Is Tirzepatide the New Game Changer in Type 2 Diabetes?
<b>Background:</b> Tirzepatide (TZP) is a once-weekly glucagon-like peptide 1 (GLP-1) and glucose-dependent-insulinotropic-polypeptide (GIP) receptor co-agonist approved for T2D. TZP provides promising evidence in improving glucose control and weight loss in T2D and obesity across precli...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-02-01
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| Series: | Endocrines |
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| Online Access: | https://www.mdpi.com/2673-396X/5/1/5 |
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| author | Giuseppe Lisco Olga Eugenia Disoteo Vincenzo De Geronimo Anna De Tullio Vito Angelo Giagulli Edoardo Guastamacchia Giovanni De Pergola Emilio Jirillo Vincenzo Triggiani |
| author_facet | Giuseppe Lisco Olga Eugenia Disoteo Vincenzo De Geronimo Anna De Tullio Vito Angelo Giagulli Edoardo Guastamacchia Giovanni De Pergola Emilio Jirillo Vincenzo Triggiani |
| author_sort | Giuseppe Lisco |
| collection | DOAJ |
| description | <b>Background:</b> Tirzepatide (TZP) is a once-weekly glucagon-like peptide 1 (GLP-1) and glucose-dependent-insulinotropic-polypeptide (GIP) receptor co-agonist approved for T2D. TZP provides promising evidence in improving glucose control and weight loss in T2D and obesity across preclinical and human studies, including data from the SURPASS program. <b>Aims:</b> The goal of this paper was to review the evidence on TZP in terms of glucose control, body weight, and the progression of chronic diabetes-related complications and comorbidities. <b>Results:</b> The mean change in HbA1c ranged from −1.6% to −2.06% over placebo, from −0.29% to −0.92% over each GLP-1RAs, and from −0.7% to −1.09% over basal insulins. In SURPASS-6, TZP was more effective than insulin lispro U100 added to basal insulin in reducing HbA<sub>1c</sub> levels at the study end (−2.1% vs. −1.1%, respectively). Compared to placebo, TZP induces a significant weight loss: 7.5 (5 mg/week); 11 (10 mg/week); and 12 kg (15 mg/week). Compared to GLP-1RAs, TZP reduces body weight from −1.68 kg to −7.16 kg depending on the dose (5 to 15 mg, respectively). Compared to basal insulin alone rigorously titrated, TZP added onto basal-insulin results in the best strategy for the composite endpoint of improvement of glucose control and weight loss. In SURPASS-6, TZP compared to insulin lispro U100 in add-on to insulin glargine U100 reduced body weight by 9 kg in mean (versus weight gain in basal-bolus users: +3.2 kg). TZP has pleiotropic effects potentially dampening the individual cardiovascular risk, including a reduction in systolic arterial pressure by 4 to 6 mmHg and total cholesterol by 4–6% compared to baseline. A post hoc analysis of SURPASS-4 revealed that TZP, compared to glargine U100, delayed the rate of glomerular filtration decline (−1.4 mL/min vs. −3.6 mL/min, respectively), reduced the rate of urinary albumin excretion (−6.8% vs. +36.9%, respectively), and was associated with a lower occurrence of the composite renal endpoint (HR 0.58 [0.43; 0.80]). <b>Conclusions:</b> Consistent evidence indicates that TZP dramatically changes the clinical course of T2D in different clinical scenarios. The efficacy and safety of TZP on chronic diabetes-related comorbidities and complications seem promising, but ongoing trials will clarify the real benefits. |
| first_indexed | 2024-04-24T18:21:44Z |
| format | Article |
| id | doaj.art-cd4aec6ccfcc40fc8b15cb0ffd31880c |
| institution | Directory Open Access Journal |
| issn | 2673-396X |
| language | English |
| last_indexed | 2024-04-24T18:21:44Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Endocrines |
