Figure 1: Chemical structures of Acarbose and miglitol

Figure 2: Chemical structures of AICAR and Metformin

Figure 3: Chemical structures of sulfonylureas

Figure 4: Chemical structures of PPARα agonists

Figure 5: Chemical structures of PPARγ agonists

Figure 6: Chemical structure of dipeptidyl peptidase IV (DP-4) inhibitors

Figure 7: Chemical structures of sodium glucose transporter-2 (SGLT-2) inhibitors

Figure 8: The overall hypoglycemic mechanisms of oral therapies mentioned in this article

residuea  

7 10   15   20   25   30   35   40

Exenatide:

HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS

GLP-1:

HAEGTFTSDVSSYLEGQAAKEFIAWLVKGR

Liraglutide:

HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG

Semaglutide:

HXEGTFTSDVSSYLEGQAAKEFIAWLVRGRG

a Because the leading sequence of GLP-1 is comprised of 6 residues that are cleaved off before secretion, circulating GLP-1 starts with residue 7
The 2nd residue of semaglutide is replaced by amino-isobutyric acid (2-methyl alanine)
Table 1:Peptide sequences of glucagon like peptide-1 (GLP-1)

Compound

Molecular weight
enzyme(s)

Bioavailability

Biological

Major clearance

(g/mol)

 

half-life

 

 

Metformin

129.16

55%

5 hr

CYP2C11, CYP3A1/2

Tolbutamide

270.35

34.1%

9.1 hr

CYP2C9

Glidbenclamide

494.00

60-95%

10 hr

CYP3A4

Glimepirid

492.63

100%

5-8 hr

CYP2C9

Clofibrate

242.07

95.99%

10 hr

Acyl CoA synthetase

Fenofibrate

360.83

58%

19-27 hr

UDP-glucuronosyl transferase

Troglitazone

441.54

40-50%

7.6-24hr ,

CYP2C8, CYP2C9

Rosiglitazone

357.43

95-99%

4-6 hr

CYP2C8, CYP2C9, CYP3A4

Sitagliptin

407.31

87%

8-14 hr

CYP3A4, CYP2C8

Vildagliptin

303.40

85%

2 hr

DP4

Saxogliptin

315.41

50%

27 hr

CYP3A4/5

Phlorizin

436.41

?

?

?

Dapagliflozin

408.87

78%

12.9 hr

UGT1A9

Canagliflozin

444.52

65%

10.6-13.1 hr

UGT1A9, UGT2B4

CYP: cytochrome P450 monooxygenase
DP4: dipeptidyl peptidase IV, Vildagliptin is degraded mainly by the enzyme it inhibits, dipeptidyl peptidase IV
UGT: UDP glucuronosyl transferase isozyme
Table 2:Pharmacokinetic properties of recent oral therapies for diabetes mellitus