Treatment with exenatide once weekly or twice daily for 30 weeks is associated with changes in several cardiovascular risk markers

Figures & data

Figure 1 Effects of exenatide on glycosylated hemoglobin, body weight, apolipoproteins, and lipoproteins in the total analysis cohort with an overall normal lipid profile at baseline. Week 30 change data are independent of glycemic improvement and weight loss. (A) Glycosylated hemoglobin. (B) Body weight. (C) Apolipoprotein B. (D) Percentage of apolipoprotein B/apolipoprotein A1. (E) Low-density lipoprotein cholesterol and its subclasses. (F) Triglycerides, very low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol. (G) High-density lipoprotein cholesterol and its subclasses. (H) Percentage changes in high-density lipoprotein cholesterol and its subclasses. (Panels A and B) Least squares mean + 95% confidence intervals. *Change from baseline P < 0.0001. (Panels C–G) Adjusted mean + standard error of the mean.

Notes: *Week 30 change from baseline P < 0.05. Once weekly, n = 106, twice daily, n = 105.
Abbreviations: A_1c, glycosylated hemoglobin; ApoB, apolipoprotein B; ApoA1, apolipoprotein A1; BID, twice daily; LDL-C, low-density lipoprotein cholesterol; VLDL-C, very low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; QW, once weekly.

Table 1 Demographics and baseline characteristics for the lipoprotein subclass analysis cohort

	Total cohort
	ExQW n = 106	ExBID n = 105
Age (years)	56 ± 9	55 ± 10
Female (%)	36.8	47.6
Caucasian (%)	84.9	73.3
Black/African American (%)	4.7	11.4
Hispanic (%)	10.4	14.3
Asian (%)	0	1.0
A1c (%)	8.2 ± 0.9	8.2 ± 0.9
Body weight (kg)	101 ± 18	104 ± 22
BMI (kg/m^2)	34.8 ± 5.0	34.9 ± 5.3
Apolipoprotein A (g/L)	1.3 ± 0.2	1.3 ± 0.2
Apolipoprotein B (g/L)	0.81 ± 0.21	0.86 ± 0.23
Apolipoprotein B/A1 (%)	61 ± 15	65 ± 17
Triglycerides (mmol/L)	2.14 ± 1.40	2.11 ± 1.44
LDL-C (mmol/L)	2.16 ± 0.80	2.42 ± 0.94
LDL1-C (mmol/L)	0.22 ± 0.17	0.27 ± 0.19
LDL2-C (mmol/L)	0.17 ± 0.19	0.23 ± 0.28
LDL3-C (mmol/L)	0.75 ± 0.36	0.82 ± 0.43
LDL4-C (mmol/L)	0.54 ± 0.29	0.56 ± 0.29
VLDL-C (mmol/L)	0.59 ± 0.20	0.60 ± 0.21
HDL-C (mmol/L)	1.04 ± 0.24	1.06 ± 0.27
HDL-2 (mmol/L)	0.20 ± 0.09	0.20 ± 0.09
HDL-3 (mmol/L)	0.84 ± 0.16	0.86 ± 0.20
Diabetes medications (%)
None	15.2	10.4
MET alone	34.9	33.3
SFU alone	2.8	6.7
TZD alone	1.9	14.3
MET + TZD	11.3	3.8
MET + SFU	29.2	26.7
TZD + SFU	3.8	2.9
MET + TZD + SFU	0.9	1.9
Dyslipidemia medications (%)
Statin	61.3	44.8
Statin + CAI	7.5	5.7
Niacin	2.8	4.8
Fibrate	7.5	9.5
CAI	8.5	4.8
Fish oil	7.5	5.7

Note: Values are mean ± SD.

Abbreviations: ApoB, apolipoprotein B; ApoA1, apolipoprotein A1; BMI, body mass index; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; VLDL-C, very low-density lipoprotein cholesterol; CAI, cholesterol absorption inhibitor; MET, metformin; SD, standard deviation; SFU, sulfonylurea; TZD, thiazolidinedione; A_1c, glycosylated hemoglobin; ExQW, exenatide once weekly; ExBID, exenatide twice daily.

