One Week’s Treatment With the Long-Acting Glucagon-Like Peptide 1 Derivative Liraglutide (NN2211) Markedly Improves 24-h Glycemia and α- and β-Cell Function and Reduces Endogenous Glucose Release in Patients with Type 2 Diabetes
Article Figures & Tables
Figures
- FIG. 1.
Flow sheet illustrating the procedures on study day 9. See text for details.
- FIG. 2.
Twenty-four-hour profiles of plasma glucose (A), serum FFAs (B), serum insulin (C), and plasma glucagon (D) (means ± SEM), day 8. ○, placebo; •, liraglutide; □, meals. (Statistical details are listed in Table 1.)
- FIG. 3.
Fasting EGR, GNG, and GLY, day 9. Data are means ± SEM. □, placebo; ▪, liraglutide; *P < 0.05, liraglutide vs. placebo.
- FIG. 4.
Plasma glucose (A) and serum insulin (B) concentrations during an intravenous glucose bolus, hyperglycemic clamp, and arginine stimultion test, day 9. ○, placebo; •, liraglutide, ▿, glucose bolus (25 g); ⊡, arginine bolus (5 g). Plasma glucagon (C) is depicted from 1105. Steady state of hyperglycemic clamp was in the interval 1045–1115. The insert in the middle panel is a blow-up of the first-phase insulin response. Data are means ± SEM. (Statistical details are listed in Table 2.)
- FIG. 5.
Concentration profiles of liraglutide. Dosing time was 0730. Gray lines indicate individual concentration profiles; black line indicates mean ± SEM.
Tables
- TABLE 1
Twenty-four-hour profiles and fasting values
Liraglutide Placebo P Fasting values Plasma glucose (mmol/l) 8.06 ± 0.52 9.39 ± 0.76 0.078 Plasma glucose day 9 (mmol/l) 7.56 ± 0.42 9.20 ± 0.78 0.025 FFA (mmol/l) 0.52 ± 0.03 0.51 ± 0.03 0.536 Insulin (pmol/l) 95.6 ± 15.1 87.2 ± 17.9 0.513 ISR (nmol/h) 17.7 ± 2.0 16.1 ± 2.1 0.206 Proinsulin/insulin ratio 0.17 ± 0.04 0.27 ± 0.05 0.009 Glucagon (pg/ml) 92.8 ± 7.2 94.5 ± 5.6 0.586 24-h total AUCs Plasma glucose (mmol · l−1 · h) 187.5 ± 14.0 232.3 ± 21.9 0.014 FFA (mmol · l−1 · h) 8.54 ± 0.51 8.65 ± 0.68 0.876 Insulin (pmol · l−1 · h) 3,854 ± 581 4,154 ± 881 0.375 ISR (nmol) 566.1 ± 55.1 561.6 ± 72.6 0.982 Glucagon (pg · ml−1 · h) 2,179 ± 118 2,371 ± 135 0.037 Postprandial total AUCs Plasma glucose 8–12 h (mmol · l−1 · h) 38.66 ± 3.52 47.51 ± 3.95 0.010 Plasma glucose 12–16 h (mmol · l−1 · h) 32.52 ± 2.92 41.89 ± 4.54 0.017 Plasma glucose 18–22 h (mmol · l−1 · h) 33.76 ± 2.50 41.10 ± 3.94 0.016 Insulin 8–12 h (pmol · l−1 · h) 999 ± 173 1,056 ± 253 0.512 Insulin 12–16 h (pmol · l−1 · h) 723 ± 107 808 ± 162 0.312 Insulin 18–22 h (pmol · l−1 · h) 1,017 ± 160 1,117 ± 221 0.392 Proinsulin/insulin ratio 8–12 h 0.12 ± 0.03 0.19 ± 0.04 0.008 Glucagon 8–12 h (pg · ml−1 · h) 383.0 ± 22.8 413.4 ± 25.6 0.080 Glucagon 12–16 h (pg · ml−1 · h) 362.6 ± 18.6 374.2 ± 19.5 0.384 Glucagon 18–22 h (pg · ml−1 · h) 397.3 ± 23.9 470.1 ± 35.2 0.009 Data are means ± SEM. Twenty-four-hour AUCs were calculated from samples obtained from 0800 to 0800. Fasting values were calculated from samples taken at 0730 and 0800 on days 8 and 9.
- TABLE 2
Islet cell function tests, insulin sensitivity, and disposition index
Liraglutide Placebo P Intravenous glucose tolerance test Insulin total AUC 9.15–9.32 h (pmol · l−1 · h) 55.45 ± 9.93 34.26 ± 6.4 0.008 Maximal insulin concentration 9.15–9.32 h (pmol/l) 262.6 ± 47.5 166.5 ± 32.4 0.007 Hyperglycemic clamp, steady state Insulin concentration (pmol/l) 929.6 ± 262.9 271.9 ± 53.3 0.015 Proinsulin/insulin ratio 0.09 ± 0.02 0.18 ± 0.03 0.001 Glucagon concentration (pg/ml) 55.5 ± 3.7 66.7 ± 3.5 0.005 GIR/average serum insulin (arbitrary units) 0.13 ± 0.03 0.15 ± 0.04 0.392 Arginine stimulation test Insulin total AUC 11.15–11.45 h (pmol · l−1 · h) 799.6 ± 190 307.2 ± 65.5 0.004 Maximal insulin concentration (pmol/l) 2,539 ± 523 1,518 ± 296 0.005 Glucagon total AUC 11.15–11.45 h (pg · l−1 · h) 40.7 ± 2.5 48.7 ± 3.0 0.012 Maximal glucagon concentration (pg/ml) 162.0 ± 13.7 193.4 ± 14 0.034 HOMA analysis β-Cell function (% of normal) 59.95 ± 8.84 46.07 ± 9.86 0.010 Insulin resistance (fold normal) 4.09 ± 0.84 4.74 ± 1.15 0.373 Disposition index (pmol/l*HOMA-R) 80.4 ± 14 41.9 ± 5 0.008 Data are means ± SEM. GIR, glucose infusion rate.
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