Effects of Empagliflozin + Linagliptin vs Metformin + Insulin Glargine on Renal and Vascular Changes in Type 2 Diabetes

Summary

Diabetes mellitus is a wide-spread disease accompanied by strongly increased morbidity and mortality due to micro- and macrovascular complications. However, in studies with patients suffering from diabetes mellitus type 2 (DM 2), early changes and impairments in large and small blood vessels as well as organ damage (e. g. to the kidneys) have been only insufficiently investigated (1). The newest substance class in oral antidiabetics, i. e. SGLT-2-inhibitors (such as empagliflozin) cause an increased renal excretion of glucose. In addition, the concurrent increased sodium excretion brings about an improvement of vascular function and thus a decrease in blood pressure. In the EMP-REG-OUTCOME study (2), the cardiovascular mortality rate was significantly lower in the empagliflozin group (3.7% versus 5.9%; 38% relative RR) compared to placebo.For another new substance class, the dipeptidylpeptidase-4-inhibitors, a number of pleiotropic effects have been described (3). In one of our recently conducted trials, we could demonstrate a positive effect of linagliptin on renal an inflammatory parameters compared to placebo (4). Thus, the combination of both substance classes with regard to positive effects on micro- and macrocirculation, even though not sufficiently proven as yet, suggests itself. The therapy with metformin and long-acting insulin (BOT), as well as a twofold oral medication is possible according to the recommendations of the "Deutsche Diabetes Gesellschaft (DDG)" and the positional paper of the "American Diabetes Association (ADA)". Accordingly, the aim of the present paper is the analysis of the effects of a combined therapy with empagliflozin plus linagliptin compared to metformin plus insulin glargine on renal and vascular changes in type 2 diabetes mellitus.

Timeline

Start

2016-04

Primary completion

2018-11-07

Completion

2019-05

Publications

• Background Striepe K, Jumar A, Ott C, Karg MV, Schneider MP, Kannenkeril D, Schmieder RE. Effects of the Selective Sodium-Glucose Cotransporter 2 Inhibitor Empagliflozin on Vascular Function and Central Hemodynamics in Patients With Type 2 Diabetes Mellitus. Circulation. 2017 Sep 19;136(12):1167-1169. doi: 10.1161/CIRCULATIONAHA.117.029529. No abstract available.
• Gunes-Altan M, Bosch A, Striepe K, Bramlage P, Schiffer M, Schmieder RE, Kannenkeril D. Is GFR decline induced by SGLT2 inhibitor of clinical importance? Cardiovasc Diabetol. 2024 May 29;23(1):184. doi: 10.1186/s12933-024-02223-0.
• 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.
• Ott C, Jung S, Korn M, Kannenkeril D, Bosch A, Kolwelter J, Striepe K, Bramlage P, Schiffer M, Schmieder RE. Renal hemodynamic effects differ between antidiabetic combination strategies: randomized controlled clinical trial comparing empagliflozin/linagliptin with metformin/insulin glargine. Cardiovasc Diabetol. 2021 Sep 4;20(1):178. doi: 10.1186/s12933-021-01358-8.
• Jung S, Bosch A, Kannenkeril D, Karg MV, Striepe K, Bramlage P, Ott C, Schmieder RE. Combination of empagliflozin and linagliptin improves blood pressure and vascular function in type 2 diabetes. Eur Heart J Cardiovasc Pharmacother. 2020 Nov 1;6(6):364-371. doi: 10.1093/ehjcvp/pvz078.

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