| spelling | doaj.art-cd4aec6ccfcc40fc8b15cb0ffd31880c2024-03-27T13:35:16ZengMDPI AGEndocrines2673-396X2024-02-0151728610.3390/endocrines5010005Is Tirzepatide the New Game Changer in Type 2 Diabetes?Giuseppe Lisco0Olga Eugenia Disoteo1Vincenzo De Geronimo2Anna De Tullio3Vito Angelo Giagulli4Edoardo Guastamacchia5Giovanni De Pergola6Emilio Jirillo7Vincenzo Triggiani8Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari “Aldo Moro”, 70124 Bari, ItalyUnit of Endocrinology, Diabetology, Dietetics and Clinical Nutrition, Sant Anna Hospital, 22020 San Fermo della Battaglia, ItalyUnit of Endocrinology, Clinical Diagnostic Center Morgagni, 95100 Catania, ItalyInterdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari “Aldo Moro”, 70124 Bari, ItalyInterdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari “Aldo Moro”, 70124 Bari, ItalyInterdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari “Aldo Moro”, 70124 Bari, ItalyCenter of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS “Saverio de Bellis”, 70013 Castellana Grotte, ItalyInterdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari “Aldo Moro”, 70124 Bari, ItalyInterdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari “Aldo Moro”, 70124 Bari, Italy<b>Background:</b> Tirzepatide (TZP) is a once-weekly glucagon-like peptide 1 (GLP-1) and glucose-dependent-insulinotropic-polypeptide (GIP) receptor co-agonist approved for T2D. TZP provides promising evidence in improving glucose control and weight loss in T2D and obesity across preclinical and human studies, including data from the SURPASS program. <b>Aims:</b> The goal of this paper was to review the evidence on TZP in terms of glucose control, body weight, and the progression of chronic diabetes-related complications and comorbidities. <b>Results:</b> The mean change in HbA1c ranged from −1.6% to −2.06% over placebo, from −0.29% to −0.92% over each GLP-1RAs, and from −0.7% to −1.09% over basal insulins. In SURPASS-6, TZP was more effective than insulin lispro U100 added to basal insulin in reducing HbA<sub>1c</sub> levels at the study end (−2.1% vs. −1.1%, respectively). Compared to placebo, TZP induces a significant weight loss: 7.5 (5 mg/week); 11 (10 mg/week); and 12 kg (15 mg/week). Compared to GLP-1RAs, TZP reduces body weight from −1.68 kg to −7.16 kg depending on the dose (5 to 15 mg, respectively). Compared to basal insulin alone rigorously titrated, TZP added onto basal-insulin results in the best strategy for the composite endpoint of improvement of glucose control and weight loss. In SURPASS-6, TZP compared to insulin lispro U100 in add-on to insulin glargine U100 reduced body weight by 9 kg in mean (versus weight gain in basal-bolus users: +3.2 kg). TZP has pleiotropic effects potentially dampening the individual cardiovascular risk, including a reduction in systolic arterial pressure by 4 to 6 mmHg and total cholesterol by 4–6% compared to baseline. A post hoc analysis of SURPASS-4 revealed that TZP, compared to glargine U100, delayed the rate of glomerular filtration decline (−1.4 mL/min vs. −3.6 mL/min, respectively), reduced the rate of urinary albumin excretion (−6.8% vs. +36.9%, respectively), and was associated with a lower occurrence of the composite renal endpoint (HR 0.58 [0.43; 0.80]). <b>Conclusions:</b> Consistent evidence indicates that TZP dramatically changes the clinical course of T2D in different clinical scenarios. The efficacy and safety of TZP on chronic diabetes-related comorbidities and complications seem promising, but ongoing trials will clarify the real benefits.https://www.mdpi.com/2673-396X/5/1/5tirzepatidetype 2 diabetesglycemic controlweight losscardiovascular outcomesrenal outcomes |
| spellingShingle | Giuseppe Lisco Olga Eugenia Disoteo Vincenzo De Geronimo Anna De Tullio Vito Angelo Giagulli Edoardo Guastamacchia Giovanni De Pergola Emilio Jirillo Vincenzo Triggiani Is Tirzepatide the New Game Changer in Type 2 Diabetes? Endocrines tirzepatide type 2 diabetes glycemic control weight loss cardiovascular outcomes renal outcomes |
| title | Is Tirzepatide the New Game Changer in Type 2 Diabetes? |
| title_full | Is Tirzepatide the New Game Changer in Type 2 Diabetes? |
| title_fullStr | Is Tirzepatide the New Game Changer in Type 2 Diabetes? |
| title_full_unstemmed | Is Tirzepatide the New Game Changer in Type 2 Diabetes? |
| title_short | Is Tirzepatide the New Game Changer in Type 2 Diabetes? |
| title_sort | is tirzepatide the new game changer in type 2 diabetes |
| topic | tirzepatide type 2 diabetes glycemic control weight loss cardiovascular outcomes renal outcomes |
| url | https://www.mdpi.com/2673-396X/5/1/5 |
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