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

Figures & data

Figure 1 Flow diagram of patient enrollment and group allocation.

Table 1 Baseline Demographic and Clinical Characteristics of Study Patients

Parameters	Low-Dose Simvastatin (n=63)	High-Dose Atorvastatin (n=62)	p-value
Age (years)	58.2±9.5	58.4±8.9	0.91
Female gender (n,%)	48 (76.2%)	42 (67.7%)	0.29
Body weight (kg)	68.3±11.7	65.6±13.7	0.25
Body mass index (kg/m^2)	28.0±4.3	26.9±4.2	0.15
Waist circumference (cm)	93.2±12.5	91.9±10.3	0.50
Duration of diabetes (months)	84 (42–144)	96 (48–180)	0.19
Systolic blood pressure (mmHg)	132.2±17.3	130.2±18.1	0.54
Diastolic blood pressure (mmHg)	72.7±10.2	72.9±9.3	0.88
Hypertension	46 (73.0%)	47 (75.8%)	0.72
Chronic kidney disease	5 (7.9%)	2 (3.2%)	0.44
Microvascular complication
Nephropathy Retinopathy Peripheral neuropathy	11 (17.5%) 7 (11.1%) 4 (6.3%)	11 (17.7%) 11 (17.7%) 5 (8.1%)	0.51 0.44 0.74
Education
None Primary school Junior high school High school Bachelor Doctorate	3 (4.8%) 20 (31.7%) 13 (20.6%) 9 (14.3%) 15 (23.8%) 3 (4.8%)	3 (4.8%) 16 (25.8%) 6 (9.7%) 15 (24.2%) 18 (29.0%) 4 (6.5%)	0.42
MoCA, Thai	20.8±4.0	21.0±3.8	0.80
Trail Making Test, part B (second)	122.0 (80.8–301.0)	110.0 (72.5–301.0)	0.84
Simvastatin dosage (mg/day)	15.1±5.1	14.8±5.2	0.73
Cholesterol (mg/dl)	147.8±19.5	147.3±18.6	0.86
Triglyceride (mg/dl)	113.0 (82.0–168.0)	98.0 (71.0–133.0)	0.06
HDL-C (mg/dl)	55.2±13.6	53.5±13.3	0.49
Calculated LDL-C (mg/dl)	67.4±14.1	72.7±13.2	0.03
Fasting plasma glucose (mg/dl)	121.5±21.6	126.5±32.3	0.30
HbA1c (%)	6.9±0.8	6.9±0.9	0.75
Insulin (µU/mL)	11.7 (7.9–17.9)	10.7 (6.8–16.2)	0.36
HOMA-B (%)	73.1 (54.8–100.2)	62.7 (46.9–100.0)	0.36
HOMA-IR	1.6 (1.1–2.5)	1.5 (1.0–2.3)	0.34

Note: Data presented as mean ± standard deviation (SD) or median (interquartile range), number and percentage.

Abbreviations: MoCA, Montreal Cognitive Assessment test; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; HbA_1c, glycated hemoglobin; HOMA-B, homeostatic model assessment of beta call function; HOMA-IR, homeostatic model assessment of insulin resistance.

Table 2 Hypoglycemic Agents Used Compared Between the Two Study Groups

Hypoglycemic Agent	Low-Dose Simvastatin (n=63), n (%)	High-Dose Atorvastatin (n=62), n (%)	p-value
Metformin	61 (96.8%)	60 (96.8%)	1.00
Sulfonylurea	38 (60.3%)	31 (50.0%)	0.24
Glinide	0 (0.0%)	1 (1.6%)	0.50
Pioglitazone	14 (22.2%)	14 (22.6%)	0.96
Alpha-glucosidase inhibitor	3 (4.8%)	5 (8.1%)	0.49
DPP-4 inhibitor (n, %)	4 (6.3%)	7 (11.3%)	0.15
GLP-1 receptor agonist	1 (1.6%)	0 (0.0%)	1.00
SGLT2-inhibitor	0 (0.0%)	1 (1.6%)	0.50
Insulin analogue	5 (7.9%)	8 (12.9%)	0.53

Abbreviations: DPP4, dipeptidyl peptidase 4; GLP-1, glucagon like peptide 1; SGLT2, sodium glucose cotransporter 2.

