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. 2024 Jan 3;23(1):4.
doi: 10.1186/s12933-023-02077-y.

Impact of PCSK9 inhibitors in glycaemic control and new-onset diabetes

Ana M González-Lleó  1   2 , Rosa M Sánchez-Hernández  3   4 , Núria Plana  5 , Daiana Ibarretxe  5 , Pere Rehues  5 , Josep Ribalta  5 , Dídac Llop  5 , Ana M Wägner  3   4 , Lluís Masana  5 , Mauro Boronat  3   4
Affiliations

Impact of PCSK9 inhibitors in glycaemic control and new-onset diabetes

Ana M González-Lleó et al. Cardiovasc Diabetol. .

Abstract

Background: The diabetogenic effect of statins has been well established by clinical trials, Mendelian randomisation studies and meta-analyses. According to large clinical trials, PCSK9 inhibitors (PCSK9i) have no deleterious impact on glucose metabolism. However, few real-life studies have yet evaluated the long-term effects of these drugs on glucose homeostasis and their impact on new-onset diabetes (NODM).

Methods: We studied 218 patients treated with either alirocumab or evolocumab (70% with familial hypercholesterolemia) for at least three years (PCSK9iG). We studied the NODM rate in the nondiabetic group at baseline (168) and overall glucose metabolism control in the whole group. Incidental DM was compared with two groups. The first was a propensity score matching (PSM)-selected group (n = 168) from the database of patients attending the Reus lipid unit (Metbank, n = 745) who were not on PCSK9i (PSMG). The second was a subgroup with a similar age range (n = 563) of the Di@bet.es study (Spanish prospective study on diabetes development n = 5072) (D@G). The incidence was reported as the percentage of NODM cases per year.

Results: The fasting glucose (FG) level of the subjects with normoglycaemia at baseline increased from 91 (86-95.5) to 93 (87-101) mg/dL (p = 0.014). There were 14 NODM cases in the PCSK9i group (2.6%/y), all among people with prediabetes at baseline. The incidence of NODM in PSMG and D@G was 1.8%/y (p = 0.69 compared with the PCSK9iG). The incidence among the subjects with prediabetes was 5.1%/y in the PCSK9iG, 4.8%/y in the PSMG and 3.9%/y in the D@G (p = 0.922 and p = 0.682, respectively). In the multivariate analysis, only the FG level was associated with the development of NODM in the PCSK9iG (OR 1.1; 95% CI: 1.0-1.3; p = 0.027). Neither FG nor A1c levels changed significantly in patients with DM at baseline.

Conclusion: A nonsignificant increase in NODM occurred in the PCSK9iG, particularly in patients with prediabetes, compared with the PSMG and D@G groups. Baseline FG levels were the main variable associated with the development of DM. In the subjects who had DM at baseline, glucose control did not change. The impact of PCSK9i on glucose metabolism should not be of concern when prescribing these therapies.

Keywords: Familial hypercholesterolemia; Hyperglycaemia; New-onset Diabetes Mellitus; PCSK9 inhibitors; Prediabetes; Real-life study.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Incidence (%/year) of new onset Diabetes Mellitus according to their original group PCSK9iG: PCSK9i users; PSMG: Propensity score matching group (control group 1); D@G: di@bet.es cohort (control group 2); FH: familial hypercholesterolemia group
Fig. 2
Fig. 2
Evolution of fasting glucose, A1c and BMI in DM patients at baseline on PCSK9i Follow-up 3.2 years. Only significant differences were found in BMI A1c: glycated haemoglobin. BMI: body mass index. NS: not significant
See this image and copyright information in PMC

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