The class
Combining CETP and SGLT2 inhibition genetically improves glycaemic control beyond either alone (Front Endocrinol (Lausanne) 2024)
Original title: CETP and SGLT2 inhibitor combination therapy increases glycemic control: a 2x2 factorial Mendelian randomization analysis
Using a 2x2 factorial Mendelian randomisation analysis in 233,765 UK Biobank participants, researchers tested whether simultaneous genetic inhibition of CETP and SGLT2 improves glycaemic control more than inhibiting either target alone. Dual genetic inhibition of CETP and SGLT2 significantly reduced glycated haemoglobin compared with controls and with either single-agent inhibition, and was linked to a lower incidence of diabetes than both the control group and SGLT2 inhibition alone. The findings suggest combining CETP and SGLT2 inhibitor therapies, both oral, could offer superior glycaemic control to SGLT2 inhibitors alone and support future clinical trials repurposing CETP inhibitors as a metabolic disease treatment that might delay the need for injectable therapies.
Original 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.