Table 2.
Details of approved drugs targeting the GLP-1 axis
| Target
|
GLP-1R agonist
|
DPP-4 inhibitor
|
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Generic name | Exenatide97,98 | Exenatide (extended-release)97,99 | Liraglutide100 | Lixisenatide101 | Alogliptin102 | Linagliptin103,105 | Saxagliptin105,106 | Sitagliptin107,108 | Vildagliptin109 | Anagliptin110 | Teneligliptin111 | Gemigliptin112–114 |
| Trade name | Byetta® | Bydureon® | Victoza® | Lyxumia® | Nesina® | Trajenta® | Onglyza® | Januvia® | Galvus® | Suiny® | Tenelia® | Zemiglo® |
| Route of administration | Subcutaneous injection twice daily | Subcutaneous injection once weekly | Subcutaneous injection once daily | Subcutaneous injection once daily | Oral | Oral | Oral | Oral | Oral | Oral | Oral | Oral |
| Dose/day | 10 μg | 2 mg exenatide once weekly | 0.6 mg | 20 μg | 25 mg | 5 mg | 5 mg | 100 mg | 200 mg | 100 mg | 20 mg | 50 mg |
| Cmax | 211 pg/mL | Multiphasic release over an approximately 10-week period | 35 ng/mL | 56.7 pg/mL | 145.5 ng/mL | 9.55 nM | 24 ng/mL | 950 nM | 1,223 ng/mL | 476 ng/mL | 176.50 ng/mL | 43.5 ng/mL |
| tmax (hours) | 2.1 | ND | 8–12 | 1–3.5 | 1.25 | 1.5 | 2 | 1–4 | 1.5 | 1.8 | 1 | 4.5 |
| t1/2 (hours) | 2.4 | 2.4 | 13 | 1.5–4.5 | 21 | 12 | 2.5 | 12.4 | 2.96 | 4.37 | 26.1 | 30.8 |
| Vd | 28.3 L | 28.3 L | 11–17 L | 90–140 L | 417 L | 1,110 L | 123 L | 198 L | 71 L | 2,470 (mL/kg) | ND | ND |
| CL/F | 9.1 L/hour | 9.1 (L/hour) | 1.2 (L/hour) | 20–67 L/hour | 10.43 L/hour | ND | ND | ND | 44.96 (L/hour) | 620 (mL/hour/kg) | 12.2 (L/hour) | ND |
| AUC0–24/∞ | 1,036 pg · hour/mL (AUC0–∞) | ND | 960 ng · hour/mL (AUC0–∞) | ND | 1,058 ng · hour/mL (AUC0–24h) | ND | 78 ng · hour/mL (AUC0–∞) | 8.52 μM · hour | 4,588 ng · hour/mL (AUC0–∞) | 2,110 ng · hour/mL (AUC0–∞) | 1,772.7 ng · hour/mL (AUC0–∞) | 503 ng · hour/mL (AUC0–24h) |
| PPB (%) | ND | ND | >98 | 55 | 20 | 75%–99% (concentration-dependent) | Negligible | 38 | 9.3 | 37.1–48.2 (10–100,000 ng/mL) | <80 | Not extensively bound |
| Adverse effects |
Common (>1%) GI, injection site hematoma, URTI, dizziness gastroenteritis, NP Rare (<0.1%) Angioedema, skin disorders, alopecia, somnolence, Pancreatitis115 |
Common (>1%) GI, NP, headache, injection site pruritus Rare (<0.1%) Angioedema, skin disorders, alopecia, somnolence Pancreatitis115 |
Common (>1%) GI, headache, anti-liraglutide antibody formation Rare (<0.1%) Unknown* Pancreatitis115 |
Common (>1%) GI, influenza, URTI, UTI, viral infection, dizziness, somnolence, back pain, injection site pruritus Rare (<0.1%) Unknown* Pancreatitis115 |
Common (>1%) Headache, diarrhea, pruritus, myalgia Rare (<0.1%) Hepatic dysfunction Pancreatitis115 |
Common (>1%) NP Rare (<0.1%) Unknown* Pancreatitis115 |
Common (>1%) Headache URTI, UTI Rare (<0.1%) Unknown* Pancreatitis115 |
Common (>1%) NP, URTI Rare (<0.1%) Unknown* Pancreatitis115 |
Common (>1%) NP, headache, dizziness, back pain, diarrhea Rare (<0.1%) Angioedema, elevated liver enzymes, hepatitis Pancreatitis115 |
Information is too limited to characterize the incidence of adverse events Pancreatitis115 |
Common (>1%) GI disorder, skin disorder, NP Rare (<0.1%) Unknown* Pancreatitis115 |
(In 7% of study group) Constipation, NP, URTI, increase in blood CPK, hypoglycemia and rash Rare (<0.1%) Unknown* Pancreatitis115 |
Notes: Terminal half-life is the time required for the plasma concentration of a drug to decrease 50% in the final stage of its elimination. GI effects may include nausea, vomiting, diarrhea, constipation, and dyspepsia. Unknown*, cannot be estimated from available data. Byetta®; Amylin Pharmaceuticals, LLC, San Diego, CA, USA, and AstraZeneca Pharmaceuticals LP, Wilmington, DE, USA; Bydureon®; Amylin Pharmaceuticals, LLC, San Diego, CA, USA, and AstraZeneca Pharmaceuticals LP, Wilmington, DE, US; Victoza®; Novo Nordisk, Princeton, NJ, USA; Lyxumia®; Sanofi, Paris, France; Nesina®; Takeda Pharmaceutical Company, Chūō-ku, Osaka, Japan; Trajenta®; Boehringer Ingelheim Pty Limited, Ingelheim am Rhein, Germany; Onglyza®; Bristol-Myers Squibb, Manhattan, New York City, USA; Januvia®; Whitehouse Station, NJ, USA; Galvus®; Novartis International AG, Basel, Basel-Stadt, Switzerland; Suiny®; Sanwa Kagaku Kenkyusho Co., Ltd., Nagoya, Aichi, Japan; Tenelia®; Mitsubishi Tanabe Pharma Corporation, Chūō-ku, Osaka, Japan, and Daiichi Sankyo Co., Ltd., Chūōō-ku, Tokyo, Japan; Zemiglo®; LG Life Sciences, Seoul, Korea.
Abbreviations: AUC, area under the curve; Cmax, mean peak concentration; tmax, time to reach mean peak concentration; t1/2, half-life; Vd, mean apparent volume of distribution; CL/F, apparent clearance; AUC0–t, area under the curve; PPB, plasma protein binding (% bound); GI, gastrointestinal; NP, nasopharyngitis; URTI, upper respiratory tract infection; UTI, urinary tract infection; CPK, creatine phosphokinase; ND, not defined; GLP-1, glucagon-like peptide-1; GLP-1R, GLP-1 receptor; DPP-4, diaminopeptidyl peptidase IV.