Antihypertensive effect for canagliflozin in diabetic renal disease
medwireNews: The sodium-glucose cotransporter (SGLT)2 inhibitor canagliflozin reduces blood pressure (BP) and the need for additional antihypertensives in people with type 2 diabetes and chronic kidney disease, research suggests.
The findings emerge from a post-hoc analysis of the CREDENCE trial and “build upon previous randomized studies that observed moderate reductions in BP with SGLT2 inhibition in people with [type 2 diabetes] and normal kidney function,” according to the investigators.
By the third week of treatment, the 2172 people randomly assigned to take canagliflozin had an average 3.39 mmHg reduction in systolic BP, compared with a 0.11 mmHg increase among the 2169 taking placebo. This difference persisted for the duration of follow-up, which continued for a median of 2.6 years, by which point the trial met the prespecified efficacy criteria for the primary renal outcome and was stopped early.
“Because CREDENCE recruited individuals at high risk of kidney disease progression, the burden of elevated BP was substantially higher than in previous trials,” write Brendon Neuen (The George Institute for Global Health, Sydney, New South Wales, Australia) and study co-authors in Circulation.
They say the size of BP reduction achieved with canagliflozin in CREDENCE is comparable to that produced by low-dose hydrochlorothiazide.
“Canagliflozin could be considered as an adjunct blood pressure lowering agent in addition to its kidney and cardiovascular protective effects,” says the team.
During the trial, 39.8% of the canagliflozin group and 61.3% of the placebo group required new BP-lowering medications, equating to a significant 32% reduced likelihood for this outcome in favor of canagliflozin.
The BP reduction obtained with canagliflozin accounted for less than 6% of its protective effect against any renal or cardiovascular endpoint, however.
BP reduction with canagliflozin was consistent in participants with and without resistant hypertension and across baseline systolic BP categories (ranging from <130 to ≥150 mmHg).
The researchers highlight this “important distinction” from existing antihypertensives, which have larger effects in people with higher baseline BP.
“For the most part, effects on BP have been attributed to natriuresis and osmotic diuresis, the premise of which is predicated on normal kidney function,” they say.
However, the team notes that participants of CREDENCE achieved similar BP reductions irrespective of whether they had “significant glycosuria,” suggesting “that natriuresis may not be the sole mechanism for BP lowering in this population.”
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