1Division of Endocrinology and Metabolism, Department of Internal Medicine, International St. Mary’s Hospital, Catholic Kwandong University College of Medicine, Incheon, Korea
2Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, Korea
3Medical information and Pharmacovigilance Team, CKD Pharmaceutical Corp., Seoul, Korea
4Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
Copyright © 2021 Korean Diabetes Association
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
CONFLICTS OF INTEREST
The authors report no potential conflict of interest relevant to this article. Laboratory data analysis and calibration support was provided by Chong Kun Dang Pharmaceutical Corporation, Seoul, Korea.
FUNDING
None
Parameter | Value |
---|---|
Tmax, hra | 1.00±0.50 |
Cmax, µg/L | 50.0±7.9 |
AUCinf, µg/hr/L | 379.0±44.6 |
CL/F, L/hr | 1.33±0.15 |
t1/2, hr | 7.82±0.43 |
fe, % | Negligibleb |
Protein binding, % | 99.3–99.9 |
Metabolism | CYP 3A4 (main), 2C19 and 2D6 |
Metabolites | M7 (O-demethylation; main), M9 (N-demethylation) |
Values are presented as mean±standard deviation unless indicated otherwise.
Tmax, time to Cmax; Cmax, maximum plasma concentration; AUCinf, area under concentration–time curve from 0 to infinity; CL/F, oral clearance; t1/2, elimination half-life; fe, fraction excreted unchanged in urine; CYP, cytochrome P450.
a Median and range are presented for Tmax,
b Fraction of lobeglitazone excreted unchanged in urine was below the lower limit of quantification (0.2 ng/mL).
Variable | Lobeglitazone (0.5 mg/day) | Pioglitazone (30 mg/day) | |
---|---|---|---|
Monotherapy, short-term [41,47,48] | |||
Week | 24 | 16 | 26 |
Baseline HbA1c, % | 7.85 | 7.50 | 10.2 |
Change in HbA1c (placebo subtracted), % | −0.44 (−0.60) | −0.80 (−0.60) | −0.30 (−1.0) |
Monotherapy, long-term [42,49,50] | |||
Week | 52 | 52 | 52 |
Baseline HbA1c, % | 7.79 | 8.69 | 8.70 |
Change in HbA1c, % | −0.50 | −1.41a | −1.40a |
Add-on to metformin [43,51] | |||
Week | 24 | 24 | 24 |
Baseline HbA1c, % | 7.93 | 7.96 | 8.40 |
Change in HbA1c, % | −0.74 | −0.74a | −0.98 |
Variable | Total cholesterol, mg/dL | LDL-C, mg/dL | Small dense LDL, % | HDL-C, mg/dL | Triglyceride, mg/dL | Free fatty acid, µEq/L |
---|---|---|---|---|---|---|
Monotherapy [41] | ||||||
Lobeglitazone | ||||||
Baseline | 178.70 | 109.0 | 8.10 | 48.69 | 137.51 | 622.28 |
Change | 6.0 | 0.95 | −1.7a,b | 4.3a,b | −19.06a,b | −60.39a,b |
Placebo | ||||||
Baseline | 188.26 | 114.76 | 9.51 | 46.33 | 177.14 | 699.57 |
Change | 4.84 | −2.64 | 0.62 | 0.76 | 16.14 | −1.0 |
Add-on to metformin [43] | ||||||
Lobeglitazone | ||||||
Baseline | 162.03 | 88.55 | 4.02 | 49.50 | 139.95 | 680.0 |
Change | 6.96a | 4.64a | −1.23a | 4.64a | −12.40a | −100.0a |
Pioglitazone | ||||||
Baseline | 169.76 | 95.13 | 5.07 | 49.11 | 156.78 | 660.0 |
Change | 7.35a | 4.64a | −1.06a | 5.80a | −19.49a | −90.0a |
Variable |
Monotherapy (24 weeks) [41] |
Monotherapy-extension (52 weeks)a [42] |
Add-on to metformin (24 weeks) [43] |
|||
---|---|---|---|---|---|---|
