Pleiotropic effects of liraglutide treatment on renal risk factors in type 2 diabetes: Individual effects of treatment.

AIMS/HYPOTHESIS: Management of diabetic nephropathy includes reduction of albuminuria, blood pressure and weight. The GLP-1 receptor agonist liraglutide may possess these pleiotropic effects in addition to the glucose lowering effect. We aimed to elucidate the individual liraglutide treatment response by determining if high responders (highest reduction) in each risk factor also had high response in other renal risk factors (cross-dependency).

METHODS: Open-label study: 31 type 2 diabetics treated with liraglutide for 7weeks. After 3weeks washout 23 re-started treatment and were followed for 1year. HbA1c , weight, systolic blood pressure (SBP), urinary albumin excretion rate (UAER) and mGFR (51 Cr-EDTA) were evaluated. Changes in high (Q4) vs. low responders (Q1-Q3) were compared for each renal risk factor. The effects of treatment/off treatment/re-treatment (off-on/off-on effect) were evaluated to account for random effects.

RESULTS: After 7weeks HbA1c was reduced 6(95% CI: 3;9)mmol/mol, weight 2.5(1.8;3.2)kg, SBP 4(-1;9)mmHg, UAER 30(12;44)% and mGFR 11(7;14)ml/min per 1.73m2 . mGFR high responders had a significant reduction in weight compared to low responders (4.3 vs. 1.9kg; p=0.002). SBP high responders had a tendency of a higher reduction in UAER compared to low responders (47 vs. 23%, p=0.14). No cross-dependency was observed in any of the other renal risk factors (p≥0.16). Treatment response did not differ after 7weeks and 1year (p≥0.12).

CONCLUSIONS/INTERPRETATION: Liraglutide possesses pleiotropic effects on renal risk factors. On patient level, effect on the individual risk factor cannot be anticipated based on response in other risk factors. Response when re-starting treatment did not differ, indicating that our primary findings were not random.