Introduction
Guideline recommendations
Insulin-like growth factor-1
Growth hormone
Oral glucose tolerance test
Study comparison
Pharmacokinetics
Aim
Methods
In- and exclusion criteria
Search strategies
Study selection and data extraction
Results
IGF-1 analysis | Number of studies (%) | References |
---|---|---|
Method | ||
1 Fasting sample | 13 (27%) | |
1 Sample | 12 (25%) | |
Mean of 2 samples (30 min and 1 min before drug administration) | 1 (2%) | [46] |
Not reported | 22 (46%) | |
Reported units | ||
ULN corrected | 29 (60%) | |
ng/ml | 21 (44%) | |
SD-score | 2 (4%) | |
ng/dl | 1 (2%) | [31] |
nmol/L | 1 (2%) | [57] |
Not reported | 3 (6%) | |
IGF-1 cut-off for biochemical control | ||
< ULN | 41 (85%) | |
< 1.2x ULN | 6 (13%) | |
< 1.3x ULN | 2 (4%) | |
< 1.1x ULN | 1 (2%) | [32] |
< 1.5x ULN | 1 (2%) | [26] |
> 20% decrease from baseline | 1 (2%) | [21] |
> 50% decrease from baseline | 1 (2%) | [28] |
No cut-off reported/used | 1 (2%) | [19] |
Summary statistics | ||
% Biochemical control | 41 (85%) | |
Mean ± SD | 20 (42%) | |
Individual ULN corrected levels | 17 (35%) | |
% Change mean ± SD | 10 (21%) | |
Median (range) | 10 (21%) | |
Median (IQR) | 9 (19%) | |
% Biochemical control [95% CI] no method reported | 8 (17%) | |
Mean ± SD [range] | 5 (10%) | |
Mean ± SE | 5 (10%) | |
% Change individual concentrations | 4 (8%) | |
Mean | 4 (8%) | |
% Change median | 3 (6%) | |
% Change median [range] | 3 (6%) | |
% Change median [IQR] | 3 (6%) | |
Individual IGF-1 concentrations | 3 (6%) | |
% Change mean | 2 (4%) | |
% Change mean [95% CI] | 2 (4%) | |
Geometric mean [95% CI] | 2 (4%) | |
% Biochemical control [90% exact CI] Clopper-Pearson exact 2-sided 90% CI | 1 (2%) | [37] |
% Change mean ± SD [Range] | 1 (2%) | [65] |
% Change mean [SEM] | 1 (2%) | [23] |
Geometric mean [68% CI] | 1 (2%) | [40] |
Mean ± SE [range] | 1 (2%) | [58] |
Median | 1 (2%) | [42] |
Time to nadir IGF-1 (mean ± SD) | 1 (2%) | [65] |
IGF-1 hormone assay reported | ||
Yes (%) | 40 (83%) |
GH analysis | Number of studies | References |
---|---|---|
Method | ||
1 Random sample | 10 (23%) | |
1 Fasting sample | 8 (18%) | |
Mean of 5 samples (2 h period) | 8 (18%) | |
Mean of 2/3 fasting samples (15–30 min interval) | 1 (2%) | [31] |
Mean of 3 fasting samples (1 h interval) | 1 (2%) | [23] |
Mean of 4 samples (30 min interval) | 1 (2%) | [46] |
Mean of 4 samples (1 h interval) | 1 (2%) | [44] |
Mean of 4 samples (4 h interval) | 1 (2%) | [48] |
Mean of 5 samples (10–15 min interval) | 1 (2%) | [29] |
Mean of 6 samples (2.5 h period) | 1 (2%) | [22] |
Mean of 8–10 samples (1 h interval) | 1 (2%) | [32] |
Not reported | 14 (32%) | |
GH cut-off for biochemical control | ||
< 2.5 ng/ml | 31 (70%) | |
< 1 ng/ml | 16 (36%) | |
> 20% decrease from baseline | 2 (5%) | |
< 1.5 ng/ml | 1 (2%) | [45] |
< 2 ng/ml | 1 (2%) | [19] |
< 5 ng/ml | 1 (2%) | [19] |
> 50% decrease from baseline | 1 (2%) | [44] |
No cut-off reported/used | 8 (18%) | |
Summary statistics | ||
% Biochemical control | 31 (70%) | |
Mean ± SD | 18 (41%) | |
Individual concentrations | 13 (30%) | |
Median (IQR) | 10 (23%) | |
% Biochemical control [95% CI] (no method reported) | 8 (18%) | |
% Change from baseline mean + SD | 7 (16%) | |
Median [range] | 7 (16%) | |
Mean | 4 (9%) | |
Mean ± SD [range] | 4 (9%) | |
% Change from baseline median | 3 (7%) | |
% Change from baseline median [range] | 3 (7%) | |
% Change from baseline median (IQR) | 3 (7%) | |
Mean ± SE | 3 (7%) | |
% Change from baseline mean | 2 (5%) | |
% Change from baseline mean (95% CI) | 2 (5%) | |
Geometric mean [95% CI] | 2 (5%) | |
Mean [range] | 2 (5%) | |
Range | 2 (5%) | |
% Biochemical control [90% exact CI] (Clopper-Pearson exact 2-sided 90% CI) | 1 (2%) | [37] |
% Change from baseline individual | 1 (2%) | [31] |
% Change from baseline mean [range] | 1 (2%) | [31] |
Geometric mean [68% CI] | 1 (2%) | [40] |
Maximum observed GH concentration | 1 (2%) | [26] |
Median | 1 (2%) | [42] |
Proportion above 40 ng/ml | 1 (2%) | [26] |
Growth hormone assay reported | ||
Yes (%) | 34 (77%) |
OGTT analysis | Number of studies (%) | References |
---|---|---|
Method | ||
2 h period: pre-dose, 30, 60, 120 min | 1 (9%) | [24] |
2 h period: 30, 60, 90, 120 min | 1 (9%) | [45] |
3 h period: pre-dose, 30, 60, 90, 120, 180 min | 1 (9%) | [33] |
Not reported | 8 (73%) | |
Glucose administration | ||
75 g | 5 (45%) | |
Not defined | 6 (55%) | |
Nadir cut-off for biochemical control | ||
< 1 ng/ml | 5 (45%) | |
< 0.4 ng/ml | 1 (9%) | [67] |
< 1 µg/dl | 1 (9%) | [61] |
< 2 mU/L | 1 (9%) | [27] |
No cut-off reported/used | 4 (36%) | |
Summary statistics | ||
% Biochemical control | 5 (45%) | |
Individual levels | 3 (27%) | |
Mean ± SD | 3 (27%) | |
Median (IQR) | 3 (27%) | |
% Nadir change from baseline mean ± SD | 1 (9%) | [24] |
Mean ± SD [range] | 1 (9%) | [30] |
Mean ± SD pre-glucose GH | 1 (9%) | [24] |
Median | 1 (9%) | [62] |
Median (IQR) pre-glucose GH | 1 (9%) | [24] |
Growth hormone assay reported | ||
Yes (%) | 7 (64%) |
Author | Number of samples per subject | Drug | Study design | Analysis summary |
---|---|---|---|---|
Lanreotide
| ||||
Garrido et al. [20] | 10 | Lanreotide autogel | Phase II, multicenter, randomized in acromegaly patients | Population PK/PD model linking the PK to individual GH (mean of 7 measurements with 30 min interval) and IGF-1 response |
Shimatsu et al. [44] | Not reported | Lanreotide | Phase II multicenter, open-label, randomized, parallel-group and phase III open-label, dose-adjustment, long-term treatment | Mean ± SD of Cmax, AUC and Cmin at sampled time points |
Giustina et al. [21] | 3 | Lanreotide autogel | Prospective, multicenter, randomized, open-label | Graphical analysis of individual serum concentrations and mean of 2 individual serum concentrations versus IGF-1 concentrations, with linear regression |
Octreotide
| ||||
Gadelha et al. [35] | 25 | Octreotide implant | Phase II, open-label, randomized | Mean ± SD of Cmax, AUC0−6 months, tmax. Graphical analysis of concentrations with mean ± SD |
Chieffo et al. [36] | 16 | Octreotide LAR Octreotide implant | Phase III, open-label, multicenter, randomized | Graphical analysis with mean ± SE at sampled time points per cohort |
Melmed et al. [34] | 14 | Oral octreotide | Phase III, multicenter, open-label, dose-titration | Mean ± SD for the C0, AUC and t1/2. Graphical analysis showing the mean ± SE |
Pasireotide
| ||||
Petersenn et al. [46] | 3 per scheduled visit, with ~ 20 visits per subject | Pasireotide | Open-ended extension of a phase II study | Individual dose normalized Ctrough concentration–time profiles |
Petersenn et al. [22] | 16 | Pasireotide LAR | Phase I, randomized, multicenter, open-label | Graphical analysis of mean ± SE Ctrough concentrations over 84 days and mean ± SE of post-first injection day. Median and mean ± SD for the Cmax, Ctrough, AUC and accumulation ratio |
Pegvisomant
| ||||
Higham et al. [66] | 2 | Pegvisomant | Prospective, multicenter, open-label | Mean ± SD of concentrations at 2 time points |