Effect of Switching from Low-Dose Simvastatin to High-Dose Atorvastatin on Glucose Homeostasis and Cognitive Function in Type 2 Diabetes

Abstract

Background

High-intensity statin is recommended in high-risk type 2 diabetes (T2D); however, statin dose dependently increases the risk of developing new-onset diabetes, can potentially worsen glycemic control in T2D, and may cause cognitive impairment. This study aimed to investigate the effect of statin intensification on glucose homeostasis and cognitive function in T2D.

Materials and Methods

T2D patients who were taking simvastatin ≤20 mg/day were randomized to continue taking the same dosage of simvastatin (low-dose simvastatin group; LS, n=63) for 12 weeks, or to change to atorvastatin 40 mg/day for 6 weeks, and if tolerated, atorvastatin was increased to 80 mg/day for 6 weeks (high-dose atorvastatin group; HS, n=62). Fasting plasma glucose (FPG), glycated hemoglobin (HbA_1c), plasma insulin, homeostatic model assessment of insulin resistance (HOMA-IR) and of β-cell function (HOMA-B), cognitive functions using Montreal Cognitive Assessment (MoCA), and Trail Making Test (TMT) were assessed at baseline, 6 weeks, and 12 weeks.

Results

Mean age of patients was 58.8±8.9 years, and 72% were female. Mean baseline FPG and HbA_1c were 124.0±27.5 mg/dl and 6.9±0.8%, respectively. No differences in baseline characteristics between groups were observed. Change in HbA_1c from baseline in the LS and HS groups was −0.1% and +0.1% (p=0.03) at 6 weeks, and −0.1% and +0.1% (p=0.07) at 12 weeks. There were no significant differences in FPG, fasting plasma insulin, HOMA-B, HOMA-IR, MoCA score, or TMT between groups at 6 or 12 weeks.

Conclusion

Switching from low-dose simvastatin to high-dose atorvastatin in T2D resulted in a slight increase in HbA_1c (0.1%) without causing cognitive decline.

Keywords:

• high-intensity statin
• glucose homeostasis
• cognitive function
• type 2 diabetes
• T2D

Abbreviations

ANOVA, analysis of variance; CI, confidence interval; COA, certificate of approval; DPP4, dipeptidyl peptidase 4; F/U, follow-up; FDA, Food and Drug Administration; FPG, fasting plasma glucose; GLP-1, glucagon-like peptide 1; HbA_1c, glycated hemoglobin; HDL-C, high-density lipoprotein cholesterol; HMGCR, 3-hydroxy-3-methylglutaryl-CoA reductase; HOMA, homeostatic model assessment; HOMA-B, homeostatic model assessment of β-cell function; HOMA-IR, homeostatic model assessment of insulin resistance; HS, high-dose atorvastatin group; LDL-C, low-density lipoprotein cholesterol; LS, low-dose simvastatin group; MoCA, Montreal Cognitive Assessment; PCSK9, proprotein convertase subtilisin-kexin type 9; SGLT2, sodium glucose cotransporter 2; T2D, type 2 diabetes; TCTR, Thai Clinical Trials Registry; TMT, Trail Making Test, part B.

Data Sharing Statement

The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Ethics Approval and Consent to Participate

All study patients provided written informed consent to participate in this study. The study protocol was approved by the Siriraj Institutional Review Board (SIRB) of the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand (COA no. SI 680/2014).

Disclosure

All authors declare no personal or professional conflicts of interest relating to any aspect of this study. Nuntakorn Thongtang reports grants from Investigator-initiated research grant from Pfizer, during the conduct of the study. The authors report no other potential conflicts of interest for this work.

Additional information

Funding

This study was partially funded by a Siriraj Research Grant from the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand (grant no. R015936001), and partially funded by an investigator-initiated grant from Pfizer. Neither of the aforementioned funders influenced our interpretation of the data, the final conclusions drawn, the drafting of the report, or the decision to publish.