Incretin-Based Therapy for Prevention of Diabetic Vascular Complications

Table 1

Clinical trials and animal studies of selected incretin-based agents for kidney disease.

Study (drug)	Numbers	Treatment plan	Outcome
Hattori [48]; (sitagliptin and alogliptin; 2014)	Sitagliptin and alogliptin; 12	Sitagliptin 50 mg/day for 4 weeks (first period; baseline), alogliptin 25 mg/day for 4 weeks (second period), and sitagliptin 50 mg/day for 4 weeks (third period)	Significant decreases in albuminuria after the change from sitagliptin to alogliptin (81.0 ± 52.4 to 33.9 ± 23.9 mg/g Cr; )
Frederich et al. (presentation abstract; American Diabetes Association 74th Scientific Sessions, 2014); Subanalysis study of SAVOR-TIMS53; (saxagliptin; 2013)	Saxagliptin, 2043; placebo, 799	Saxagliptin 2.5, 5, or 10 mg/day (24 weeks)	Significant increases in negative rate of albuminuria (4.6% versus 13.4%)
Groop et al. [53]; (linagliptin (MARLINA-T2D); ongoing)	A total of 350 eligible individuals are randomized in a 1 : 1 ratio to receive linagliptin or placebo	Linagliptin 5 mg/day for 24 weeks
Mima et al. [11]; (exendin-4)	STZ-induced diabetic mice + exendin-4; 6; STZ-induced diabetic mice + vehicle; 6	Exendin-4 (1.0 nmol/kg/day) was administrated intraperitoneally for 6 months	Significant decreases in albuminuria (by 27 ± 10%; ) and mesangial expansion (by 38 ± 10%; ) compared to DM + vehicle
Park et al. [54]; (exendin-4)	db/db mice + exendin-4; 8; db/db mice + vehicle; 8	Exendin-4 (1.0 nmol/kg/day) was administrated intraperitoneally for 8 weeks	Significant decreases in albuminuria (), mesangial matrix fraction (), and macrophages infiltration in glomeruli ()
Kodera et al. [55]; (exendin-4)	STZ-induced diabetic rats + exendin-4; 6; STZ-induced diabetic rats + vehicle; 6	Exendin-4 (10 g/kg/BW) was administrated intraperitoneally for 8 weeks	Significant decreases in albuminuria (), mesangial matrix expansion (), and ICAM-1 expression in glomeruli ()
Hendarto et al. [56]; (liraglutide)	STZ-induced diabetic rats + liraglutide; STZ-induced diabetic rats + vehicle	Liraglutide (0.3 mg/kg/12 h) was administrated with subcutaneous injection for 4 weeks	Significant decreases in albuminuria (), NOX4 in glomeruli (), and TGF- expression in glomeruli ()
Kanasaki et al. [57]; (linagliptin)	STZ-induced diabetic mice + linagliptin; 5-6; STZ-induced diabetic mice + vehicle; 7-8	Linagliptin (5 mg/kg BW/day) in drinking water for 4 weeks	Significant decreases in albuminuria () and mesangial matrix expansion ()

STZ, streptozotocin; BW, body weight; ICAM-1, intercellular adhesion molecule-1; TGF-, transforming growth factor-.