A Retrospective Observational Study Examining the Generalizability of Glucagon-Like Peptide 1 Receptor Agonist Cardiovascular Outcome Trials to the Real-World Population with Type 2 Diabetes in Spain: The REPRESENT Study

Romera, Irene; Artime, Esther; Ihle, Katharina; Díaz‐Cerezo, Silvia; de-Santos, Miriam Rubio; Prado, A. De; Cebrián-Cuenca, Ana M; Conget, Ignacio

doi:10.1007/s12325-022-02196-0

Cited by 3 publications

(4 citation statements)

References 18 publications

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“…Semaglutide has demonstrated superior efficacy in decreasing MACE in comparison to other GLP-1 RAs presently accessible in the market, except for lixisenatide, where the contrast was insignificant. Previous retrospective studies suggested that the SUSTAIN-6 trial population may not adequately represent the real-world T2DM population in the United States, Spain, China, and the United Kingdom [ 49 – 52 ]. A meta-regression analysis shows that the cardiovascular benefits of GLP-1 RAs are linked to their beneficial effects on glycemic control [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Glycemic Control, Weight Management, Cardiovascular Safety, and Cost-Effectiveness of Semaglutide for Patients with Type 2 Diabetes Mellitus: A Rapid Review and Meta-analysis of Real-World Studies

Wang,

Wang

et al. 2024

Diabetes Ther

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Introduction Semaglutide is a high-profile glucose-lowering drug that medical decision-makers have acknowledged in recent years. This rapid review aims to provide evidence-based clinical recommendations for the treatment of type 2 diabetes mellitus (T2DM) with semaglutide. Methods We conducted a rapid review of randomized controlled trial (RCT)-based meta-analyses (MAs) and systematic reviews (SRs) of cost-effectiveness analyses (CEAs) compared to other glucagon-like peptide-1 receptor agonists (GLP-1 RAs) or placebo in patients with T2DM. Prospective cohort real-world studies (RWS) were also retrieved and subjected to MA. Four databases, including PubMed, the Cochrane Library, Embase, and ISPOR, were searched from inception to 5 March 2023. The outcomes of interest were hemoglobin A1c (HbA1c), body weight, major adverse cardiovascular events (MACE), and economic outcomes such as quality-adjusted life-years and total cost. Results We identified 33 publications: 22 RCT-based MAs, 1 SR of CEAs, and 10 RWS. Evidence showed that semaglutide at usual doses was associated with superior reductions in HbA1c and weight compared to most GLP-1 RAs in patients with T2DM who were drug naive, receiving basal insulin, or using oral hypoglycemic agents, and it was also associated with a lower number of MACE and was more cost-effective. Further, once-weekly semaglutide resulted in a significant reduction in HbA1c levels (−1.1%) and body weight (−4.88 kg) in routine clinical practice. Conclusions This review consolidates the positive current evidence base for prescribing semaglutide to patients with T2DM, but further rigorous studies are still urgently required to develop practice guidelines as innovative drugs become commercially available. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-023-01520-3.

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Section: Discussionmentioning

confidence: 99%

Glycemic Control, Weight Management, Cardiovascular Safety, and Cost-Effectiveness of Semaglutide for Patients with Type 2 Diabetes Mellitus: A Rapid Review and Meta-analysis of Real-World Studies

Wang,

Wang

et al. 2024

Diabetes Ther

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“…Additionally, research on the association between TRβ and NAFLD, which may involve the intrinsic mechanism of NAFLD development, remains insufficient. Liraglutide is a GLP-1R agonist (GLP-1RA) that enhances meal-stimulated insulin secretion and reduces glucagon secretion, gastric emptying, intestinal lipoprotein secretion, food intake, and body weight, thereby improving the metabolic health of animals and humans [23,24]. Data from animal studies and randomized human trials indicate reductions in liver fat, fibrosis, and inflammation after sustained GLP-1RA administration through mechanisms that have not been fully elucidated [25,26].…”

Section: Discussionmentioning

confidence: 99%

Effect of Liraglutide on Serum TSH Levels in Patients with NAFLD and its Underlying Mechanisms

