Exenatide BID |
|
|
|
|
|
|
|
|
Blevins et al. (2011) [51] (DURATION-5) |
24 |
252 |
(None, 1 or combination of Met, SU, TZD)+exenatide QW |
Exenatide 10 µg BID |
–1.4 |
2.1a (4.1a for exenatide QW) |
–1.2 |
0.07 LDL-C |
0.03 HDL-C |
0.01 TG |
Bunck et al. (2010) [48] |
52 |
69 |
Met+insulin glargine |
|
–3.9a
|
b
|
b
|
–61% hs-CRPa
|
Buse et al. (2009) [54] (LEAD-6) |
26 |
464 |
(Met±SU)+liraglutide |
|
–2.9 |
0.69a (+3.28a for liraglutide) |
–2.0 |
–0.40 LDL-C |
–0.05 HDL-C |
–0.23 TGc
|
–0.10 FFAc
|
–0.03 g/L ApoB |
Davies et al. (2009) [55] |
26 |
235 |
2 or 3 OADs+insulin glargine |
|
–2.73a
|
b
|
–2.9 |
–0.25 LDL-Ca
|
0.01 HDL-C |
–0.33 TG |
DeFronzo et al. (2010) [56] |
20 |
137 |
Met+TZD |
|
–2.8a
|
b
|
b
|
–0.05 LDL-Ca
|
0.02 HDL-C |
–0.34 TGa |
Derosa et al. (2010) [49] |
52 |
128 |
Met+SU |
|
–8.0a
|
b
|
b
|
↓hs-CRP (VNR)a
|
Drucker et al. (2008) [57] (DURATION-1) |
30 |
295 |
(Met, SU, TZD or any two combined)+exenatide QW |
|
–3.6 |
b
|
–3.4 |
+0.03 LDL-Cc |
–0.03 HDL-C |
–11% TG |
Klonoff et al. (2008) [58] |
3 years |
217 |
(Met±SU)+placebo |
|
–5.3a
|
b
|
–3.5a
|
–6% LDL-Ca
|
24% HDL-Ca
|
–12% TG-Ca
|
Moretto et al. (2008) [59] |
24 |
232 |
None+placebo |
|
–3.1a
|
b
|
–3.7a
|
–0.07 LDL-C |
0.02 HDL-C |
Exenatide QW |
|
|
|
|
|
|
|
|
Drucker et al. (2008) [57] (DURATION-1) |
30 |
295 |
(Met, SU, TZD, or any two combined)+exenatide BID |
Exenatide QW |
–3.7 |
b
|
–4.7 |
–0.13 LDL-Ca
|
–0.02 HDL-C |
–15% TG |
Buse et al. (2010) [60] (DURATION-1 extension) |
+22 (52 in total) |
295 |
(Met, SU, TZD, or any two combined)+exenatide BID or QW from DURATION-1 studies |
|
–4.1 (QW)–4.5 (BID→QW) |
b
|
–6.2a (QW)–3.8 (BID→QW) |
–9.6 mg/dL TC |
–0.7 mg/dL HDL-C |
–3.4 mg/dL LDL-C |
–15% TG |
MacConell et al. (2013) [61] (DURATION-1 extension) |
3 years |
295 |
(Met, SU, TZD, or any two combined)+exenatide BID→exenatide QW |
|
–2.3a
|
b
|
–2.1 |
–0.26 TC |
–0.18 LDL-C |
0.03 HDL-C |
–12% TG |
Bergenstal et al. (2010) [50] (DURATION-2) |
26 |
491 |
Met+(Sit or TZD) |
|
–2.3a
|
b
|
↓(VNR)a
|
↑HDL-Ca
|
–5% TG |
↓hs-CRPa
|
↓BNPa
|
Diamant et al. (2010) [53] (DURATION-3) |
26 |
456 |
(Met±SU)+insulin glargine |
|
–2.6a
|
4.0a
|
–3.0a
|
–0.05 LDL-C |
0.0 HDL-C |
–2.0 mg/dL hs-CRPa
|
Diamant et al. (2012) [52] (DURATION-3 extension) |
84 |
456 |
(Met±SU)+insulin glargine |
|
–2.1a
|
1.97a
|
–4.2a
|
–0.12 TC |
0.95 TG |
–2.05 mg/dL hs-CRP |
Diamant et al. (2014) [62] (DURATION-3 extension) |
3 years |
456 |
(Met±SU)+insulin glargine |
|
–2.49a
|
2 |
–2 |
–0.13 TCa
|
–0.17 LDL-Ca
|
0.05 HDL-Ca
|
1.02 TG |
–2.00 mg/dL CRPa
|
Russell-Jones et al. (2012) [63] (DURATION-4) |
26 |
820 |
None+(Met, TZD or Sit) |
|
–2.0 |
1.5 |
–1.3 |
No change in fasting serum lipids (VNR) |
