Extended-release niacin/laropiprant significantly improves lipid levels in type 2 diabetes mellitus irrespective of baseline glycemic control

Figures & data

Table 1 Demographic and baseline characteristics of study population by HbA_1c subgroups

Parameter	HbA1c ≤6.8%		HbA1c >6.8%
	ERN/LRPT (N=217)	Placebo (N=175)	ERN/LRPT (N=215)	Placebo (N=161)
Age, years	62.59±9.15	61.61±9.41	61.47±9.29	62.32±9.37
Sex, male, n (%)	134 (61.8)	115 (65.7)	122 (56.7)	99 (61.5)
BMI, kg/m^2	30.72±6.07	30.62±5.82	31.61±6.94	30.39±5.84
Race, n (%)
White	175 (80.6)	145 (82.9)	184 (85.6)	137 (85.1)
Asian	28 (12.9)	19 (10.9)	22 (10.2)	17 (10.6)
Other	14 (6.5)	11 (6.3)	9 (4.2)	7 (4.3)
HbA1c, %	6.32±0.33	6.34±0.36	7.49±0.48	7.50±0.43
FPG, mg/dL	117.4±21.58	120.6±23.15	146.1±36.12	147.3±34.96
Prior antihyperglycemic therapy, n (%)	214 (98.6)	173 (98.9)	213 (99.1)	160 (99.4)
Prior lipid-modifying therapy, n (%)	177 (81.6)	147 (84.0)	177 (82.3)	131 (81.4)
LDL-C, mg/dL	85.65±21.14	85.50±16.58	88.40±19.67	85.02±19.41
HDL-C, mg/dL	51.07±14.85	50.69±13.86	48.73±12.00	49.84±12.62
TG,a mg/dL	121.0	128.0	129.0	129.0
TC, mg/dL	163.9±25.59	162.7±23.06	167.0±26.31	163.2±26.51
Non–HDL-C, mg/dL	112.8±24.59	112.0±20.36	118.3±23.99	113.4±24.09
Apo B, mg/dL	90.86±17.80	90.32±15.70	95.18±19.74	92.35±17.48
Apo A-I, mg/dL	153.8±28.63	153.4±28.73	152.2±24.74	153.7±26.38
Lp(a),a mg/dL	10.00	11.00	8.50	10.00
hs-CRP,a mg/dL	1.65	1.40	1.90	1.50

Notes: All values are mean ± SD except where noted.

a Median value, SD not calculated.

Abbreviations: Apo, apolipoprotein; BMI, body mass index; ERN/LRPT, extended-release niacin/laropiprant; FPG, fasting plasma glucose; HbA_1c, glycosylated hemoglobin; HDL-C, high-density lipoprotein cholesterol; hs-CRP, high-sensitivity C-reactive protein; LDL-C, low-density lipoprotein cholesterol; Lp, lipoprotein; SD, standard deviation; TC, total cholesterol; TG, triglycerides.

Table 2 Demographic and baseline characteristics of study population by FPG subgroups

