Hypertension is a leading modifiable risk factor for cardiovascular disease and premature death worldwide. Management of blood pressure (BP) is particularly challenging in patients with comorbid conditions such as type 2 diabetes (T2D), chronic kidney disease (CKD), or heart failure (HF). Sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) have become integral to modern cardiorenal therapy, and among these agents, dapagliflozin has consistently demonstrated additional BP-lowering effects in multiple clinical contexts. This narrative review synthesizes available clinical evidence on the antihypertensive effects of dapagliflozin and summarizes proposed biological mechanisms that may underlie these effects.
Clinical studies compiled in the review show that dapagliflozin produces measurable reductions in both systolic and diastolic BP. Across the described clinical settings, reductions in systolic BP (SBP) generally exceed reductions in diastolic BP (DBP). The magnitude of BP lowering varies by study population and comorbidities; the source emphasizes consistent antihypertensive signals rather than a specific single-effect size. The authors present dapagliflozin as a therapeutic agent that provides additional BP-lowering benefits in patients who have hypertension together with T2D, CKD, or HF.
The review summarizes several plausible biological mechanisms that may contribute to dapagliflozin’s antihypertensive effects:
Osmotic diuresis and natriuresis: By inhibiting renal SGLT2-mediated glucose reabsorption, dapagliflozin increases urinary glucose and water excretion, which can reduce plasma volume and lower BP.
Weight reduction: Modest weight loss observed with SGLT2 inhibitor therapy may contribute to reductions in BP.
Modulation of the sympathetic nervous system: The review notes potential effects on sympathetic activity as one mechanism, though detailed mechanistic pathways are not fully delineated in the source.
Enhanced uric acid excretion: Increased uricosuria associated with SGLT2 inhibition may play a role in vascular and BP benefits.
Attenuation of oxidative stress, inflammation, and vascular dysfunction: Anti-inflammatory and vasculoprotective effects are suggested as contributors to improved vascular function and lower BP.
The source treats these mechanisms as complementary and potentially synergistic, and indicates that the precise relative contribution of each mechanism remains incompletely defined.
Across clinical studies reviewed, reductions in SBP are reported to exceed reductions in DBP. The authors acknowledge that the physiological basis for this differential effect is not fully understood and that further investigation is needed to clarify why systolic pressure tends to respond more than diastolic pressure to dapagliflozin therapy.
Dapagliflozin has demonstrated generally good tolerability in clinical applications. The review highlights genital infections as a notable long-term safety consideration that may limit extended use in some patients. No other specific adverse event rates or comparative safety statistics are reported in the source. The review frames the infection risk as an important clinical consideration when weighing dapagliflozin’s antihypertensive and cardiorenal benefits.
The authors conclude that current evidence supports dapagliflozin as a cardiorenal therapeutic agent that may provide additional BP-lowering benefits in patients with hypertension who also have T2D, CKD, or HF. Importantly, the review emphasizes that dapagliflozin should be viewed as complementary to, rather than a substitute for, conventional antihypertensive therapy. The source calls attention to remaining evidence gaps: long-term hypertension-focused clinical studies are needed to better define its role specifically for hypertension management, to quantify BP effects across diverse hypertensive populations, and to determine optimal integration with standard antihypertensive regimens.
In summary, dapagliflozin — an SGLT2 inhibitor — produces consistent but variable BP-lowering effects, with greater reductions typically observed in systolic than diastolic pressure. Multiple mechanisms likely account for these effects, including osmotic diuresis and natriuresis, weight loss, sympathetic modulation, increased uric acid excretion, and mitigation of oxidative stress, inflammation, and vascular dysfunction. While the agent demonstrates good tolerability overall, the risk of genital infections remains a clinical limitation. The review recommends further hypertension-focused randomized trials to clarify dapagliflozin’s specific role in hypertension treatment, optimal patient selection, and long-term benefit–risk balance.
Note: The source is a narrative review and does not provide granular numerical effect sizes, head-to-head trial results for hypertension as a primary outcome, or detailed adverse event incidence rates within this abstract; those specifics were not reported in the provided source text.