Does SGLT2 inhibition with dapagliflozin overcome individual therapy resistance to RAAS inhibition?
Individual patients show a large variation in their response to renin-angiotensin-aldosteron system (RAAS) inhibition (RAASi), both in surrogates such as albuminuria and in hard renal outcomes. Sodium-glucose co-transporter 2 inhibitors (SGLT2) have been shown to lower albuminuria and to confer cardiovascular and, possibly, renal protection. To establish whether individual therapy resistance to RAASi can be overcome by adding an SGLT2 inhibitor, we assessed individual albuminuria responses in patients exposed to both RAASi and the SGLT2 inhibitor dapagliflozin. We used data from a randomized controlled cross-over trial designed to assess the albuminuria-lowering effect of 6-week treatment with dapagliflozin 10 mg/d. We extracted from the electronic medical records data on the albuminuria response upon initiation of RAASi before the trial period, and analysed individual albuminuria responses to RAASi and to dapagliflozin. We retrieved data on RAASi for 26 patients (age, 62 years [SD, 8]; female gender, 6 [23%]; 24-hour urinary albumin excretion, 521 [187-921] mg/24 h). The mean albuminuria-lowering response to RAASi was 26.5% (range, -76.1% to 135.1%). The addition of dapagliflozin res in a further reduction of 34.9%, (range, -83.9 to 94.2). Interestingly, the albuminuria response to RAASi significantly correlated with the response to dapagliflozin (Pearson correlation coefficient, 0.635 [95% CI, 0.328-0.821]; P < .001), indicating that patients who did not respond to RAASi also did not respond to dapagliflozin. We concluded that individual therapy resistance to RAASi cannot be overcome with the addition of a completely different class of drugs, SGLT2 inhibitors. These data suggest that the individual drug response is an intrinsic individual characteristic, possibly unrelated to the type of intervention, unless the mode of action of dapagliflozin on albuminuria is through the RAAS.
['Petrykiv|Sergei|S|', 'Laverman|Gozewijn D|GD|', 'de Zeeuw|Dick|D|', 'Heerspink|Hiddo J L|HJL|0000-0002-3126-3730']
D000368:Aged D000806:Angiotensin-Converting Enzyme Inhibitors D001559:Benzhydryl Compounds D015415:Biomarkers D018592:Cross-Over Studies D003924:Diabetes Mellitus, Type 2 D003928:Diabetic Nephropathies D018450:Disease Progression D004351:Drug Resistance D005260:Female D005960:Glucosides D006801:Humans D006943:Hyperglycemia D007003:Hypoglycemia D007004:Hypoglycemic Agents D007668:Kidney D008297:Male D049990:Membrane Transport Modulators D008875:Middle Aged D016032:Randomized Controlled Trials as Topic D051437:Renal Insufficiency D012084:Renin-Angiotensin System D012189:Retrospective Studies D051297:Sodium-Glucose Transporter 2 D000077203:Sodium-Glucose Transporter 2 Inhibitors
dapagliflozin albuminuria sodium-glucose co-transporter 2 inhibitor ACEi ARB personalized medicine type 2 diabetes