insulin-glargine and empagliflozin

Type 2 diabetes causes cardio-renal complications and is treated with different combination therapies. The renal hemodynamics profile of such combination therapies has not been evaluated in detail.. Patients (N = 97) with type 2 diabetes were randomized to receive either empagliflozin and linagliptin (E+L group) or metformin and insulin glargine (M+I group) for 3 months. Renal hemodynamics were assessed with para-aminohippuric acid and inulin for renal plasma flow (RPF) and glomerular filtration rate (GFR). Intraglomerular hemodynamics were calculated according the Gomez´ model.. Treatment with E+L reduced GFR (p = 0.003), but RPF remained unchanged (p = 0.536). In contrast, M+I not only reduced GFR (p = 0.001), but also resulted in a significant reduction of RPF (p < 0.001). Renal vascular resistance (RVR) decreased with E+L treatment (p = 0.001) but increased with M+I treatment (p = 0.001). The changes in RPF and RVR were different between the two groups (both p. In patients with type 2 diabetes and preserved renal function treatment with M+I resulted in reduction of renal perfusion and increase in vascular resistance, in contrast to treatment with E+I that preserved renal perfusion and reduced vascular resistance. Moreover, different underlying effects on the resistance vessels have been estimated according to the Gomez model, with M+I increasing R. The study was registered at www.clinicaltrials.gov (NCT02752113) on April 26, 2016.

Topics: Aged; Benzhydryl Compounds; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Female; Germany; Glomerular Filtration Rate; Glucosides; Hemodynamics; Humans; Hypoglycemic Agents; Insulin Glargine; Linagliptin; Male; Metformin; Middle Aged; Prospective Studies; Renal Plasma Flow; Sodium-Glucose Transporter 2 Inhibitors; Time Factors; Treatment Outcome

Preserved vascular function represents a key prognostic factor in type 2 diabetes mellitus (T2DM), but data on vascular parameters in this patient cohort are scarce. Patients with T2DM often need more than one drug to achieve optimal glucose control. The aim of this study was to analyse the efficacy of two combination therapies on vascular function in subjects with T2DM.. This prospective, randomized study included 97 subjects with T2DM. Subjects were randomized to either the combination therapy empagliflozin (E) 10 mg with linagliptin (L) 5 mg once daily or metformin (M) 850 or 1000 mg twice daily with insulin glargine (I) once daily. At baseline and after 12 weeks, subjects had peripheral office and 24-h ambulatory blood pressure (BP) measurement and underwent vascular assessment by pulse wave analysis under office and ambulatory conditions. Office, 24-h ambulatory and central BP as well as pulse pressure (PP) decreased after 12 weeks of treatment with E + L, whereas no change was observed in M + I. There were greater decreases in 24-h ambulatory peripheral systolic (between-group difference: -5.2 ± 1.5 mmHg, P = 0.004), diastolic BP (-1.9 ± 1.0 mmHg, P = 0.036), and PP (-3.3 ± 1.0 mmHg, P = 0.007) in E + L than M + I. Central office systolic BP (-5.56 ± 1.9 mmHg, P = 0.009), forward pressure height of the pulse wave (-2.0 ± 0.9 mmHg, P = 0.028), 24-h ambulatory central systolic (-3.6 ± 1.4 mmHg, P = 0.045), diastolic BP (-1.95 ± 1.1 mmHg, P = 0.041), and 24-h pulse wave velocity (-0.14 ± 0.05m/s, P = 0.043) were reduced to a greater extent with E + L.. Beyond the effects on glycaemic control, the combination therapy of E + L significantly improved central BP and vascular function compared with the classic combination of M + I.. NCT02752113.

Topics: Aged; Arterial Pressure; Benzhydryl Compounds; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Female; Germany; Glucosides; Humans; Insulin Glargine; Linagliptin; Male; Metformin; Middle Aged; Prospective Studies; Sodium-Glucose Transporter 2 Inhibitors; Time Factors; Treatment Outcome; Vascular Stiffness

Topics: Adamantane; Benzhydryl Compounds; Blood Glucose; Diabetic Ketoacidosis; Dipeptides; Dipeptidyl-Peptidase IV Inhibitors; Female; Glucosides; Humans; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome

This open-label, prospective study evaluated the effectiveness and safety of empagliflozin as add-on therapy in inadequately controlled type 2 diabetes (T2D) patients (glycated haemoglobin [HbA1c], 7.5-12%) who were already using three other types of orally active antidiabetic agents. A total of 268 T2D patients were enrolled and divided into two groups, empagliflozin (EMPA 25 mg/d, n = 142) or insulin glargine (INS, n = 126), respectively. After the treatment period of 24 weeks, HbA1c and fasting plasma glucose (FPG) were significantly reduced (HbA1c, P = 0.004; FPG, P = 0.008, respectively) in the EMPA group compared to the INS group. Also, EMPA treatment evoked a significant reduction in body weight (P < 0.001) and systolic blood pressure (P = 0.017) compared to the INS group. Hypoglycaemic adverse events were significantly higher in the INS group compared to the EMPA group (P = 0.001). In conclusion, this study demonstrated that a regimen comprising four different orally active antidiabetic agents, including EMPA, was effective and safe as a therapeutic strategy for treating T2D patients for glycaemic control and improvement of other cardiovascular and metabolic indices.

Topics: Aged; Benzhydryl Compounds; Blood Glucose; Diabetes Mellitus, Type 2; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Middle Aged; Prospective Studies; Treatment Outcome

Topics: Benzhydryl Compounds; Biosimilar Pharmaceuticals; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus, Type 2; Glucosides; Humans; Hypoglycemic Agents; Insulin Glargine