TABLE 2.
Cardiovascular outcomes in patients without T2D.
| Study | Patient no/follow up | Patient history | Comparison | Parameter | Outcome difference (95% CI) |
| Metformin | |||||
| Met-remodel (Mohan et al., 2019) | 68/12 months | LVH, CAD with insulin resistance or prediabetes | Metformin (12 months) vs. placebo | LVEF (%) | −0.21 (−4.30–3.88) |
| LV mass (g) | −4.4 (−7.4 to −1.4) | ||||
| NT-proBNP (pg/mL) | 305 (−273 to 884) | ||||
| Camera (Preiss et al., 2014) | 173/1.5 years | CAD | Metformin (1.5 years) vs. placebo | cIMT progression (mm/year) | 0.007 (−0.006 to 0.020) |
| GIPS-III RCT (Lexis et al., 2014; Hartman et al., 2017) | 379/2 years | STEMI, primary PCI | Metformin (4 months) vs. placebo | LVEF (%) | −1.71 (−3.73 to 0.31) |
| NT-proBNP | No change | ||||
| MACE (HR) | 1.84 (0.68–4.97) | ||||
| MetCAB (El Messaoudi et al., 2015) | 111/24 h | CABG surgery | Metformin (3 days before surgery) vs. placebo | Troponin I (%) | 12.3 (−12.4 to 44.1) |
| Arrhythmia | No change | ||||
| Days in Intensive Care | No change | ||||
| Unit | |||||
| GLP1-RA | |||||
| NCT02001363 (Chen et al., 2015; Huang et al., 2017) | 92/3 months | STEMI, T2D: 20% in liraglutide, 16% in control | Liraglutide, 30 min before PCI, total 7 days | LVEF (WMD, %) | 4.60 (0.84–8.36) |
| MACE* (HR) | 0.52 (0.21–1.27) | ||||
| Infarct size (% LV) | −6.20 (−9.81 to −2.59) | ||||
| NCT02001363 (Chen et al., 2016b; Huang et al., 2017) | 90/3 months | NSTEMI, T2D: 20% in liraglutide, 28% in control | Liraglutide 7 days prior PCI vs. placebo | LVEF (WMD, %) | 5.10 (2.58–7.62) |
| MACE* (HR) | 0.56 (0.20–1.53) | ||||
| Kyhl et al. (Kyhl et al., 2016; Huang et al., 2017) | 334/5.2 years | STEMI 7–11% diabetes | Exenatide i.v. injection | LVEF (WMD, %) | 0.00 (−2.42 to 2.42) |
| MACE* (HR) | 0.89 (0.61–1.28) | ||||
| NCT01254123 (Roos et al., 2016; Huang et al., 2017) | 91/4 months | STEMI | Exenatide 30 min before PCI, followed by 20μg/day for 3 days | LVEF (WMD, %) | −1.20 (−4.74 to 2.34) |
| MACE* (HR) | 1.17 (0.17–7.93) | ||||
| Infarct size (% LV) | −1.80 (−5.79 to 2.19) | ||||
| Live (Jorsal et al., 2017) | 241 total, 167 w/o T2D/24 weeks | HFrEF LVEF ≤ 45% | Liraglutide (24 weeks) vs. placebo | LVEF (%) | −0.80 (−2.1 to 0.5) |
| NT-proBNP (pg/mL) | −140 (−317 to 37) | ||||
| Fight (Margulies et al., 2016) | 300 total, 41% w/o T2D/180 days | HFrEF LVEF ≤ 40%, HHF in last 14 days | Liraglutide (180 days) vs. placebo | CV death (HR) | 1.10 (0.57–2.14) |
| HHF (HR) | 1.30 (0.89–1.88) | ||||
| LVEF (%) | −0.1 (−2.3 to 2.1) | ||||
| SGLT2 inhibitors | |||||
| DAPA-HF (McMurray et al., 2019) | 2,605 w/o T2D of 4,744 total | HFrEF: LVEF ≤ 40%, NYHA class II-IV, NT-proBNP ≥ 600 pg/mL (≥400 pg/mL with prev. HHF) | Dapagliflozin vs. placebo | Prim. outcome# no T2D (HR) | 0.73 (0.60–0.88) |
| Prim. outcome# total (HR) | 0.74 (0.65–0.85) | ||||
| CV death (HR) | 0.82 (0.69–0.98) | ||||
| HHF (HR) | 0.70 (0.59–0.83) | ||||
*MACE defined as death due to all causes, cardiac death, heart failure, re-myocardial infarction, repeated revascularization, and stroke. #Primary outcome: composite of worsening heart failure (hospitalization or an urgent visit resulting in intravenous therapy for heart failure) or cardiovascular death. CAD, coronary artery disease, including previous myocardial infarction/unstable angina and/or previous revascularization by either percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery; CI, confidence interval; cIMT, carotid intima-media thickness; HFrEF, heart failure with reduced ejection fraction; HHF, hospitalization for heart failure; HR, hazard rate; LV, left ventricular; LVEF, left ventricular ejection fraction; LVH, left ventricular hypertrophy; MACE, major adverse cardiovascular events; NSTEMI, non-ST-elevation myocardial infarction; NT-proBNP, N-terminal pro-brain natriuretic peptide; NYHA, New York Heart Association; STEMI, ST-elevation myocardial infarction; WMD, weighted mean difference.