Effect of Obicetrapib on Glycaemia and New-Onset Diabetes

Objectives

New-onset diabetes (NoD) is a recognised effect of statin therapy potentially influencing acceptance of intensive LDL-C-lowering. In contrast, cholesteryl ester transfer protein (CETP) inhibition has been associated with lower NoD risk in earlier trials. We assessed the effect of the highly selective CETP inhibitor obicetrapib on glycaemia and NoD, contextualised within an updated meta-analysis of CETP inhibitor trials.

Methods

Individual participant data from the phase 3 BROADWAY and BROOKLYN trials were pooled across 1,700 participants without diabetes at baseline (899 normoglycaemic, 801 prediabetes; 38.8% women), randomised 2:1 to obicetrapib 10 mg or placebo for 52 weeks. The PRISMA-compliant, PROSPERO-registered systematic review identified six eligible trials reporting NoD. Pooled risk ratios were calculated using Mantel-Haenszel fixed-effect models, with prespecified subgroup analyses by baseline glycaemic status and CETPi potency, and trial-level meta-regression.

Results

Obicetrapib did not increase HbA1c at week 52 vs placebo (LSMD -0.02%, 95% CI -0.04 to 0.00). NoD occurred in 6.4% (obicetrapib) versus 8.5% (placebo) (adjusted OR 0.69, 95% CI 0.47-1.03), directionally consistent across glycaemic strata. Restricted cubic spline analyses identified associations between HDL-C, apoA1 and Lp(a) changes and NoD risk, but not HbA1c change. In the meta-analysis, CETP inhibition was associated with a 16% lower risk of NoD (RR 0.84, 95% CI 0.79-0.90; I2 = 0%).

Conclusions

Obicetrapib did not adversely affect glycaemia and was associated with a numerically lower risk of NoD, consistent with a CETP inhibitor class signal of a modestly lower risk. The PREVAIL trial will provide larger-longer evidence about obicetrapib and NoD.