Table 3.
Comparative table of clinical trials and studies, investigating the safety of treatment with gliptins and glitazones
| Author | Treatment | Change in mean body weight |
|---|---|---|
| Bolli et al., 2009 [31] | VIL + MET | ↑ 0.2 kg, non-significant |
| PIO + MET | ↑ 2.6 kg, P < 0.001 | |
| Jindal et al., 2015 [1] | VIL + MET | No change in body weight |
| PIO + MET | ↑1.2 ± 0.5 kg | |
| Chawla et al., 2013 [25] | SIT + MET | ↓ 0.58 kg, statistically significant |
| PIO + MET | ↑0.90 kg, statistically significant | |
| Russell-Jones et al., 2012 [18] | EQW | ↓ 2.0 kg |
| MET | ↓ 2.0 kg (P = 0.892 vs. EQW) | |
| PIO | ↑ 1.5 kg (P < 0.001 vs. EQW) | |
| SIT | ↓ 0.8 kg (P < 0.001 vs. EQW) | |
| Rosenstock et al., 2007 [19] | VIL | ↑ 0.2 ± 0.3 kg |
| PIO | ↑ 1.5 ± 0.3 kg | |
| VIL + PIO (50/15 mg) | ↑ 1.4 ± 0.3 kg | |
| ↑ 2.1 ± 0.3 kg | ||
| VIL + PIO (100/30 mg) | ||
| Risk of fractures | ||
| Bone et al., 2013 [50] | PIO | BMD of total proximal femur (primary and point): |
| PLB | Least squares mean from baseline: −0.69 % PIO, −0.14 % PLB (P = 0.170) statistically non-significant | |
| Bone remodeling markers: | ||
| statistically non-significant between-group differences | ||
| Bazelier et al., 2012 [46] | Biguanide or Sulfonyluerum | ↓ risk HR = 1.15, 95 % CI 1.13–1.18 |
| Biguanide and Sulfonyluerum | ↓ risk HR = 1.00, 95 % CI 0.96–1.04 | |
| TZDs | ↑ risk HR = 1.27, 95 % CI 1.06–1.52 | |
| Insulin | ↑ risk HR = 1.25, 95 % CI 1.20–1.31 | |
| Glintborg et al., 2008 [47] | PIO | ↓BMD [geometric means (−2 to +2SD): lumbar spine 1.140 (0.964–1.348) vs. 1.127 (0.948–1.341)g/cm2 (average decline 1.1 %) and femoral neck 0.966 (0.767–1.217) vs. 0.952 (0.760–1.192)g/cm2 (average decline 1.4 %), both p < 0.05] |
| PLB | ||
| Meier et al., 2008 [48] | PIO | ↑ hip and nonvertebral osteoporotic fractures OR = 2.59, 95 % CI 0.96–7.01 |
| ROSI | ↑ hip and nonvertebral osteoporotic fractures OR = 2.38, 95 % CI 1.39–4.09 | |
| Colhoun et al., 2012 [49] | PIO | ↑hip fractures risk OR = 1.18, 95 % CI 1.00–1.40 |
| ROSI | ↑hip fractures risk OR = 1.16, 95 % CI 1.06–1.26 | |
| Bunck et al., 2012 [53] | VIL | Bone resorption marker: S-CTx (cross-linked C-terminal telopeptide): between-group ratio 1.15 ± 0.17, P = 0.320 serum alkaline phosphatase, calcium and phosphate - unaffected |
| PLB | ||
| Monami et al., 2011 [52] | DPP-4 | ↑ risk of bone fractures Mantel Haenszel odds ratio [MH-OR] 0.60, 95 % CI 0.37–0.99, P = 0.045 |
| PLB, other treatments | ||
| Risk of cardiovascular complications | ||
| Dormandy et al., 2005 [55] | PIO | ↓ all-cause mortality, non-fatal myocardial infarction, and stroke (main secondary endpoint) |
| ↑ HF (11 % vs. 8 %, p < 0.0001) | ||
| PLB | ||
| Wilcox et al., 2007 [56] | PIO | ↓ fatal or nonfatal stroke (HR = 0.53, 95 % CIs = 0.34–0.85; P = 0.0085) |
| ↓ cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (HR = 0.72, 95 % CIs = 0.53–1.00; P = 0.0467) | ||
| PLB | ||
| Nissen et al., 2007 [57] | ROSI | ↑ myocardial infarction (OR = 1.43, 95 % CI, 1.03–1.98; P = 0.03) |
| ↑ death from cardiovascular causes (OR = 1.64, 95 % CI, 0.98–2.74; P = 0.06) | ||
| Control group | ||
| Lincoff et al., 2007 [59] | PIO | ↓ death, myocardial infarction, or stroke (OR = 1.43, 95 % CI, 1.03–1.98; P = 0.03) |
| ↑ HF (НR, 1.41; 95 % CI, 1.14–1.76; P = 0.002) | ||
| Control group | ||
| Gallagher et al., 2011 [63] | PIO | |
| ROSI | ↑ death (RR 1.20; 95 % CI 1.08–1.34) | |
| ↑ HF (RR 1.73; 95 % CI 1.19–2.51) | ||
| Breunig et al., 2014 [62] | PIO | |
| ROSI | ↑ HF (HR = 1,79, 95 % CI = 1.16–2.76, P = 0.009) | |
| MET | ||