Lobeglitazone (n=112) | Placebo (n=58) | Maintenance group (n=64) | Switch group (n=29) | Lobeglitazone (n=128) | Pioglitazone (n=125) | |
Any AE | 55 (49.1) | 30 (51.7) | 41 (64.1) | 18 (62.1) | 66 (51.6) | 64 (51.2) |
Drug-related AE | 10 (8.9) | 3 (5.2) | 8 (12.5) | 2 (6.9) | 8 (6.3) | 6 (4.8) |
Serious AE | 4 (3.6) | 0 | 3 (4.7) | 0 | 7 (5.5) | 6 (4.8) |
Frequent AE | ||||||
Hyperglycemia | 3 (2.7) | 4 (6.9) | 3 (4.7) | 0 | <3%b | <3%b |
Nasopharyngitis | 6 (5.4) | 0 | 3 (4.7) | 0 | 6 (4.7) | 10 (8.0) |
URTI | 2 (1.7) | 3 (5.2) | 8 (12.5) | 1 (3.5) | 2 (1.6) | 4 (3.2) |
Peripheral edema | 4 (3.6) | 0 | 2 (3.1) | 0 (0) | 5 (3.9) | 2 (1.6) |
Headache | 3 (2.7) | 2 (3.5) | 3 (4.7) | 1 (3.5) | <3%b | <3%b |
Hematuria | 3 (2.7) | 3 (5.2) | 3 (4.7) | 2 (6.9) | 0 | 0 |
AE of special interest | ||||||
Hypoglycemia | 0 | 0 | 0 | 0 | 1 (0.8) | 3 (2.4) |
Heart failure | 0 | 0 | 0 | 0 | <3%b | <3%b |
Ischemic heart disease | 0 | 0 | 0 | 0 | <3%b | <3%b |
Neoplasm | 1c (0.9) | 0 | 1c (1.6) | 0 | 0 | 1d (0.8) |
Values are presented as number (%).
AE, adverse event; URTI, upper respiratory tract infection.
a Maintenance group received lobeglitazone for weeks 0–52. Switch group received placebo for weeks 0–24 and lobeglitazone for weeks 25–52,
b Exact number of cases not presented in the published article,
c Lung cancer, not considered to be related to lobeglitazone by investigators,
d Colon cancer, not considered to be related to pioglitazone by investigators.
Parameter | Value |
---|---|
Tmax, hr |
1.00±0.50 |
Cmax, µg/L | 50.0±7.9 |
AUCinf, µg/hr/L | 379.0±44.6 |
CL/F, L/hr | 1.33±0.15 |
t1/2, hr | 7.82±0.43 |
fe, % | Negligible |
Protein binding, % | 99.3–99.9 |
Metabolism | CYP 3A4 (main), 2C19 and 2D6 |
Metabolites | M7 (O-demethylation; main), M9 (N-demethylation) |
Parameter | ESRD | Normal | Geometric mean ratio | 90% CI |
---|---|---|---|---|
Cmax, ng/mL | 45.56±10.815 | 46.43±7.157 | 0.9883 | 0.8441–1.1572 |
AUC48, ng/hr/mL | 669.29±266.348 | 750.19±206.071 | 0.8683 | 0.6319–1.1931 |
AUCinf, ng/hr/mL | 803.27±366.626 | 964.57±313.819 | 0.8039 | 0.5507–1.1737 |
Variable | Lobeglitazone (0.5 mg/day) | Pioglitazone (30 mg/day) | |
---|---|---|---|
Monotherapy, short-term [41,47,48] | |||
Week | 24 | 16 | 26 |
Baseline HbA1c, % | 7.85 | 7.50 | 10.2 |
Change in HbA1c (placebo subtracted), % | −0.44 (−0.60) | −0.80 (−0.60) | −0.30 (−1.0) |
Monotherapy, long-term [42,49,50] | |||
Week | 52 | 52 | 52 |
Baseline HbA1c, % | 7.79 | 8.69 | 8.70 |
Change in HbA1c, % | −0.50 | −1.41 |
−1.40 |
Add-on to metformin [43,51] | |||
Week | 24 | 24 | 24 |
Baseline HbA1c, % | 7.93 | 7.96 | 8.40 |
Change in HbA1c, % | −0.74 | −0.74 |
−0.98 |
Variable | Total cholesterol, mg/dL | LDL-C, mg/dL | Small dense LDL, % | HDL-C, mg/dL | Triglyceride, mg/dL | Free fatty acid, µEq/L |
---|---|---|---|---|---|---|
Monotherapy [41] | ||||||
Lobeglitazone | ||||||
Baseline | 178.70 | 109.0 | 8.10 | 48.69 | 137.51 | 622.28 |
Change | 6.0 | 0.95 | −1.7 |
4.3 |
−19.06 |
−60.39 |
Placebo | ||||||
Baseline | 188.26 | 114.76 | 9.51 | 46.33 | 177.14 | 699.57 |
