Empagliflozin 10mg / Linagliptin 5mg tablets

BACKGROUND: Sodium-glucose cotransporter (SGLT) 2 inhibitors attenuate fasting glomerular hyperfiltration in people with type 2 diabetes (T2D). However, SGLT2-inhibition increases glucagon levels, which facilitate postprandial hyperfiltration. The impact of SGLT2 inhibition on protein-related hyperfiltration and postprandial (intra) kidney haemodynamic function is unclear. Moreover, the interaction with dipeptidyl-peptidase (DPP)-4 inhibitors, known to reduce glucagon levels and to affect meal-related factors modulating GFR, is unknown. AIMS: We aimed to assess the effects of empagliflozin and linagliptin in mono- and combination therapy compared to the initiation and intensification of SU-derivative gliclazide treatment on fasting and postprandial kidney haemodynamic function. MATERIALS AND METHODS: We compared three 16-week glucose-lowering strategies added to ongoing metformin monotherapy: (1) EMPA-LINA: 8-week empagliflozin 10 mg QD (EMPA0-8w) followed by the addition of 8-week linagliptin 5 mg QD (LINA8-16w); (2) LINA-EMPA: 8-week linagliptin (LINA0-8w) followed by the addition of 8-week empagliflozin (EMPA8-16w) versus (3) GLIC-GLIC: 8-week gliclazide 30 mg QD (GLIC0-8w) followed by the addition of 8-week gliclazide 30 mg (GLIC8-16w). We studied (intra) kidney haemodynamic interactions of this combination using iohexol and PAH clearance techniques to assess measured glomerular filtration rate (mGFR) and effective renal plasma flow (ERPF). RESULTS: and urinary albumin-creatinine-ratio 1.0 [0.4-1.9] mg/mmol). In the fasting state, EMPA0-8w (-13.2; -21.3 to -5.1 mL/min) but not LINA0-8w reduced within-group mGFR. EMPA8-16w (-10.2; -16.5 to -4.0 mL/min) but not LINA8-16w reduced within-group mGFR. Following a proteinload, EMPA0-8w (-11.4; -20.2 to -2.6 mL/min) and EMPA8-16w (-16.2; -22.9 to -9.4 mL/min) but not LINA0-8w or LINA8-16w reduced within-group mGFR. Versus the comparatorarm, fasting mGFR EMPA0-8w, EMPA8-16w and EMPA-LINA and postprandial mGFR EMPA8-16w and LINA-EMPA, were significantly reduced. mGFR reductions resulted from intrakidney efferent vasodilation rather than afferent vasoconstriction. CONCLUSION: In T2D people without CKD, the favourable kidney haemodynamic effects of empagliflozin persist in the postprandial state and are irrespective of concurrent use of linagliptin.

Abstract licence: CC BY-NC-ND

Abstract Background Extensive literature review revealed that no RP–LC method has been developed for simultaneous estimation of EMPA, LINA and MET in combined dosage form. This is a newer combination approved by USFDA on 4th June 2019 and it is launch in the United State Market on 27th January 2020. Result A simple, sensitive, specific, precise and accurate reverse phase—high performance liquid chromatography (RP- HPLC) method has been developed for simultaneous estimation of Empagliflozin, Linagliptin and Metformin HCl in bulk and synthetic mixture. Phenomenex C 18 column (250 mm × 4.6 mm, 5 µm) was used as stationary phase for chromatographic separation through isocratic elution using Acetonitrile: Methanol: Water in a ratio (27: 20: 53, v/v/v) pH 4 adjusted with 1% Ortho-phosphoric acid as mobile phase at flow rate 1 ml/min. PDA detector was used for simultaneous analysis of all three drugs at common wavelength 223 nm and the each injection volume was 20 µl. The linearity range for Empagliflozin, Linagliptin and Metformin HCl was found to be 0.5–5 µg/ml, 0.25–2.5 µg/ml, and 50–500 µg/ml, respectively. The retention time for Empagliflozin, Linagliptin and Metformin HCl was found to be 14.5 min, 3.4 min and 2.01 min, respectively. The percentage (%) recovery was found to be 99.98–100.81% for Empagliflozin, 99.33–100.57% for Linagliptin and 100.65–101.35% for Metformin HCl respectively. Conclusion As per the international Conference on Harmonisation (ICH) Q2 (R1) guideline, proposed RP–LC method validation has been carried out. The proposed RP–LC method was repeatable and selective as per statistical analysis and it can be use for simultaneous estimation of Empagliflozin, Linagliptin and Metformin HCl in bulk and synthetic mixture. The proposed method might be applied for simultaneous estimation of all three drugs in pharmaceutical formulation.

Abstract licence: CC BY