Parameter	FPG ≤129 mg/dL		FPG >129 mg/dL
	ERN/LRPT (N=225)	Placebo (N=163)	ERN/LRPT (N=207)	Placebo (N=173)
Age, years	62.04±9.66	61.83±9.44	62.02±8.76	62.06±9.36
Sex, male, n (%)	130 (57.8)	101 (6.20)	126 (60.9)	113 (65.3)
BMI, kg/m^2	31.11±6.63	30.26±5.81	31.22±6.43	30.74±5.84
Race, n (%)
White	179 (79.6)	124 (76.1)	180 (8.70)	158 (91.3)
Asian	27 (12.0)	25 (15.3)	23 (11.1)	11 (6.4)
Other	19 (8.4)	14 (8.6)	4 (1.9)	4 (2.3)
HbA1c, %	6.60±0.60	6.57±0.62	7.24±0.68	7.20±0.64
FPG, mg/dL	107.4±14.89	108.0±13.71	158.0±26.38	157.3±25.81
Prior antihyperglycemic therapy, n (%)	222 (98.7)	160 (98.2)	205 (99.0)	173 (100)
Prior lipid-modifying therapy, n (%)	181 (80.4)	140 (85.9)	173 (83.6)	138 (79.8)
LDL-C, mg/dL	86.12±21.43	84.37±18.07	87.99±19.31	86.11±17.88
HDL-C, mg/dL	49.80±14.06	50.90±13.13	50.01±12.99	49.71±13.41
TG,a mg/dL	121.0	118.0	129.0	135.0
TC, mg/dL	163.2±26.72	160.8±24.85	167.9±24.97	165.0±24.53
Non–HDL-C, mg/dL	113.4±24.31	109.9±21.17	117.9±24.38	115.3±22.87
Apo B, mg/dL	90.79±18.48	89.01±16.43	95.42±19.09	93.45±16.49
Apo A-I, mg/dL	151.7±28.21	154.1±27.17	154.5±25.05	153.0±28.05
Lp(a),a mg/dL	10.00	12.00	8.00	9.00
hs-CRP,a mg/dL	1.70	1.30	2.00	1.55

Notes: All values are mean ± SD except where noted.

a Median value, SD not calculated.

Abbreviations: Apo, apolipoprotein; BMI, body mass index; ERN/LRPT, extended-release niacin/laropiprant; FPG, fasting plasma glucose; HbA_1c, glycosylated hemoglobin; HDL-C, high-density lipoprotein cholesterol; hs-CRP, high-sensitivity C-reactive protein; LDL-C, low-density lipoprotein cholesterol; Lp, lipoprotein; SD, standard deviation; TC, total cholesterol; TG, triglycerides.

Table 3 Between-group differences (95% CI) in LS mean percentage changes from baseline in plasma lipids and proteins at Week 12 (extended-release niacin/laropiprant–placebo)

Parameter	HbA1c≤6.8%	HbA1c>6.8%	Treatment × subgroup interaction P-value	FPG ≤129 mg/dL	FPG >129 mg/dL	Treatment × subgroup interaction P-value
LDL-C, mg/dL	−15.6 (−20.5, −10.7)c	−19.1 (−24.3, −23.9)c	0.350	−15.9 (−21.0, −10.8)c	−18.6 (−23.6, −13.7)c	0.470
HDL-C, mg/dL	22.5 (19.0, 26.0)c	22.8 (19.0, 26.6)c	0.820	24.8 (21.3, 28.2)c	20.2 (16.3, 24.1)c	0.089
TG,a mg/dL	−23.0 (−28.7, −17.0)c	−23.2 (−29.3, −16.9)c	0.766	−24.4 (−30.5, −18.0)c	−22.0 (−27.8, −16.2)c	0.708
TC, mg/dL	−4.7 (−7.4, −1.9)c	−7.6 (−10.9, −4.3)c	0.203	−5.0 (−8.1, −2.0)c	−7.1 (−10.1, −4.0)c	0.378
Non–HDL-C, mg/dL	−17.4 (−21.4, −13.4)c	−20.6 (−25.4, −15.8)c	0.359	−17.8 (−22.1, −13.5)c	−19.6 (−24.1, −15.1)c	0.648
Apo B, mg/dL	−16.9 (−20.5, −13.2)c	−17.3 (−21.1, −13.6)c	0.874	−16.2 (−19.9, −12.6)c	−17.7 (−21.5, −13.9)c	0.628
Apo A-I, mg/dL	9.1 (6.2, 12.0)c	7.4 (4.9, 10.0)c	0.441	10.2 (7.4, 12.9)c	6.2 (3.4, 9.0)c	0.052
Lp(a),a mg/dL	−26.3 (−33.1, −20.1)c	−22.5 (−28.6, −16.0)c	0.202	−23.3 (−29.0, −16.7)c	−25.0 (−31.6, −20.0)c	0.424
hs-CRP,a mg/dL	−18.0 (−33.3, −5.7)b	−16.3 (−35.0, −9.8)	0.525	−16.7 (−31.6, −5.1)b	−18.0 (−37.5, −11.1)b	0.147

Notes: All values are expressed as mean (95% CI) except where noted.

a Median (95% CI). Significant difference between treatments:

b P<0.05;

c P<0.001.