| Seong et al., 2015 [61] | PIO + MET | ↓risk of CVD 0.89 (95 % CI, 0.81–0.99) |
| ↓risk of IS 0.81 (95 % CI, 0.67–0.99) | ||
| ↑risk of HF 4.81 (95 % CI, 3.53–6.56) | ||
| DPP-4i + MET | ||
| Scirica et al., 2013 [65] | SAXA | ↑ HF (HR 1.27; 95 % CI, 1.07–1.51; P = 0.007) |
| Scirica et al., 2014 [66] | PLB | |
| Monami et al., 2014 [67] | DPP-4 inhibitors | ↑ HF (MH-OR: 1.19[1.03; 1.37]; p = 0.015). |
| Control group | ||
| Clifton P, 2014 [68] | DPP-4 inhibitors | ↑ HF |
| Control group | ||
| Wang et al., 2014 [69] | SIT | ↑ HF (HR: 1.09, 95 % CI: 1.06–1.11, P < 0.001). |
| Control group | ||
| Chen et al., 2014 [70] | SIT | ↑ recurrent myocardial infarction (HR, 1.73; 95 % CI, 1.15–2.58; P = 0.008) |
| ↑ percutaneous coronary revascularization (HR, 1.43; 95 % CI, 1.04–1.95; P = 0.026) | ||
| Control group | ||
| Effects on liver | ||
| Belfort et al., 2006 [72] | PIO | ↓alanine transaminase (by 58 % vs. 34 %, P < 0.001) |
| ↑hepatic insulin sensitivity (by 48 % vs. 14 %, P = 0.008) | ||
| ↓liver fat (by 54 % vs. 0 %, P < 0.001) | ||
| ↓liver inflammation (P = 0.008) | ||
| ↓ballooning necrosis (P = 0.02) | ||
| Fibrosis not improved (P = 0.08) | ||
| PLB | ||
| Aithal et al., 2008 [73] | PIO | ↓ hepatocellular injury (P = 0.005) |
| ↓Mallory-Denk bodies (P = 0.004) | ||
| ↓ alanine aminotransferase level (−10.9 vs −36.2 u/L; P = 0.009) | ||
| ↓ gamma-glutamyltransferase level (−9.4 vs −41.2 u/L; P = 0.002) | ||
| ↓ ferritin (−11.3 vs −90.5 μg/L; P = 0.01) | ||
| Fibrosis improved (P = 0.05) | ||
| PLB | ||
| Sanyal et al., 2010 [74] | PIO | ↓ serum alanine and aspartate aminotransferase levels (P < 0.001) |
| ↓ insulin resistance (P = 0.03) | ||
| ↓ liver inflammation (P = 0.004) | ||
| ↓ ballooning necrosis (P = 0.08) | ||
| Fibrosis not improved (P = 0.12) | ||
| PLB | ||
| Ohki et al., 2012 [77] | SIT | ↓ aspartate aminotransferase (P = 0.47) |
| ↓ alanine aminotransaminase (P = 0.03) | ||
| ↓ gamma-glutamyltransferase (P = 0.01) | ||
| PIO | ↓ aspartate aminotransferase (P < 0.01) | |
| ↓ alanine aminotransaminase (P < 0.01) | ||
| ↓ gamma-glutamyltransferase (P < 0.01) | ||
| Iwasaki et al., 2011 [75] | SIT | ↓ alanine transaminase, aspartate aminotransferase, gamma-glutamyltransferase |
| Itou et al., 2012 [76] | SIT – case report | ↓ alanine transaminase, aspartate aminotransferase |
| ↓ insulin resistance | ||
| ↓ liver fat | ||
| Risk of development of oncological disease | ||
| Azoulay et al., 2013 [2] | PIO | ↑ bladder cancer (RR 1.83, 95 % CI 1.10–3.05) |
| Wei et al., 2013 [87] | PIO | ↓ bladder cancer (HR, 1.16, 95 % CI 0.83, 1.62) |
| Active control | ||
| Govindarajan et al., 2007 [34] | PIO | ↓lung cancer (RR, 0.67; 95 % CI, 0.51–0.87) |
| Active control | ||
| Mazzone et al., 2012 [56] | TZDs | ↓ lung cancer (OR 0.86, 95 % CI 0.4–1.85, p = 0.14) |
| MET | ↓ lung cancer (OR 0.48, 95 % CI 0.28–0.81, p = 0.006) | |
| Nelson et al., 2014 [31] | SIT - case report | ↑ pancreatitis |
| Girgis and Champion, 2011 [81] | VIL - case report | ↑ acute pancreatitis |
| Singh et al., 2013 [27] | EQW/SIT | ↑acute pancreatitis (OR 2.01, 95 % CI [1.37–3.18], P = 0.01) |
| Engel et al., 2013 [45] | SIT Comparator agent | Rates of malignancy (−0.05 (95 % CI −0.41, 0.30) |
| Rate of category of pancreatic cancer (adenocarcinoma of pancreas, pancreatic carcinoma, pancreatic carcinoma metastatic) (0.05 and 0.06 events per 100 patient-years in the sitagliptin and nonexposed groups, respectively) |
ROSI rosiglitazone, SAXA saxagliptin, АLO alogliptin, BMD bone mineral density, CVD cardiovascular disease, IS ischemic stroke