Change | 4.84 | −2.64 | 0.62 | 0.76 | 16.14 | −1.0 |
Add-on to metformin [43] | ||||||
Lobeglitazone | ||||||
Baseline | 162.03 | 88.55 | 4.02 | 49.50 | 139.95 | 680.0 |
Change | 6.96 |
4.64 |
−1.23 |
4.64 |
−12.40 |
−100.0 |
Pioglitazone | ||||||
Baseline | 169.76 | 95.13 | 5.07 | 49.11 | 156.78 | 660.0 |
Change | 7.35 |
4.64 |
−1.06 |
5.80 |
−19.49 |
−90.0 |
Variable | Monotherapy (24 weeks) [41] |
Monotherapy-extension (52 weeks) |
Add-on to metformin (24 weeks) [43] |
|||
---|---|---|---|---|---|---|
Lobeglitazone (n=112) | Placebo (n=58) | Maintenance group (n=64) | Switch group (n=29) | Lobeglitazone (n=128) | Pioglitazone (n=125) | |
Any AE | 55 (49.1) | 30 (51.7) | 41 (64.1) | 18 (62.1) | 66 (51.6) | 64 (51.2) |
Drug-related AE | 10 (8.9) | 3 (5.2) | 8 (12.5) | 2 (6.9) | 8 (6.3) | 6 (4.8) |
Serious AE | 4 (3.6) | 0 | 3 (4.7) | 0 | 7 (5.5) | 6 (4.8) |
Frequent AE | ||||||
Hyperglycemia | 3 (2.7) | 4 (6.9) | 3 (4.7) | 0 | <3% |
<3% |
Nasopharyngitis | 6 (5.4) | 0 | 3 (4.7) | 0 | 6 (4.7) | 10 (8.0) |
URTI | 2 (1.7) | 3 (5.2) | 8 (12.5) | 1 (3.5) | 2 (1.6) | 4 (3.2) |
Peripheral edema | 4 (3.6) | 0 | 2 (3.1) | 0 (0) | 5 (3.9) | 2 (1.6) |
Headache | 3 (2.7) | 2 (3.5) | 3 (4.7) | 1 (3.5) | <3% |
<3% |
Hematuria | 3 (2.7) | 3 (5.2) | 3 (4.7) | 2 (6.9) | 0 | 0 |
AE of special interest | ||||||
Hypoglycemia | 0 | 0 | 0 | 0 | 1 (0.8) | 3 (2.4) |
Heart failure | 0 | 0 | 0 | 0 | <3% |
<3% |
Ischemic heart disease | 0 | 0 | 0 | 0 | <3% |
<3% |
Neoplasm | 1 |
0 | 1 |
0 | 0 | 1 |
Values are presented as mean±standard deviation unless indicated otherwise. Tmax, time to Cmax; Cmax, maximum plasma concentration; AUCinf, area under concentration–time curve from 0 to infinity; CL/F, oral clearance; t1/2, elimination half-life; fe, fraction excreted unchanged in urine; CYP, cytochrome P450. Median and range are presented for Tmax, Fraction of lobeglitazone excreted unchanged in urine was below the lower limit of quantification (0.2 ng/mL).
Values are presented as mean±standard deviation. ESRD, end-stage renal disease; CI, confidence interval; Cmax, maximum plasma concentration; AUC48, area under concentration–time curve from 0 to 48 hours; AUCinf, area under concentration–time curve from 0 to infinity.
HbA1c, glycosylated hemoglobin. Study design allowed pioglitazone dose-titration to 45 mg/day, Study used pioglitazone 15 mg/day. All pioglitazone data not marked with superscript a or b are from studies which used pioglitazone 30 mg once a day.
LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol. P<0.05 vs. baseline, P<0.05 vs. placebo.
Values are presented as number (%). AE, adverse event; URTI, upper respiratory tract infection. Maintenance group received lobeglitazone for weeks 0–52. Switch group received placebo for weeks 0–24 and lobeglitazone for weeks 25–52, Exact number of cases not presented in the published article, Lung cancer, not considered to be related to lobeglitazone by investigators, Colon cancer, not considered to be related to pioglitazone by investigators.