CETP and SGLT2 inhibitor combination therapy increases glycemic control: a 2x2 factorial Mendelian randomization analysis.
Front Endocrinol (Lausanne)
; 15: 1359780, 2024.
Article
em En
| MEDLINE
| ID: mdl-38962682
ABSTRACT
Introduction:
Cholesteryl ester transfer protein (CETP) inhibitors, initially developed for treating hyperlipidemia, have shown promise in reducing the risk of new-onset diabetes during clinical trials. This positions CETP inhibitors as potential candidates for repurposing in metabolic disease treatment. Given their oral administration, they could complement existing oral medications like sodium-glucose cotransporter 2 (SGLT2) inhibitors, potentially delaying the need for injectable therapies such as insulin.Methods:
We conducted a 2x2 factorial Mendelian Randomization analysis involving 233,765 participants from the UK Biobank. This study aimed to evaluate whether simultaneous genetic inhibition of CETP and SGLT2 enhances glycemic control compared to inhibiting each separately.Results:
Our findings indicate that dual genetic inhibition of CETP and SGLT2 significantly reduces glycated hemoglobin levels compared to controls and single-agent inhibition. Additionally, the combined inhibition is linked to a lower incidence of diabetes compared to both the control group and SGLT2 inhibition alone.Discussion:
These results suggest that combining CETP and SGLT2 inhibitor therapies may offer superior glycemic control over SGLT2 inhibitors alone. Future clinical trials should investigate the potential of repurposing CETP inhibitors for metabolic disease treatment, providing an oral therapeutic option that could benefit high-risk patients before they require injectable therapies like insulin or glucagon-like peptide-1 (GLP-1) receptor agonists.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diabetes Mellitus Tipo 2
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Quimioterapia Combinada
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Proteínas de Transferência de Ésteres de Colesterol
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Análise da Randomização Mendeliana
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Inibidores do Transportador 2 de Sódio-Glicose
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Controle Glicêmico
Limite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Front Endocrinol (Lausanne)
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos