Is Atorvastatin Associated with New Onset Diabetes or Deterioration of Glycemic Control? Systematic Review Using Data from 1.9 Million Patients

Table 2

Atorvastatin use and dysregulation of diabetes mellitus.

Study author, year	Design	Study location	Total population (% F)	Total population: age, mean (SD), median (range/IQR)	Comparison groups	DM type	Duration of study	Quantitative results related to atorvastatin
Tam et al., 2010 [19]	Clinical trial	China	80 (NA)	NA, NA	Atorvastatin and placebo	T2DM	6 months	FPG (mmol/L) (vs baseline); Placebo: 7.95 ± 1.99 → 7.56 ± 2.06, ns; Atorvastatin: 7.91 ± 2.10 → 8.03 ± 2.48, ns
								HbA1c (%) [mmol/mol] (vs baseline); Placebo: 8.0 ± 1.1 [64 ± 11] → 8.0 ± 1.2 [64 ± 10], ns; Atorvastatin: 7.8 ± 1.2 [62 ± 10] → 8.2 ± 1.4 [66 ± 8], ns
								Placebo vs atorvastatin: ns
Mandosi et al., 2010 [2]	Clinical trial	Italy	22 (23%)	60.8 (7.1), NA	All atorvastatin 20 mg users	T2DM	8 weeks	From baseline; HbA1c (%) [mmol/mol]: 7.6 ± 1.1 [60 ± 11] → 7.6 ± 0.9 [60 ± 14],; FPG (mmol/L): 8.6 ± 2.2 → 9.1 ± 1.9,
Koh et al., 2010 [9]	Clinical trial	Korea	213 (50%)	NA, NA	Atorvastatin 10 mg, 20 mg, 40 mg, 80 mg, and placebo	T2DM & without diabetes	2 months	HbA1c (%) [mmol/mol]; Placebo: 5.8 ± 0.5 [40 ± 18] → 5.8 ± 0.6 [40 ± 17], ns; 10 mg: 5.8 ± 0.6 [40 ± 17] → 6.0 ± 0.6 [42 ± 17] ( vs baseline); 20 mg: 5.9 ± 0.8 [41 ± 15] → 6.2 ± 0.9 [44 ± 14] ( vs baseline, vs placebo); 40 mg: 6.1 ± 0.8 [43 ± 15] → 6.4 ± 1.0 [46 ± 13] ( vs baseline, vs placebo); 80 mg: 6.1 ± 0.8 [43 ± 15] → 6.4 ± 1.1 [46 ± 11] ( vs baseline, vs placebo)
								Global ANOVA:
Tehrani et al., 2010 [20]	Clinical trial	Sweden	20 (NA)	NA; 44 (39–61)	Atorvastatin 80 mg and placebo	T1DM	2 months	HbA1c (%) [mmol/mol]; Placebo: 7.6 ± 0.9 [60 ± 14] → 7.3 ± 0.8 [56 ± 15]; Atorva 80 mg: 7.5 ± 0.9 [58 ± 14] → 7.8 ± 1.1 [62 ± 11],
								Atorva vs placebo:
Rutter et al., 2011 [21]	Clinical trial	UK	119 (17%)	64 (10); NA	Atorvastatin 80 mg and atorvastatin 10 mg	T2DM	2.1 years	HbA1c (%) [mmol/mol] (vs baseline); Atorva 10 mg vs 80 mg: 0.3 [2.4] (0.1–0.5) [0.4–4.3],
Tehrani et al., 2013 [13]	Clinical trial	Sweden	20 (50%)	NA; 44 (39–61)	Atorvastatin 80 mg and placebo	T1DM	2 months	HbA1c (%) [mmol/mol]; Atorvastatin treatment period: 7.5 ± 0.9 [58 ± 14] → 7.8 ± 1.1 [62 ± 11],; Atorvastatin vs placebo:
Grigoropoulou et al., 2014 [18]	Clinical trial	Greece	79 (61%)	NA; NA (45–75)	Atorvastatin 10 mg and control	T2DM	12 months	HbA1c (%) [mmol/mol], (0 → 3mo → 6mo → 12mo); Atorvastatin: 6.7 ± 0.8 [50 ± 15] → 6.7 ± 0.7 [50 ± 16] → 6.8 ± 0.8 [51 ± 15] → 6.9 ± 0.7 [52 ± 16],; Control: 7.0 ± 0.7 [53 ± 16] → 6.8 ± 0.6 [51 ± 17] → 6.9 ± 0.7 [52 ± 16] → 7.0 ± 0.7 [53 ± 16],; Atorvastatin vs control:
