Effects of Saxagliptin on Endothelial Function

Summary

Diabetes mellitus is a metabolic disease with a growing prevalence worldwide. Currently available therapies for type 2 diabetes have various limitations and are associated with increased risk of hypoglycemia, weight gain, gastrointestinal side effects or edema and heart failure. A new and promising class of drugs are the gliptins. Several efficacy studies demonstrated a significant improvement of HbA1c with gliptins. In addition, gliptins improved fasting as well as prandial glucose levels and did not induce weight gain. Due to these positive metabolic effects in combination with a very small spectrum of side effects gliptins might very well be part of the standard therapy for type 2 diabetes in the future. Apart form surrogate parameters like reduction of fasting and postprandial blood glucose levels or improvement of HbA1c, the effect of gliptins on micro- and macrovascular function and cardiovascular outcome has not been the primary focus of current studies. Diabetes mellitus is strongly associated with microangiopathy and macroangiopathy and is a strong independent risk factor for cardiovascular disease and cardiovascular mortality. Endothelial dysfunction which plays a crucial role in the atherosclerotic process is commonly observed in patients with diabetes mellitus and already prediabetes and has - amongst other factors - been linked to fasting and postprandial hyperglycemia. Taken into account that gliptins reduce hyperglycemia and hyperglycemic peaks by preventing inactivation of GLP-1, which exerted beneficial effects on the endothelium in previous studies it is of major interest whether therapy with gliptins improves endothelial function.

Timeline

Start

2010-10

Primary completion

2013-04

Completion

2013-04

Publications

• Results Ott C, Raff U, Schmidt S, Kistner I, Friedrich S, Bramlage P, Harazny JM, Schmieder RE. Effects of saxagliptin on early microvascular changes in patients with type 2 diabetes. Cardiovasc Diabetol. 2014 Jan 14;13:19. doi: 10.1186/1475-2840-13-19.
• Staef M, Ott C, Kannenkeril D, Striepe K, Schiffer M, Schmieder RE, Bosch A. Determinants of arterial stiffness in patients with type 2 diabetes mellitus: a cross sectional analysis. Sci Rep. 2023 Jun 2;13(1):8944. doi: 10.1038/s41598-023-35589-4.
• Kannenkeril D, Bosch A, Harazny J, Karg M, Jung S, Ott C, Schmieder RE. Early vascular parameters in the micro- and macrocirculation in type 2 diabetes. Cardiovasc Diabetol. 2018 Sep 19;17(1):128. doi: 10.1186/s12933-018-0770-4.

Drugs

Indications