Impact of a dual glucose‐dependent insulinotropic peptide/<scp>glucagon‐like peptide</scp>‐1 receptor agonist tirzepatide on heart rate among patients with type 2 diabetes: A systematic review and pairwise and network meta‐analysis

Yang, Yucheng; He, Liyun; Liu, Peng; Wang, Jialu; Yang, Na; Li, Ziyi; Ping, Fan; Xu, Lingling; Li, Wei; Zhang, Huabing; Li, Yuxiu

doi:10.1111/dom.15342

Cited by 3 publications

(1 citation statement)

References 45 publications

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“…The weekly 15 mg dose had the most significant effect on increasing heart rate compared with lower doses of TZP and other treatments. The clinical relevance of this phenomenon is still unknown [75].…”

Section: Safetymentioning

confidence: 99%

Is Tirzepatide the New Game Changer in Type 2 Diabetes?

Lisco,

Disoteo,

De Geronimo

et al. 2024

Endocrines

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Background: 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. Aims: 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. Results: 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 HbA1c 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]). Conclusions: 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.

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Section: Safetymentioning

confidence: 99%

Is Tirzepatide the New Game Changer in Type 2 Diabetes?

Lisco,

Disoteo,

De Geronimo

et al. 2024

Endocrines

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A comment on tirzepatide versus glucagon‐like peptide‐1 receptor agonists and heart rate with regard to ‘Impact of a dual glucose‐dependent insulinotropic peptide/glucagon‐like peptide‐1 receptor agonist tirzepatide on heart rate among patients with type 2 diabetes: A systematic review and pairwise and network meta‐analysis’

Goldenberg

2023

Diabetes Obesity Metabolism

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Dear Editor, I congratulate Yang et al. 1 on their systematic review and metaanalysis on the impact of tirzepatide (TZP) on the change in heart rate from baseline compared with control groups, including glucagon-like peptide-1 receptor agonists (GLP-1RAs). GLP-1RAs have been shown to increase the heart rate by approximately two beats per minute compared with placebo or other antihyperglycaemic agents. 2 There is also evidence indicating that glucose-dependent insulinotropic polypeptide (GIP) may increase the heart rate. 3 Because TZP is a dual GLP-1/GIP receptor agonist, it is important to understand the impact of this agent on the change in heart rate and whether it differs from the effect of GLP-1RAs.In a pairwise meta-analysis of randomized controlled trials, Yang

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Tirzepatide cardiovascular benefits and adverse events assessment: a Bayesian network meta-analysis

gong,

cheng,

han

et al. 2024

Preprint

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Objective To comprehensively assess the cardiovascular benefits and adverse events of tirzepatide (including different control groups, different dosages and different patients). Method A systematic search was conducted on PubMed, Web of Science,The Cochrane Library and ClinicalTrials.gov. Randomized controlled trials (RCTs) of at least 26 weeks that compared tirzepatide (TZP) at doses of 5mg, 10mg, and 15 mg once weekly with another antihyperglycemic drug or placebo in adults with obesity or type 2 dabetes mellitus(T2DM) were included. Data Synthesis was performed using R 4.2.2 and Stata 18.0 software. Each outcome was presented as a relative risk (RR) with a 95% confidence interval (CI). The results were also displayed using network plots, the surface under the cumulative ranking curve value (SUCRA), league table and forest plot. Results A total of 14 RCTs with 14654 participants with T2DM or obesity were included inthis study. Generally, compared to placebo, insulin and glucagon-like peptide-1 receptor agonists (GLP-1RAs), TZP did not increase the risk of four-component major adverse cardiovascular events (MACE-4) (RR [95% CI], 0.54[0.25 to 1.06], 0.85 [0.45 to 1.81], 1.00 [0.34 to 2.92], respectively) and significantly increased total adverse events(TAEs)(RR[95% CI], 1.09[1.01,1.19], 1.22 [1.11,1.35], 1.03 [0.91,1.16], respectively). Compared to placebo, TZP 5mg, TZP 10mg and TZP 15mg all reduced the incidence of MACE-4 (RR [95% CI], 0.47 [0.23 to 1.12], 0.46 [0.15 to 1.48], 0.38 [0.17 to 0.84], respectively) and increased the risk of TAEs (RR[95% CI] 1.04[0.96,1.13], 1.07[0.99,1.16], 1.10[1.02,1.19], respectively). Compared to GLP-1 RAs, TZP 5 mg, TZP 10 mg, and TZP 15 mg all increased the risk of TAEs(RR [95% CI], 1.01[0.91,1.11], 1.04[0.94,1.14], 1.07[0.97,1.17], respectively) and TZP 15mg reduced the risk of MACE-4 (0.82 [0.31 to 2.22]). Compared to obesity, patients with T2DM experienced greater benefits of MACE-4 (RR[95% CI], 0.44[0.04 to 2.65])and lower risk of TAEs (RR [95% CI], 0.95 [0.77 to 1.24]). Additionlay, TZP reduced all-cause death (ACD) and serious adverse events(SAEs) but increased the risk of DAEs. And these benefits were not superior to those of GLP-1RAs, while the risk of adverse events leading to discontinuation of study treatment (DAEs) was higher than that of GLP-1RAs. TZP 15mg was more effective in reducing ACD and SAEs, but also increased the risk of discontinuation. among patients who use TZP, T2DM patients had greater benefits in ACD and less risk of SAEs and DAEs compared to obeity patients. Conclusions TZP is not inferior to GLP-1 RAs in reducing cardiovascular events. The effect is greater with TZP 15mg, but there are also more adverse events. Additionally, the use of TZP in T2DM patients may have a greater effect and fewer adverse events than in obesity patients.

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Impact of a dual glucose‐dependent insulinotropic peptide/glucagon‐like peptide‐1 receptor agonist tirzepatide on heart rate among patients with type 2 diabetes: A systematic review and pairwise and network meta‐analysis

Cited by 3 publications

References 45 publications

Is Tirzepatide the New Game Changer in Type 2 Diabetes?

Is Tirzepatide the New Game Changer in Type 2 Diabetes?

Tirzepatide cardiovascular benefits and adverse events assessment: a Bayesian network meta-analysis

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