Table 2.
Studies assessing the association between lipid-lowering drugs and disorders of glucose metabolism.
| Author, Year | N | Characteristics/Therapy | Mean Follow-Up | Mean Results | Statistical Measures (OR, HR or RR) (95% CI) |
|---|---|---|---|---|---|
| Sattar, 2010 [76] | 91,140 | Meta-analysis. All statins | 4 years | NODM 9% | OR 1.09 (1.02–1.17) |
| Waters, 2013 [77] | 15,056 | Atorvastatin 80 mg vs. atorvastatin 10 mg or simvastatin 20–40 mg | 4.9 years | 0–1 NODM risk factors: NODM 3.22% vs. 3.35% 2–4 NODM risk factors: NODM 14.3% vs. 11.9% |
HR 0.97 (0.77–1.22) HR 1.24 (1.08–1.42) |
| Cederberg, 2014 [78] | 8749 | Non-diabetic patients. All statins vs. control | 5.9 years | NODM 11.2% vs. 5.8% High and low dose simvastatin High dose atorvastatin |
HR 1.46 (1.22–1.74) HR 1.44 (1.23–1.68) and 1.28 (1.01–1.62) HR 1.37 (1.14–1.65) |
| Khan, 2019 [79] | 163,688 | Non-diabetic patients. Intensive therapy (PCSK9i or statins) vs. less intensive therapy (placebo/usual care) |
4.2 years | NODM 6.1% vs. 5.8% | RR 1.07 (1.03–1.11) |
| Ko, 2019 [80] | 2,162,119 | Duration of statin use (<1 year vs. 1–2 years vs. >2 years) Cumulative dosing of statin (low-tertile vs. middle-tertile vs. high-tertile) |
3.9 years | NODM 8.2% vs. 14.6% vs. 19.8% NODM 6.7% vs. 11.5% vs. 18.6% |
HR 1.25 (1.21–1.28) vs. 2.22 (2.16–2.29) vs. 2.62 (2.56–2.67) HR 1.06 (1.02–1.10) vs. 1.74 (1.70–1.79) vs. 2.52 (2.47–2.57) |
| Choi, 2018 [81] | 2483 | 5–10 mg rosuvastatin vs. 10–20 mg and atorvastatin vs. 2–4 mg pitavastatin | 3 years | NODM 10.4% vs. 8.4% vs. 3% | HR Rosuvastatin vs. Pitavastatin: 3.9 (1.8–8.7) HR Atorvastatin vs. Pitavastatin: 2.6 (1.2–5.9) |
| Freeman, 2001 [82] | 5974 | All statins | 3.5–6.1 years | NODM 2.3% | Pravastatin therapy HR 0.70 (0.50–0.99) |
| Hiramitsu, 2010 [83] | 120 | Ezetimibe | 12 weeks | HbA1c: −3.4%; p = 0.05 | |
| Dagli, 2007 [84] | 100 | High-dose pravastatin (40 mg) vs. combination low-dose pravastatin (10 mg) plus ezetimibe (10 mg) | 6 months | HOMA IR: 3.16 vs. 2.05; p = 0.01 | |
| Her, 2010 [85] | 76 | Atorvastatin 20 mg vs. rosuvastatin 10 mg vs. atorvastatin 5 mg plus ezetimibe 5 mg | 8 weeks | HbA1c: +3% vs. +1.2% vs. −0.4%; p = 0.03 | |
| Takeshita, 2013 [86] | 32 | Ezetimibe vs. placebo in NAFLD patients | 6 months | HbA1c: 6.5% vs. 6%; p = 0.041 | |
| Sabatine, 2017 [87] | 27,564 | EVOLOCUMAB vs. placebo | 2.2 years | NODM 8% vs. 7.6% | HR 1.05 (0.94–1.17) |
| de Carvalho, 2017 [88] | 68,123 | Meta-analysis: PCSK9i vs. placebo | 78 weeks | Mean difference in FBG 1.88 (0.91–2.68) mg/dL; p < 0.001 HbA1c 0.032% (0.011–0.050); p <0.001 NODM |
RR 1.04 (0.96–1.13); p = 0.427 |
| Chen, 2019 [89] | 65,957 | Meta-analysis: PCSK9i vs. placebo | Global NODM ALIROCUMAB Homogeneous statin use ALIROCUMAB and EVOLOCUMAB vs. ezetimibe |
RR 0.97 (0.91–1.02) RR 0.91 (0.85–0.98) RR 2.14 (1.12–4.07) RR 0.60 (0.37–0.99) |
|
| Leiter, 2022 [90] | 3621 | Bempedoic acid vs. placebo | 1 year | NODM 0.3% vs. 0.8%; p > 0.05 T2DM: HbA1c −0.12% vs. 0.07%; p < 0.0001 pre-T2DM: HbA1c −0.06% vs. −0.02; p < 0.0004 |
|
| Masson, 2020 [91] | 3629 | Meta-analysis: bempedoic acid vs. placebo | 4–52 weeks | NODM | OR 0.66 (0.48–0.90) |
| Handelsma, 2010 [92] | 216 | Colesevelam vs. placebo in pre-T2DM patients |
16 weeks | FBG: −4.0 mg/dL vs. −2.0 mg/dL; p = 0.02 HbA1c: −0.12% vs. −0.03%; p = 0.02 |
OR: odd ratio; HR: hazard ratio; RR: risk ratio; CI: confidence interval; NODM: new-onset diabetes mellitus; HbA1c: glycosylated hemoglobin; HOMA-IR: insulin-resistance index; NAFLD: non-alcoholic fatty liver disease; PCSK9i: PCSK9 inhibitors; FBG: fasting blood glucose; T2DM: type 2 diabetes.