Blevins et al. (2011) [51] (DURATION-5) |
24 |
252 |
(None, 1, or combination: Met, SU, TZD)+exenatide BID |
|
–2.3a
|
4.1a (2.1a for exenatide BID) |
–2.9a
|
–0.17 LDL-Ca
|
0.0 HDL-C |
0.01 TG |
Buse et al. (2013) [64] (DURATION-6) |
26 |
911 |
(Met, SU, Met+SU, or Met+TZD)+liraglutide |
|
–2.68 |
b
|
–2.48 (–3.45 for liraglutide) |
–0.06 TC |
0.02 HDL-C |
–0.05 LDL-C |
–2.19 nmol/L hs-CRP |
–4.45 ng/L BNP |
Liraglutide |
|
|
|
|
|
|
|
|
Marre et al. (2009) [65] (LEAD-1) |
26 |
1,041 |
SU+(TZD or TZD placebo) |
1.2 mg/day |
+0.3a
|
2–4a
|
–2.6–2.8 |
b
|
1.8 mg/day |
–0.2a
|
2–4a
|
–2.6–2.8 |
b
|
Nauck et al. (2009) [66] (LEAD-2) |
26 |
1,091 |
Met+(SU or placebo) |
1.2 mg/day |
–2.6a
|
2–3a
|
–2–3a
|
b
|
1.8 mg/day |
–2.8a
|
2–3a
|
–2–3a
|
b
|
Garber et al. (2009) [67] (LEAD-3) |
52 |
746 |
None+SU |
1.2 mg/day |
–2.1a
|
3.2a
|
–2.1 |
b
|
1.8 mg/day |
–2.5a
|
1.6 |
–3.6a
|
b
|
Garber et al. (2011) [68] (LEAD-3 extension) |
2 years |
746 |
None+SU |
1.2 mg/day |
–1.89a
|
2.04 |
–1.35 |
b
|
1.8 mg/day |
–2.70a
|
0.92 |
–2.37 |
b
|
Zinman et al. (2009) [69] (LEAD-4) |
26 |
533 |
(Met+TZD)+placebo |
1.2 mg/day |
–1.0a
|
b
|
–6.7a
|
–0.21 TC |
–0.28 LDL-Ca
|
–0.03 HDL-C |
–0.38 TGa
|
–0.03 FFAa
|
1.8 mg/day |
–2.0a
|
b
|
–5.6a
|
–0.20 TC |
–0.23 LDL-C |
–0.04 HDL-C |
–0.32 TG |
–0.05 FFAa
|
Russell-Jones et al. (2009) [70] (LEAD-5) |
26 |
581 |
(Met+SU)+(insulin glargine or placebo) |
1.8 mg/day |
–1.8a |
b
|
–4.0a
|
b
|
Buse et al. (2009) [54] (LEAD-6) |
26 |
464 |
(Met±SU)+exenatide |
1.8 mg/day |
–3.2 |
3.28 (0.69 for exenatide BID) |
–2.5 |
–0.44 LDL-C |
–0.04 HDL-C |
–0.41 TGa
|
–0.17 FFAa
|
–0.06 g/L ApoB |
Buse et al. (2010) [71] (LEAD-6 extension) |
+14 (40 in total) |
376 |
(Met±SU)+exenatideBID→liraglutide |
1.8 mg/day |
–0.9a
|
b
|
–3.8a
|
b
|
Pratley et al. (2010) [72] |
26 |
658 |
Met+Sit |
1.2 mg/day |
–2.86a
|
2.32 |
–0.55 |
–0.08 LDL-C |
0.00 HDL-C |
–0.19 TG |
–0.03 FFA |
–0.06 g/L ApoB |
1.8 mg/day |
–3.38a
|
3.94 |
–0.72 |
–0.05 LDL-C |
0.00 HDL-C |
–0.43 TG |
–0.07 FFA |
–0.07 g/L ApoB |
Pratley et al. (2011) [73] extension |
+26 (52 in total) |
436 |
Met+Sit |
1.2 mg/day |
–2.78a
|
1.72 |
–0.37 |
0.09 LDL-C |
–0.10 TG |
–0.07 FFA |
–0.03 g/L ApoB |
1.8 mg/day |
–3.68a
|
3.09 |
–2.55 |
0.09 LDL-C |
–0.32 TG |
–0.10 FFA |
–0.03 g/L ApoB |
Lixisenatide |
|
|
|
|
|
|
|
|
Rosenstock et al. (2013) [74] (GetGoal-X) |
24 |
634 |
Met+exenatide BID |
20 µg QD |
–2.8 |
0.1 |
–2.9 |
b
|
Rosenstock et al. (2014) [75] (GetGoal-S) |
24 |
859 |
(SU±Met)+placebo |
20 µg QD |
–1.76a
|
–0.1 |
Slight decrease (VNR) |
No relevant change in lipid levels (VNR) |
Albiglutide |
|
|
|
|
|
|
|
|
Nauck et al. (2016) [76] (HARMONY 2) |
52 |
309 |
None+placebo |
30 mg QW |
–0.39 |
2.5 |
–2.8 |
–0.312 TC |
