Table 3.
Effects of GLP-1 receptor antagonism on metabolic measures
| Change in measures (exendin minus vehicle) | Liraglutide | Sitagliptin | Diet | |||
|---|---|---|---|---|---|---|
| 2 weeks | 14 weeks | 2 weeks | 14 weeks | 2 weeks | 14 weeks | |
| Fasting measures | ||||||
| Fasting glucose, mg/dL | 11.0 ± 12.2* | 13.7 ± 11.7* | 9.5 ± 9.4* | 11.8 ± 6.5* | 11.0 ± 10.4* | 12.4 ± 11.1* |
| Fasting insulin, µU/mL | 0.4 ± 8.0 | −1.2 ± 10.6 | −6.2 ± 12.1* | −2.6 ± 9.8 | 0.3 ± 10.2 | 3.6 ± 11.9 |
| Fasting C-peptide, pg/mL | −192.0 ± 611.2 | 77.7 ± 856.9 | −281.0 ± 689.3 | 55.4 ± 477.8 | 71.9 ± 556.9 | −100.4 ± 638.5 |
| Fasting glucagon, pmol/L | 4.1 ± 5.9* | 2.5 ± 7.6* | 1.0 ± 7.4 | 1.7 ± 4.8 | 7.4 ± 15.7* | 1.3 ± 8.9 |
| Fasting GLP-1, pg/mL | NA | NA | 3.7 ± 8.9* | 2.6 ± 5.4 | 0.5 ± 1.2 | 0.7 ± 1.1 |
| Fasting GIP, pg/mL | −5.8 ± 22.0‡ | −2.7 ± 20.2 | −17.3 ± 69.4 | −7.2 ± 29.2 | −0.3 ± 9.7 | −0.9 ± 8.7 |
| HOMA-IR | 0.7 ± 2.3 | 0.4 ± 2.8 | −0.8 ± 2.7 | 0.1 ± 2.5 | 0.5 ± 2.6 | 1.8 ± 4.1* |
| HOMA2 | 0.01 ± 0.16 | −0.01 ± 0.21 | −0.10 ± 0.22 | −0.04 ± 0.19 | 0.01 ± 0.20 | 0.09 ± 0.25 |
| Postprandial measures | ||||||
| Glucose peak | 20.4 ± 12.9*‡ | 23.7 ± 17.1*†‡ | 14.6 ± 12.2* | 16.3 ± 13.0* | 10.6 ± 14.3* | 14.3 ± 8.6* |
| Glucose AUC | 2,696.8 ± 3,844.4*‡ | 3,804.8 ± 3,134.9* | 2,423.1 ± 2,581.6* | 3,673.9 ± 2,488.5* | 472.5 ± 5,138.7 | 2,542.5 ± 1,933.6* |
| Insulin peak | 23.7 ± 49.3* | 20.2 ± 56.7* | −2.0 ± 70.4 | 20.3 ± 40.0 | 1.8 ± 47.7 | 32.6 ± 64.2* |
| Insulin AUC | 3,506.5 ± 7,563.4* | 2,367.4 ± 8,779.3* | 1,065.0 ± 8,019.5 | 3,497.5 ± 5,296.0 | −682.1 ± 6,198.9 | 4,557.0 ± 8,114.0* |
| Insulin to glucose peak ratio | 0.1 ± 0.5† | 0.1 ± 0.5 | −0.2 ± 0.8* | 0.0 ± 0.3 | −0.1 ± 0.4 | 0.1 ± 0.5 |
| Insulin to glucose AUC ratio | 18.3 ± 72.1 | 4.6 ± 61.9 | −17.7 ± 78.1 | 6.4 ± 37.2 | −17.1 ± 55.6 | 22.1 ± 50.7 |
| C-peptide peak | 1,164.7 ± 2,228.5*‡ | 1,346.4 ± 2,358.9* | 273.1 ± 1,189.1 | 738.9 ± 1,569.8 | −88.6 ± 2,276.8 | 852.8 ± 1,755.9 |
| C-peptide AUC | 133,548.4 ± 423,882.7 | 162,669.3 ± 439,851.6* | 52,205.8 ± 191,460.0 | 128,087.3 ± 343,138.1 | 45,086.5 ± 461,294.5 | 92,812.5 ± 341,356.7 |
| C-peptide to glucose peak ratio | 4.5 ± 19.9‡ | 4.4 ± 18.1 | −3.4 ± 12.8 | −0.8 ± 8.5 | −5.5 ± 16.7 | 0.2 ± 14.0 |
| C-peptide to glucose AUC ratio | 812.8 ± 3,215.2 | −78.7 ± 3,470.3 | −1,282.6 ± 2,626.2 | −190.7 ± 2,795.7 | −254.9 ± 3,813.4 | −388.4 ± 2,925.0 |
| Glucagon peak | 8.9 ± 6.8*† | 8.3 ± 10.8*† | 1.8 ± 13.0 | 4.0 ± 6.6 | 12.8 ± 11.8* | 2.2 ± 5.7 |
| Glucagon AUC | 1,656.1 ± 1,743.5* | 1,627.5 ± 1,998.1*†‡ | 494.0 ± 1,975.8 | 779.3 ± 1,444.2 | 2,163.8 ± 2,677.2* | 86.8 ± 1,502.0 |
| GLP-1 peak, t0 adj | 19.1 ± 18.0*†‡ | 14.5 ± 12.5*† | 44.6 ± 38.6*‡ | 40.8 ± 32.5*‡ | 5.6 ± 5.0 | 4.7 ± 4.0 |
| GLP-1 AUC, t0 adj | 2,406.8 ± 2,524.3*† | 2,046.3 ± 1,750.6*† | 5,375.3 ± 4,705.0*‡ | 5,574.0 ± 3,981.5*‡ | 712.9 ± 820.1 | 778.0 ± 585.8 |
| GIP peak | 9.3 ± 153.9 | 42.9 ± 178.8 | −29.7 ± 262.6 | 22.4 ± 293.1 | −6.8 ± 208.3 | 13.8 ± 66.8 |
| GIP AUC | −2,417.8 ± 21,752.7 | 2,719.9 ± 15,916.0 | −6,977.8 ± 40,164.4 | −1,350.4 ± 28,709.6 | −1,874.5 ± 28,704.1 | −1,935.0 ± 13,497.1 |
| Matsuda index | −2.0 ± 4.3* | −1.3 ± 1.9*‡ | −0.2 ± 1.6 | −0.6 ± 1.3 | 0.4 ± 2.2 | 1.9 ± 8.6 |
| Disposition index | 3.2 ± 85.2 | 1.5 ± 44.2‡ | −7.4 ± 30.7 | −37.8 ± 135.1‡ | −12.0 ± 56.3 | 114.7 ± 440.2* |
| Insulinogenic index | −68.4 ± 465.1 | −24.9 ± 256.6‡ | −41.6 ± 498.6 | −16.1 ± 171.3‡ | −21.0 ± 809.6 | −428.3 ± 1,577.7* |
| InsAUC30/GluAUC30 | 6.5 ± 19.7‡ | 0.8 ± 15.8 | −0.1 ± 11.4 | −8.0 ± 37.4 | −8.0 ± 27.4 | 1.2 ± 19.9 |
All measures shown as mean ± SD difference exendin minus vehicle. NA, not accurate due to assay cross-reactivity with liraglutide; t0 adj, adjusted for time 0.
*
P < 0.05 vehicle vs. exendin(9-39).
†
P < 0.05 vs. sitagliptin.
‡
P < 0.05 vs. diet.