Table 2 Apolipoprotein and lipoprotein change from baseline in patients with type treated with exenatide for 30 weeks for the lipoprotein subclass analysis cohort

	ExQW (n = 106)	ExBID (n = 105)
ApoA1 (g/L)	0.016 (−0.011, 0.042)	−0.001 (−0.028, 0.025)
ApoB (g/L)	−0.036* (−0.065, −0.008)	−0.013 (−0.041, 0.015)
ApoB/ApoA1 (%)	−3.1 (−5.0, −1.3)*	−1.0 (−2.8, 0.9)
Triglycerides (mmol/L)	−0.361 (−0.566, −0.155)*	−0.339 (−0.546, −0.132)*
LDL-C (mmol/L)	−0.073 (−0.192, 0.028)	0.009 (−0.111, 0.129)
LDL1-C (mmol/L)	−0.008 (−0.035, 0.019)	−0.006 (−0.034, 0.021)
LDL2-C (mmol/L)	0.024 (−0.008, 0.055)	0.012 (−0.019, 0.044)
LDL3-C (mmol/L)	−0.020 (−0.080, 0.040)	0.050 (−0.011, 0.110)
LDL4-C (mmol/L)	−0.052 (−0.098, −0.006)*	−0.015 (−0.061, 0.031)
IDL-C (mmol/L)	−0.005 (−0.025, 0.015)	−0.005 (−0.025, 0.015)
VLDL-C (mmol/L)	−0.327 (−0.360, −0.295)*	−0.343 (−0.375, −0.310)*
VLDL3-C (mmol/L)	−0.007 (−0.022, 0.008)	0.004 (−0.011, 0.019)
VLDL12-C (mmol/L)	−0.004 (−0.026, 0.018)	−0.007 (−0.029, 0.015)
nonHDL-C (mmol/L)	−0.086 (−0.220, 0.049)	0.015 (−0.120, 0.151)
RLPs (mmol/L)	−0.012 (−0.044 0.020)	−0.001 (−0.034, 0.031)
Lp(a) (mmol/L)	−0.012 (−0.040, 0.016)	−0.023 (−0.051, 0.005)
HDL-C (mmol/L)	0.032 (−0.000, 0.065)	0.005 (−0.027, 0.038)
HDL2-C (mmol/L)	0.013 (0.002, 0.025)*	0.005 (−0.007, 0.017)
HDL3-C (mmol/L)	0.018 (−0.007, 0.043)	−0.002 (−0.027, 0.023)

Notes: Values are adjusted mean (95% CI).

* P < 0.05 versus baseline. Adjusted model included changes from baseline in A_1c and weight as covariates.

Abbreviations: ApoB, apolipoprotein B; ApoA1, apolipoprotein A1; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; VLDL-C, very low-density lipoprotein cholesterol; A_1c, glycosylated hemoglobin; Lp(a), lipoprotein(a); RLPs, remnant lipoproteins; ExQW, exenatide once weekly; ExBID, exenatide twice daily.

Figure 2 Effects of exenatide on apolipoproteins, lipoproteins, and high sensitivity C-reactive protein in the subgroup of patients with abnormal lipid values^1–3 at baseline. (A) Apolipoprotein A1, apolipoprotein B, and the ratio of these apolipoproteins; once weekly, n = 85, n = 9, and n = 22, respectively; twice daily, n = 78, 18, and 29, respectively. (B) Low-density lipoprotein cholesterol and subclass ratios; once weekly, n = 28, 28, and 28, respectively; twice daily, n = 36, 36, and 36, respectively. (C) Triglycerides, very low-density lipoprotein (VLDL) cholesterol, VLDL3 cholesterol, ratio of VLDL cholesterol/VLDL3 cholesterol, and intermediate-density lipoprotein cholesterol; once weekly, n = 55, 18, 77, 106, and 7, respectively; twice daily, n = 52, 20, 75, 104, and 6, respectively. (D) Non-high-density lipoprotein cholesterol and remnant lipoproteins; once weekly, n = 26 and n = 13, respectively; and twice daily, n = 34 and n = 21, respectively. (E) Total high-density lipoprotein cholesterol and its subclasses stratified by gender and overall subclass ratio; once weekly, n = 51, 39, 57, 22, 47, and 95, respectively; twice daily, n = 46, 39, 55, 17, 44, and 96, respectively. (F) High sensitivity C-reactive protein in the total cohort; once weekly, n = 104; twice daily, n = 103.

Notes: High sensitivity C-reactive protein in the subgroup with baseline > 3 mg/L and <10 mg/L; once weekly, n = 41; twice daily, n = 32. Adjusted mean + standard error of the mean. *Week 30 change from baseline P < 0.05.
Abbreviations: BL, baseline; ApoB, apolipoprotein B; ApoA1, apolipoprotein A1; LDL-C, low-density lipoprotein cholesterol; BID, twice daily; HDL-C, high-density lipoprotein cholesterol; VLDL-C, very low-density lipoprotein cholesterol; IDL-C, intermediate-density lipoprotein cholesterol; RLPs, remnant lipoproteins; hsCRP, high sensitivity C-reactive protein; QW, once weekly.

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