Incretin-Based Therapy for Prevention of Diabetic Vascular Complications

Table 2

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

Study (drug)	Patient numbers	Treatment plan	Outcome
Ku and  Su [58]; (sitagliptin; 2014)	Sitagliptin, 19; placebo 31	Sitagliptin (100 mg/day) was administrated for 4 weeks	Significant improvement in myocardial function and reduction in postischemic stunning (ejection fraction, 70.5 ± 7.0 versus 65.7 ± 8.0%; ; strain rate in ischemic segments, −2.27 ± 0.65 versus −1.988 ± 0.58 s^−1; )
Green et al. [59]; (sitagliptin (TECOS); 2015)	Sitagliptin, 839; placebo, 851 (primary outcome)	Sitagliptin 100 mg/day (or 50 mg/day if the baseline GFR was ≥30 and <50 mL per minute per 1.73 m^2); Median follow-up was 3.0 years	Sitagliptin was noninferior to placebo for the primary compositive cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; ). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; )
Pfeffer et al.; (presentation abstract; American Diabetes Association 75th Scientific Sessions, 2015 Lixisenatide (ELIXA); 2015)	Lixisenatide, 3034; placebo, 3034	Lixisenatide 10–20 g/day Median follow-up was 2.1 years	Lixisenatide was noninferior to placebo for the primary compositive cardiovascular outcome (hazard ratio, 0.97; 95% CI, 0.85 to 1.10). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 0.94; 95% CI, 0.78 to 1.13). Rates of mortality (hazard ratio, 0.94; 95% CI, 0.78 to 1.13)
Ye et al. [60]; (Sitagliptin)	Mice underwent coronary ligation + sitagliptin 10; mice underwent coronary ligation + vehicle 10	Sitagliptin (300 mg/kg/day) was administrated by oral gavage for 3 or 14 days	Significant decreases in infarct size (24.3 ± 0.7% in 3 days; and 16.9 ± 0.6%; in 14 days)
Gomez et al. [61]	Hybrid (landrace and large white) pigs with BNP; infusion + sitagliptin; 6; Placebo; 6	Sitagliptin (30 mg/kg/BW) was orally administrated for 3 weeks	An increase in stroke volume was observed in the sitagliptin group compared with placebo (+24 + 6% versus −17 + 7%, ). Glomerular filtration rate declined at week 4 compared; with baseline in the placebo group (1.3 + 0.4 versus 2.3 + 0.3 mL/kg/min, )
Takahashi et al. [62]	Mice underwent transverse aortic constriction + sitagliptin; 40; Mice underwent transverse aortic constriction + vehicle; 41	Vildagliptin (10 mg/kg/BW day) was administrated by drinking water	Improvement of both LV dilatation and dysfunction in the transverse aortic constriction group ameliorated ()

GFR, glomerular filtration rate; BW, body weight; BNP, brain natriuretic peptide.