Wen

et al. 2022

International Journal of Clinical Practice

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This study aimed to evaluate the effect of liraglutide on serum thyroid-stimulating hormone (TSH) levels in patients with type 2 diabetes mellitus (T2DM) and explore the underlying mechanisms via bioinformatics analysis. A total of 49 obese/overweight patients with T2DM received liraglutide during outpatient visits or hospitalization in the Department of Endocrinology. Meanwhile, the control group included 49 patients with T2DM but without nonalcoholic fatty liver disease (NAFLD) who were matched for age and sex (baseline from July 2016 to June 2021). Follow-up data on the last use of liraglutide were also retrieved. Age, sex, body mass index (BMI), and duration of diabetes were obtained from the participants’ records. All patients were tested for biochemical markers hemoglobin A1c (HbA1c), alanine transaminase, aspartate transaminase, free triiodothyronine, free thyroxine (FT4), and TSH at baseline and follow-up. After adjusting for all factors with a p -value < 0.05, BMI, HbA1c, LDL, FT4, and TSH were identified as significant independent risk factors for NAFLD in the univariate analysis. Following liraglutide therapy (average time 16 months), these patients had significantly lower BMI, HbA1c, and TSH but higher high-density lipoprotein (HDL) levels than those in the baseline data (all p < 0.05), and further subgroup analysis stratified by duration of liraglutide use showed that the test for time trends had statistical differences in BMI and TSH but not in HbA1c and HDL. After the therapy, the NAFLD and NASH groups showed significantly decreased TSH levels after liraglutide therapy compared with the corresponding baseline data. Furthermore, the expression of THRB, which encodes TRβ, was significantly decreased in the NAFLD group, which may explain the thyroid hormone resistance-like manifestation in the clinical findings. In conclusion, liraglutide improves hepatic thyroid hormone resistance in T2DM with NAFLD, and restoration of impaired TRβ expression in NAFLD is a potential mechanism involved in the process of liraglutide therapy.

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“…Because of such strict methodology, the populations included in CVOTs may not be representative of the general diabetes population. When the clinical characteristics of participants in the LEADER, REWIND and SUSTAIN-6 trials were compared with the typical diabetes population in Spain [ 30 ], the UK [ 31 ] and the USA [ 32 ], even the most representative of these CVOTs (REWIND) captured only a fraction (42.6–53.6%) of the real-world type 2 diabetes population (Fig. 3 ).…”

Section: Real-world Evidence Of Glp-1ra Effects On Cvdmentioning

confidence: 99%

“…3 Generalisability of results from GLP-1RA CVOTs to the real-world type 2 diabetes population. The infographic shows the proportion of individuals in the general adult type 2 diabetes population from Spain [ 30 ], the UK [ 31 ], and the USA [ 32 ] that would have been eligible for enrolment in the LEADER [ 17 ], SUSTAIN-6 [ 18 ] and REWIND [ 25 ] trials (sorted by publication date) according to the trials’ key selection criteria. General population with type 2 diabetes, grey; eligible individuals for study enrolment, blue.…”

Section: Real-world Evidence Of Glp-1ra Effects On Cvdmentioning

confidence: 99%

Incretins and cardiovascular disease: to the heart of type 2 diabetes?

2023

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Major cardiovascular outcome trials and real-life observations have proven that glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs), regardless of structural GLP-1 homology, exert clinically relevant cardiovascular protection. GLP-1RAs provide cardioprotective benefits through glycaemic and non-glycaemic effects, including improved insulin secretion and action, body-weight loss, blood-pressure lowering and improved lipid profile, as well as via direct effects on the heart and vasculature. These actions are likely combined with anti-inflammatory and antioxidant properties that translate into robust and consistent reductions in atherothrombotic events, particularly in people with type 2 diabetes and established atherosclerotic CVD. GLP-1RAs may also have an impact on obesity and chronic kidney disease, conditions for which cardiovascular risk-reducing options are limited. The available evidence has prompted professional and medical societies to recommend GLP-1RAs for mitigation of the cardiovascular risk in people with type 2 diabetes. This review summarises the clinical evidence for cardiovascular protection with use of GLP-1RAs and the main mechanisms underlying this effect. Moreover, it looks into how the availability of upcoming dual and triple incretin receptor agonists might expand the possibility for cardiovascular protection in people with type 2 diabetes. Graphical Abstract

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A Retrospective Observational Study Examining the Generalizability of Glucagon-Like Peptide 1 Receptor Agonist Cardiovascular Outcome Trials to the Real-World Population with Type 2 Diabetes in Spain: The REPRESENT Study

Cited by 3 publications

References 18 publications

Glycemic Control, Weight Management, Cardiovascular Safety, and Cost-Effectiveness of Semaglutide for Patients with Type 2 Diabetes Mellitus: A Rapid Review and Meta-analysis of Real-World Studies

Glycemic Control, Weight Management, Cardiovascular Safety, and Cost-Effectiveness of Semaglutide for Patients with Type 2 Diabetes Mellitus: A Rapid Review and Meta-analysis of Real-World Studies

Effect of Liraglutide on Serum TSH Levels in Patients with NAFLD and its Underlying Mechanisms

Incretins and cardiovascular disease: to the heart of type 2 diabetes?

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