Efficacy and safety of the dual GIP and GLP-1 receptor agonist tirzepatide for weight loss: a meta-analysis of randomized controlled trials

Mesquita, Yasmin Luz Lima de; Calvi, Izabela Pera; Marques, Isabela Reis; Cruz, Sara A.; Padrão, Eduardo Messias Hirano; Carvalho, Pedro E P; Silva, Caroliny Hellen Azevedo da; Cardoso, Rhanderson; Moura, Filipe A.; Rafalskiy, Vladimir V.

doi:10.1038/s41366-023-01337-x

Cited by 19 publications

(8 citation statements)

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“…Clinical trials indicate that dual GLP-1/GIP co-agonists, such as tirzepatide, should be considered the most effective agents compared to other antihyperglycemic drugs in the early stage as well as long-lasting T2D [ 199 , 200 , 201 , 202 , 203 , 204 ]. Clinical trials and meta-analyses also indicated that tirzepatide, compared to placebo, reduces body weight by 7.5 to 12 kg (5 to 15 mg/weekly) and 1.7 to 7.2 kg compared to GLP-1RAs [ 205 , 206 ]. Ongoing investigations confirm these impressive results on weight loss also in obese individuals.…”

Section: Preventing Sarcopenia: a Therapeutic Target In Primary And S...mentioning

confidence: 99%

Sarcopenia and Diabetes: A Detrimental Liaison of Advancing Age

Lisco,

Disoteo,

De Tullio

et al. 2023

Nutrients

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Sarcopenia is an age-related clinical complaint characterized by the progressive deterioration of skeletal muscle mass and strength over time. Type 2 diabetes (T2D) is associated with faster and more relevant skeletal muscle impairment. Both conditions influence each other, leading to negative consequences on glycemic control, cardiovascular risk, general health status, risk of falls, frailty, overall quality of life, and mortality. PubMed/Medline, Scopus, Web of Science, and Google Scholar were searched for research articles, scientific reports, observational studies, clinical trials, narrative and systematic reviews, and meta-analyses to review the evidence on the pathophysiology of di-abetes-induced sarcopenia, its relevance in terms of glucose control and diabetes-related outcomes, and diagnostic and therapeutic challenges. The review comprehensively addresses key elements for the clinical definition and diagnostic criteria of sarcopenia, the pathophysiological correlation be-tween T2D, sarcopenia, and related outcomes, a critical review of the role of antihyperglycemic treatment on skeletal muscle health, and perspectives on the role of specific treatment targeting myokine signaling pathways involved in glucose control and the regulation of skeletal muscle metabolism and trophism. Prompt diagnosis and adequate management, including lifestyle inter-vention, health diet programs, micronutrient supplementation, physical exercise, and pharmaco-logical treatment, are needed to prevent or delay skeletal muscle deterioration in T2D.

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Section: Preventing Sarcopenia: a Therapeutic Target In Primary And S...mentioning

confidence: 99%

Sarcopenia and Diabetes: A Detrimental Liaison of Advancing Age

Lisco,

Disoteo,

De Tullio

et al. 2023

Nutrients

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“…A meta analysis by Yasmin Luz Lima de Mesquita et al statemented more notable bodyweight reduction with tirzepatide 5 mg, 10mg and 15 mg than placebo [42] . As reported by previous network meta analysis, tirzepatide administered at all doses demonstrated higher weight loss effectiveness in comparison with with glargine, degludec.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of different doses of tirzepatide in patients with type 2 diabetes mellitus: a systematic review and network meta-analysis

Zhu,

Huang,

Luo

et al. 2024

Preprint

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Introduction: This study aims to evaluate the effectiveness and safety of different doses of tirzepatide on hypoglycemic, weight-loss, improvement of beta-cell function and insulin resistance in patients with type 2 diabetes mellitus compared with other glucose-lowering drugs or placebo. Research Design and Methods: Searches were conducted for PubMed, Cochrane Library, Web of Science and Embase for randomized controlled trials (RCTs) of tirzepatide from their inception to 2023. The network meta-analysis followed the PRISMA guidelines. Based on the Cochrane risk of bias tool, we analyzed the included RCTs using Stata 15.1. The standardized mean difference and surface under the cumulative ranking curve were presented for each result. An evaluation of publication bias was conducted using funnel plots. Results: Data from 17 studies involving 10405 patients was analyzed. Tirzepatide 10 mg and 15 mg were more effective at hypoglycemic control and weight loss than basal insulin (glargine or degludec) or GLP-1RAs (dulaglutide or semaglutide). Tirzepatide 15mg plays a leading role in lowering body weight (SCURA probability: 98.3%), fasting insulin (95.4%), fasting C-Peptide (91.8%), fasting blood glucose (88.2%) and glycated hemoglobin (85.7%). As for safety, 7407 (72%) had at least one treatment-emergent adverse events and most of that were gastrointestinal adverse events. Conclusions: Tirzepatide 15 mg, not only exhibited a favorable hypoglycemic and weight-loss efficacy, but also achieve a reduction of fasting insulin and fasting C-Peptide by comparison with insulin and GLP1-RAs. It is need of more well-designed RCTs to evaluate potential benefits on insulin resistance and pancreatic beta cell function of tirzepatide.

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“…The results of two meta-analyses showed that TZP induces a significant weight loss, compared to placebo by around 7.5 (5 mg/week), 11 (10 mg/week), and 12 kg (15 mg/week) [17,18]. 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) [14].…”

Section: Tirzepatide and Body Weightmentioning

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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Efficacy and safety of the dual GIP and GLP-1 receptor agonist tirzepatide for weight loss: a meta-analysis of randomized controlled trials

Cited by 19 publications

References 35 publications

Sarcopenia and Diabetes: A Detrimental Liaison of Advancing Age

Sarcopenia and Diabetes: A Detrimental Liaison of Advancing Age

Efficacy and safety of different doses of tirzepatide in patients with type 2 diabetes mellitus: a systematic review and network meta-analysis

Is Tirzepatide the New Game Changer in Type 2 Diabetes?

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