								FPG (mg/dL), (0 → 3mo → 6mo → 12mo); Atorvastatin: 141.2 ± 33.3 → 138.1 ± 27.5 → 136.2 ± 29.8 → 138.3 ± 29.8,; Control: 153.9 ± 50.6 → 142.1 ± 54.3 → 142.7 ± 42.2 → 145.6 ± 35.5,; Atorvastatin vs control:
Thongtang et al., 2011 [23]	Clinical trial	USA	272 (49%)	NA, NA	Atorvastatin 80 mg, rosuvastatin 40 mg	T2DM & without diabetes	6 weeks	HbA1c (%) [mmol/mol]; Mean differences vs baseline: Atorvastatin: +0.1 [22] (−2.6–9.3) [−52–78]
Martin et al., 2011 [24]	Clinical trial	Germany	89 (40%)	30 (NA), NA (18–39)	Atorvastatin 80 mg and placebo	T1DM	18 months	HbA1c (%) [mmol/mol] (baseline → 6mo → 18mo); Atorvastatin vs baseline: 7.8 [62] → 6.6 [49] → 6.8 [51],
								Atorvastatin vs placebo: ns
Simsek et al., 2012 [10]	Clinical trial	Netherlands	263 (54%)	60 (10), NA	Atorvastatin and rosuvastatin	T2DM	24 weeks	HbA1c (%) [mmol/mol] 18w vs baseline: Atorva 80 mg: 7.4 ± 1.0 [57 ± 13] → 7.7 ± 1.3 [61 ± 9],; HbA1c 6w vs baseline: Atorva 20 mg: 7.4 ± 1.0 [57 ± 13] → 7.5 ± 1.1 [58 ± 11], ns
								Mean FPG (mmol/L) 18w vs baseline: Atorva 80 mg: 8.7 ± 2.4 → 9.0 ± 3.0, ns; Mean FPG (mmol/L) 6w vs baseline: Atorva 20 mg: 8.7 ± 2.4 → 9.5 ± 3.0,
Puurunen et al., 2013 [25]	Clinical trial	Finland	28 (100%)	NA; NA (29–50)	Atorvastatin 20 mg and placebo	Without diabetes	6 months	FPG, mmol/L (0 → 3mo → 6mo); Atorva: 5.5 ± 0.3 → 5.5 ± 0.4 → 5.5 ± 0.4,; Placebo: 5.3 ± 0.3 → 5.3 ± 0.3 → 5.0 ± 0.5,; Atorva vs placebo (6mo):
Chu et al., 2008 [17]	Clinical trial	Taiwan	29 (50%)	60.0 (2.2); NA (18–80)	Atorvastatin 10 mg, 20 mg, 40 mg	T2DM	12 weeks	HbA1c (%) [mmol/mol]; 10 mg: 7.6 ± 0.4 [60 ± 19] → 7.4 ± 0.3 [57 ± 20], ns
								20 mg: 8.2 ± 0.3 [66 ± 20] → 8.0 ± 0.3 [64 ± 20], ns
								40 mg: 8.3 ± 0.3 [67 ± 20] → 8.7 ± 0.5 [72 ± 18], ns
Goyal et al., 2014 [27]	Clinical trial	India	43 (37.21%)	NA, NA	Atorvastatin 10 mg and placebo	T2DM	12 weeks	HbA1c, (%) [mmol/mol] (vs baseline); Atorva: 7.6 ± 0.9 [60 ± 14] → 7.6 ± 1.4 [60 ± 8],; Placebo: 7.9 ± 0.9 [63 ± 14] → 7.4 ± 1.8 [57 ± 4],
								FPG (mmol/L) (vs baseline); Atorva: 7.44 ± 1.52 → 7.99 ± 2.18,; Placebo: 8.18 ± 1.86 → 8.16 ± 3.28,
Ogawa et al., 2014 [3]	Clinical trial	Japan	1018 (54.22%)	66.4 (11.1); NA	Atorvastatin 10 mg and rosuvastatin 5 mg	T2DM	12 months	HbA1c (%) [mmol/mol] (0 → 6mo → 12mo); Atorva: 6.4 [46] → 6.5 [48] → 6.5 [48], ns
								Glu (mg/dL) (0 → 6mo → 12mo); Atorva: 118.8 → 126.0 → 122.8,