Table 3 Anthropometric, Glycemic, and Lipid Parameters at 6 and 12 Weeks

Parameters	6 Weeks			12 Weeks
	Low-Dose Simvastatin (n=63)	High-Dose Atorvastatin (n=62)	p	Low-Dose Simvastatin (n=63)	High-Dose Atorvastatin (n=62)	p
Body weight (kg)	68.3±11.9	65.7±13.8	0.28	67.8±11.7	65.5±13.9	0.33
Waist circumference (cm)	93.7±11.3	92.3±10.0	0.45	93.1±10.9	92.5±11.5	0.76
Systolic blood pressure (mmHg)	131.1±16.9	132.8±17.7	0.59	132.6±14.6	127.2±18.5	0.07
Diastolic blood pressure (mmHg)	74.1±11.3	73.2±10.5	0.67	73.9±10.2	72.1±10.7	0.34
FPG (mg/dl)	125.3±24.2	129.3±33.6	0.45	123.6±29.1	128.0±31.9	0.42
HbA1c (%)	6.8±0.8	6.9±0.9	0.60	6.9±0.8	7.0±0.8	0.69
Insulin (µU/mL)	11.7 (8.4–18.0)	10.6 (7.4–16.1)	0.42	11.8 (7.4–18.7)	11.5 (6.9–16.5)	0.68
HOMA-B (%)	65.6 (53.0–100.7)	66.0 (45.7–99.6)	0.54	64.6 (52.4–97.2)	70.4 (47.0–97.2)	0.87
HOMA-IR	1.7 (1.1–2.5)	1.5 (1.1–2.4)	0.42	1.7 (1.0–2.6)	1.6 (1.0–2.3)	0.60
Cholesterol (mg/dl)	148.0±24.5	128.4±24.6	<0.01	152.1±23.7	125.8±31.7	<0.01
Triglyceride (mg/dl)	115.0 (82.0–152.0)	86.5 (63.0–111.0)	<0.01	114.0 (80.0–147.0)	84.0 (68.0–105.0)	<0.01
HDL-C (mg/dl)	54.8±12.1	51.8±13.4	0.19	55.1±13.4	51.4±14.1	0.14
Calculated LDL-C (mg/dl)	67.7±19.0	56.8±15.4	<0.01	73.1±20.1	55.4±26.4	<0.01

Abbreviations: FPG, fasting plasma glucose; HbA_1c, glycated hemoglobin; HOMA-B, homeostatic model assessment of beta call function; HOMA-IR, homeostatic model assessment of insulin resistance; HDL-C, high-density lipoprotein cholesterol; Calculated LDL-C, calculated low-density lipoprotein cholesterol.

Figure 2 Changes from baseline to 6 and 12 weeks for (A) fasting plasma glucose (FPG); (B) glycated hemoglobin (HbA_1c); (C) homeostatic model assessment of beta call function (HOMA-B); and, (D) HOMA of insulin resistance (HOMA-IR) compared between groups.

Table 4 Neurocognition Testing Scores of Study Patients. Mean Montreal Cognitive Assessment (MoCA) Score and Median Trail Making Test, Part B (TMT) Score in Seconds Compared Between Groups at All Study Time Points

Groups	Mean MoCA Score			Median TMT (Seconds)
	Baseline	6 Weeks	12 Weeks	Baseline	6 Weeks	12 Weeks
Low-dose simvastatin	20.8±4.0	22.5±4.2	23.7±4.5	123.0 (70.8–301.0)	116.5 (70.0–188.5)	105.5 (69.5–222.0)
High-dose atorvastatin	21.0±3.8	22.8±3.9	24.1±3.9	110.0 (72.5–301.0)	100.0 (72.0–301.0)	100.0 (65.0–301.0)
p-value*	0.80	0.70	0.57	0.84	0.78	0.85

Note: *p-value reflects the difference between the LS and HS groups.

Table 5 Neurocognition Testing Scores of Study Patients. Mean Change in MoCA Score and Median TMT Score in Seconds from Baseline to 6 and 12 Weeks Compared Between Groups

Groups	Mean Change in MoCA Score from Baseline		Median Change in TMT from Baseline (Seconds)
	6 Weeks	12 Weeks	6 Weeks	12 Weeks
Low-dose simvastatin	+1.7±2.5	+2.8±2.5	−6.5 (−49.0 to +7.2)	−14.5 (−45.8 to +0.3)
High-dose atorvastatin	+1.8±3.2	+3.1±3.0	0.0 (−21.0 to 0.0)	0.0 (−34.5 to +5.0)
p-value*	0.83	0.62	0.57	0.29

Note: *p-value reflects the difference in change from baseline between the LS and HS groups.