Abbreviations: Apo, apolipoprotein; CI, confidence interval; FPG, fasting plasma glucose; HbA_1c, glycosylated hemoglobin; HDL-C, high-density lipoprotein cholesterol; hs-CRP, high-sensitivity C-reactive protein; LDL-C, low-density lipoprotein cholesterol; Lp, lipoprotein; LS, least squares; TC, total cholesterol; TG, triglycerides.

Table 4 Summary of selected safety parameters at Week 36

Parameter	HbA1c ≤6.8%		HbA1c >6.8%		FPG ≤129 mg/dL		FPG >129 mg/dL
	ERN/LRPT	Placebo	ERN/LRPT	Placebo	ERN/LRPT	Placebo	ERN/LRPT	Placebo
Worsening of diabetesa	22 (10.1)	13 (7.4)	67 (31.2)	23 (14.3)	28 (12.4)	10 (6.1)	61 (29.5)	26 (15.0)
Intensification of antihyperglycemic medication	17 (7.8)	8 (4.6)	62 (28.8)	20 (12.4)	22 (9.8)	7 (4.3)	57 (27.5)	21 (12.1)
Hepatitis-related adverse eventb	0 (0.0)	0 (0.0)	0 (0.0)	1 (0.06)	0 (0.0)	1 (0.6)	0 (0.0)	0 (0.0)
ALT/AST consecutive elevations ≥3× ULN	2 (0.9)	1 (0.6)	1 (0.5)	0 (0.0)	3 (1.3)	0 (0.0)	0 (0.0)	1 (0.6)
Confirmed adjudicated cardiovascular events	0 (0.0)	3 (1.7)	1 (0.5)	1 (0.6)	0 (0.0)	2 (1.2)	1 (0.5)	2 (1.2)
CK elevations ≥10× ULN	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
CK elevations ≥10× ULN with muscle symptoms	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)

Notes: Data are shown as number (%) of patients.

a Defined as experiencing an investigator-reported diabetes-related adverse experience and/or requiring intensification of antidiabetes medication;

b based on investigator report.

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; CK, creatine kinase; ERN/LRPT, extended-release niacin/laropiprant; FPG, fasting plasma glucose; HbA_1c, glycosylated hemoglobin; ULN, upper limit of normal.

Table 5 Summary of mean change ± standard deviation from baseline in glucose-related parameters at Week 36

Parameter	HbA1c ≤6.8%		HbA1c >6.8%		FPG ≤129 mg/dL		FPG >129 mg/dL
	ERN/LRPT	Placebo	ERN/LRPT	Placebo	ERN/LRPT	Placebo	ERN/LRPT	Placebo
HbA1c, % (n)	0.45±0.74 (157)	0.30±0.43 (142)	0.30±0.74 (155)	0.05±0.60 (139)	0.42±0.76 (175)	0.20±0.46 (137)	0.31±0.72 (137)	0.16±0.60 (144)
FPG, mg/dL, (n)	14.47±36.18 (150)	4.85±21.62 (140)	12.72±47.47 (144)	2.22±42.05 (128)	24.59±39.07 (163)	11.85±24.33 (130)	−0.05±41.70 (131)	−4.18±37.86 (138)

Abbreviations: ERN/LRPT, extended-release niacin/laropiprant; FPG, fasting plasma glucose; HbA_1c, glycosylated hemoglobin; n, number of patients in the subgroup.