Sadeghi et al., 2014 [5]	Clinical trial	Iran	140 (55%)	NA, NA	Atorvastatin 40 mg and atorvastatin 20 mg	Without diabetes	3 months	HbA1c (%) [mmol/mol] (0 → 3mo): Atorva 40 mg: 5.5 ± 0.6 [37 ± 17] → 5.9 ± 0.6 [41 ± 17],; Atorva 20 mg: 5.5 ± 0.7 [37 ± 16] → 5.5 ± 0.6 [37 ± 17],; Atorva 40 mg vs 20 mg:
								FPG (mg/dL) (0 → 3mo): Atorva 40 mg: 85.67 ± 13.59 → 99.86 ± 16.22,; Atorva 20 mg: 84.63 ± 26.26 → 85.21 ± 14.19,; Atorva 40 mg vs 20 mg:
Black et al., 2014 [28]	Clinical trial	UK	13 (0%)	61.3 (2.5), NA (35–70)	Atorvastatin 10 mg and fenofibrate 267 mg	T2DM	12 weeks	HbA1c (%) [mmol/mol] (0 → 12w); Atorva 10 mg: 7.0 ± 0.2 [53 ± 21] → 7.1 ± 0.3 [54 ± 20], ns; Fenofibrate 267 mg: 7.1 ± 0.2 [54 ± 21] → 7.0 ± 0.3 [53 ± 20], ns; Atorva10 mg vs fenofibrate 267 mg:
								FPG (mmol/L) (0 → 12w); Atorva 10 mg: 7.6 ± 0.3 → 8.4 ± 0.5, ns; Fenofibrate 267 mg: 8.1 ± 0.5 → 7.7 ± 0.5, ns; Atorva 10 mg vs fenofibrate 267 mg:
Tanaka, 2011 [29]	Study 1: prospective cohort study	Japan	114 (49%)	NA, NA	Study 1: (statin-naïve and other statin users) all switched to atorvastatin 10 mg	T2DM	Study 1: 3 months	HbA1c (%) [mmol/mol]; Study 1 (vs baseline); Statin-naïve: 7.6 ± 1.1 [60 ± 11] → 7.5 ± 0.9 [58 ± 14], ns; Statin users: 7.1 ± 1.1 [54 ± 11] → 7.1 ± 1.0 [54 ± 13], ns
	Study 2: retrospective cohort study				Study 2: all atorvastatin users		Study 2: 3 years	Study 2 (vs baseline); Baseline: 7.8 ± 1.5 [62 ± 7] → 1y: 7.6 ± 1.4 [60 ± 8],  → 2y: 7.4 ± 1.5 [57 ± 7],  → 3y: 7.5 ± 1.5 [58 ± 7],
Yamakawa et al., 2008 [11]	Retrospective cohort study	Japan	279 (54%)	NA, NA	Atorvastatin 10 mg; Pitavastatin 2 mg; Pravastatin 10 mg	T2DM	3 months	HbA1c (%) [mmol/mol]; Atorva: 7.0 ± 1.1 [53 ± 11] → 7.4 ± 1.2 [57 ± 10],
								Glu (mg/dL); Atorva: 147 ± 51 → 176 ± 69, .
Takano et al., 2006 [33]	Retrospective cohort study	Japan	154 (56%)	NA, NA	Atorvastatin 10 mg, pravastatin 10 mg	T2DM	3 months	HbA1c (%) [mmol/mol]; Atorva: 6.8 ± 0.9 [51 ± 14] → 7.2 ± 1.1 [55 ± 11],
								Glu (mg/dL); Atorva: 147 ± 50 → 177 ± 70,
Shinozaki et al., 2012 [30]	Cohort study	Japan	1173 (54%)	NA, NA (65–84)	Atorvastatin and atorvastatin-untreated	T2DM	6 years	HbA1c (%) (vs baseline); Atorvastatin treatment period: 0.06% (−0.08%–0.21%, ); Atorvastatin vs untreated: 1.69 (0.42–6.84)

Variables are expressed as absolute numbers, percentages, mean ± SD, and median (IQR). NA: not available; NS: no significance; DM: diabetes mellitus; T2DM: type 2 diabetes mellitus; T1DM: type 1 diabetes mellitus; FPG: fasting plasma glucose; HbA1c: haemoglobin A1c; Glu: glucose; ANOVA: analysis of variance; Mo: months; W: weeks.