1LG Life Sciences Ltd., R&D Park, Daejeon, Korea.
2Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
3Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Copyright © 2016 Korean Diabetes Association
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Variable | Generic name (brand name) | ||||||
---|---|---|---|---|---|---|---|
Gemigliptin (Zemiglo) | Sitagliptin (Januvia) | Vildagliptin (Galvus) | Saxagliptin (Onglyza) | Linagliptin (Tragenta) | Alogliptin (Nesina) | Teneligliptin (Tenelia) | |
Therapeutic dose, mg/day | 50 | 100 | 100 (50×2) | 5 | 5 | 25 | 20 |
Dosing frequency | Once daily | Once daily | Twice daily | Once daily | Once daily | Once daily | Once daily |
Chemistry [10,11] | |||||||
Chemical structure | Pyrimidino piperidine derivative | Triazole pyrazine derivative | Cyanopyrrolidine | Cyanopyrrolidine | Xanthine derivative | Modified pyrimidinedione | L-prolylthiazolidine |
Peptidomimetic | Peptidomimetic | Peptidomimetic | Peptidomimetic | Non-peptidomimetic | Non-peptidomimetic | Peptidomimetic | |
Pharmacodynamics profiles [6,12,13,14] | |||||||
Binding mode | S1, S2, S2 extensive subsites | S1, S2, S2 extensive subsites | S1, S2 subsites | S1, S2 subsites | S1, S2 & S1', S2' subsites | S1, S2 & S1', S2' subsites | S1, S2, S2 extensive subsites |
Potency IC50, nmol/L | 6.3 | 19 | 62 | 50 | 1 | 24 | 1.8 |
Selectivity (fold) | High | High | Moderate | Moderate | Moderate | High | High |
DPP-8 | >27,000 | >2,600 | 270 | 390 | 40,000 | >14,000 | 700 |
DPP-9 | >23,000 | >5,500 | 32 | 77 | >10,000 | >14,000 | 1,500 |
FAP-α | >41,000 | >5,500 | 280 | >4,000 | 89 | >14,000 | >11,000 |
Pharmacokinetics profiles [7,8,9,10,11,12] | |||||||
Absorption | Rapid | Rapid | Rapid | Rapid | Rapid | Rapid | Rapid |
No effect of food | No effect of food | No effect of food | No effect of food | No effect of food | No effect of food | No effect of food | |
Cmax | 62.7 ng/mL | 959 nM | 397 ng/mL | 24 ng/mL (parent drug) | 9.6 nM | 110 ng/mL | 275 ng/mL |
47 ng/mL (metabolite) | |||||||
Metabolism | Metabolized by ~10% to LC15-0636 | Modest metabolism (~16%) | Metabolized by ~55% to LAY151 | Metabolized to the active metabolite M2 | Minimally metabolism | Minimally metabolism | Metabolized by ~65.6% |
Elimination half-life (t1/2), hr | 17.1 | 8–14 | 1.5–4.5 | 2–4 (parent drug) | 97–260 | 12–21 | 18.9–20 |
3–7 (metabolite) | |||||||
Elimination route | Kidney and liver | Mainly kidney | Mainly kidney | Mainly kidney | Mainly liver | Mainly kidney | Kidney and liver |
Renal (parent drug) | 63% (39%) | 87% (74%) | 85.4% (22.6%) | 74.9% (23.5%) | 5.5% (3.9%) | 75.6% (71.8%) | 45.4% (14.8%) |
Feces (parent drug) | 27% (11%) | 13% (10%) | 14.8% (4.5%) | 22.1% (21.6%) | 81.5% (74.1%) | 12.9% (11.4%) | 46.5% (26.1%) |
Dose reduction with RI (mild/moderate/severe) | No | Yes (100/50/25 mg) | Yes (50/50/50 mg) | Yes(5/2.5/2.5 mg) | No | Yes (25/12.5/6.25 mg) | No |
Dose reduction with HI (mild/moderate) | No | No | No | No | No | No | No |
Use with other drugs | - | - | - | Dose reduction with strong CYP3A4/5 inhibitors | - | - | - |
Parameter | Generic name (brand name) | ||||||
---|---|---|---|---|---|---|---|
Gemigliptin (Zemiglo) | Sitagliptin (Januvia) | Vildagliptin (Galvus) | Saxagliptin (Onglyza) | Linagliptin (Tragenta) | Alogliptin (Nesina) | Teneligliptin (Tenelia) | |
Monotherapy, short-term [35,37,41,42,43,44,45,46,47,48,49,50,51] | |||||||
Week | 12 | 18 | 24 | 12 | 18 | - | 12 |
Baseline HbA1c | 8.24 | 8.04 | 8.56 | 7.9 | 8.1 | - | 7.8 |
Change from baseline | –0.98 | –0.48 | –0.79 | –0.90 | –0.39 | - | –0.78 |
Monotherapy, long-term | |||||||
Week | 24 | 24 | 24 | 24 | 24 | 26 | 24 |
Baseline HbA1c | 8.66 | 8.01 | 8.38 | 8.0 | 8.0 | 7.9 | 7.63 |
Change from baseline | –1.24 | –0.61 | –0.72 | –0.5 | –0.44 | –0.6 | –0.90 |
Initial combination therapy with metformin [37,52,53,54,55,56] | |||||||
Week | 24 | 24 | 24 | 24 | 24 | 26 | - |
Baseline HbA1c | 8.65 | 8.79 | 8.7 | 9.4 | 8.7 | 8.4 | - |
Change from baseline | –2.06 | –1.90 | –1.8 | –2.5 | –1.6 | –1.6 | - |
Combination therapy: add-on to metformin [38,57,58,59,60,61,62] | |||||||
Week | 52 | 24 | 24 | 24 | 24 | 26 | 16 |
Baseline HbA1c | 7.89 | 7.96 | 8.38 | 8.1 | 8.09 | 7.9 | 7.79 |
Change from baseline | –1.06 | –0.67 | –0.88 | –0.7 | –0.49 | –0.6 | –0.87 |
Combination therapy: add-on to metformin and sulfonylurea [39,63,64,65,66] | |||||||
Week | 24 | 24 | 24 | 24 | 24 | - | - |
Baseline HbA1c | 8.12 | 8.27 | 8.75 | 8.4 | 8.15 | - | - |
Change from baseline | –0.88 | –0.59 | –1.01 | –0.74 | –0.72 | - | - |
Combination therapy: add-on to insulin [40,67,68,69,70,71] | |||||||
Week | 12a | 24 | 24 | 24 | 24 | 26 | - |
Baseline HbA1c | 8.41 | 8.7 | 8.8 | 8.7 | 8.3 | 9.3 | - |
Change from baseline | –0.95 | –0.6 | –0.8 | –0.7 | –0.6 | –0.7 | - |