–0.278 LDL-C |
0.051 HDL-C |
–0.379 TG |
–0.038 FFA |
50 mg QW |
–0.86 |
0.8 |
–1.3 |
–0.101 TC |
–0.130 LDL-C |
0.042 HDL-C |
0.014 TG |
–0.007 FFA |
Ahren et al. (2014) [77] (HARMONY 3) |
104 |
1,049 |
Met+(Sit, SU or placebo) |
30 mg QW |
–1.21a
|
1.3 |
–1.0 |
–0.07 TC |
–0.03 LDL-C |
0.04 HDL-C |
–0.20 TG |
Weissman et al. (2014) [78] (HARMONY 4) |
52 |
779 |
(Met±SU)+insulin glargine |
30 mg QW |
–1.06 |
1.0 |
–1.4 |
–2.1 mg/dL TC |
–1.8 mg/dL LDL-C |
2.1 mg/dL HDL-C |
–17.3 mg/dL TG |
Pratley et al. (2014) [79] (HARMONY 7) |
32 |
841 |
(Met, TZD, SU, or any combination)+liraglutide 1.8 mg QD |
30 mg→ 50 mg QW at week 6 |
–0.64 |
5.7 at week 4 (max) |
<±1.0 |
Investigator-assessed cardiovascular AE: 8.2% (forliraglutide: 10.5%) |
Returned to baseline within study period |
Dulaglutide |
|
|
|
|
|
|
|
|
Wysham et al. (2014) [80] (AWARD-1) |
52 |
976 |
(Met±TZD)+(exenatide BID or placebo→dulaglutide at week 26) |
0.75 mg/day |
–0.20a
|
1.56 (2.80a at week 26) |
1.62 (–0.36a at week 26) |
–0.09 TC |
–0.08 LDL-C |
0.00 HDL-C |
0.04 TG |
1.5 mg/day |
–1.30a
|
1.68 (2.80a at week 26) |
0.83 (0.11a at week 26) |
–0.12 TC |
–0.06 LDL-C |
0.05 HDL-C |
–0.26 TGa
|
Giorgino et al. (2015) [81] (AWARD-2) |
78 |
810 |
(Met±SU)+insulin glargine |
0.75 mg/day |
–1.33a
|
0.61a
|
–0.59 |
0.03 TC |
–0.02 LDL-C |
–0.02 HDL-C |
0.03 TG |
1.5 mg/day |
–1.87a
|
1.31a
|
–0.70 |
0.02 TC |
0.00 LDL-C |
0.00 HDL-C |
0.05 TG |
Umpierrez et al. (2014) [82] (AWARD-3) |
52 |
807 |
None+(Met+placebo) |
0.75 mg/day+oral placebo |
–1.36 at week 26 (VNR for week 52) |
1.6 |
–2.7 |
–1% TCa
|
–2% LDL-Ca
|
2% HDL-C |
–1% TG |
1.5 mg/day+oral placebo |
–2.29 at week 26 (VNR for week 52) |
1.8 |
–0.1 |
–2% TC |
–2% LDL-Ca
|
5% HDL-C |
–4% TG |
Blonde et al. (2015 )[83] (AWARD-4) |
52 |
884 |
Insulin±OADs→(insulin lispro+Met)+insulin glargine |
0.75 mg/day |
+0.18 at week 26 (VNR for week 52) |
2.27 |
1.04 |
0.94% TC |
–1.02% LDL-C |
3.54% HDL-Ca
|
5.73% TG |
1.5 mg/day |
–0.87 at week 26 (VNR for week 52) |
2.38a
|
–0.26 |
0.00% TC |
–1.95% LDL-C |
2.44% HDL-Ca
|
2.96% TG |
Nauck et al. (2014) [84] (AWARD-5) |
52 |
1,098 |
(None, 1, or combination of OAD)+Sit or placebo (placebo→Sit at week 26) |
0.75 mg/day |
–2.60a
|
2.1a
|
–0.5 |
–0.03 TC |
0.02 LDL-C |
0.07 HDL-C |
–0.15 TG |
1.5 mg/day |
–3.03a
|
2.4a
|
–0.8 |
–0.03 TC |
–0.06 LDL-Ca
|
0.05 HDL-C |
–0.16 TG |
Weinstock et al. (2015) [85] (AWARD-5 extension) |
2 years |
1,098 |
(None, 1, or combination of OAD)+Sit or placebo (placebo→Sit at week 26) |
0.75 mg/day |
–2.39 |
2.8a
|
1.3 |
No significant changes in lipids (VNR) |
1.5 mg/day |
–2.88a
|
2.3a
|
–0.1 |
Dungan et al. (2014) [86] (AWARD-6) |
26 |
599 |
Met+liraglutide |
1.5 mg/day |
–2.90 |
2.37 |
–3.36 |
b
|