brazil, China, India, Israel, Mexico, Puerto Rico, Russian Federation, Taiwan | Heart failure with preserved ejection fraction in obesity | TZP vs. placebo | 20 Apr 2021 | 30 Jul 2024 |
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Lisco, G.; Disoteo, O.E.; De Geronimo, V.; De Tullio, A.; Giagulli, V.A.; Guastamacchia, E.; De Pergola, G.; Jirillo, E.; Triggiani, V. Is Tirzepatide the New Game Changer in Type 2 Diabetes? Endocrines 2024, 5, 72-86. https://doi.org/10.3390/endocrines5010005
Lisco G, Disoteo OE, De Geronimo V, De Tullio A, Giagulli VA, Guastamacchia E, De Pergola G, Jirillo E, Triggiani V. Is Tirzepatide the New Game Changer in Type 2 Diabetes? Endocrines. 2024; 5(1):72-86. https://doi.org/10.3390/endocrines5010005
Chicago/Turabian StyleLisco, Giuseppe, Olga Eugenia Disoteo, Vincenzo De Geronimo, Anna De Tullio, Vito Angelo Giagulli, Edoardo Guastamacchia, Giovanni De Pergola, Emilio Jirillo, and Vincenzo Triggiani. 2024. "Is Tirzepatide the New Game Changer in Type 2 Diabetes?" Endocrines 5, no. 1: 72-86. https://doi.org/10.3390/endocrines5010005
APA StyleLisco, G., Disoteo, O. E., De Geronimo, V., De Tullio, A., Giagulli, V. A., Guastamacchia, E., De Pergola, G., Jirillo, E., & Triggiani, V. (2024). Is Tirzepatide the New Game Changer in Type 2 Diabetes? Endocrines, 5(1), 72-86. https://doi.org/10.3390/endocrines5010005