A Comparative Study of Safety Outcomes of Sodium Glucose Cotransporter-2 Inhibitors and Loop Diuretics Among Diabetic Patients Using Real-world Data

Rahhal, Alaa; Najim, Mostafa; Abusweireh, Asad; Habra, Masa; Elgassim, Lenah; Ali, Mohammed Omer; Habib, Mhd Baraa; Tahtouh, Raad; Al-Awad, Mohammad; Aljundi, Amer; Mahfouz, Ahmed; Dabdoob, Wafer; Alyafei, Sumaya; Asaad, Nidal

doi:10.1016/j.cpcardiol.2021.100995

Cited by 7 publications

(12 citation statements)

References 18 publications

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“…Rahhal et al . (2021) found that patients treated with combined SGLT2-Is and loop diuretics had greater adverse effects related to volume depletion as compared to single-agent SGLT2-Is [ 25 ]. Milder et al .…”

Section: Discussionmentioning

confidence: 99%

Safety outcomes of sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes and other risk factors for cardiovascular disease: a systematic review and meta-analysis

Deshpande

Patel

Regmi

et al. 2023

Cardiovascular Endocrinology &Amp; Metabolism

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Introduction Sodium-glucose cotransporter-2 inhibitors (SGLT2-Is) have emerged as standard therapy for heart failure. We aim to assess the safety of SGLT2-Is in patients with a high risk of cardiovascular disease. Areas covered An electronic database search was conducted for randomized control trials comparing SGLT2-Is to placebo in patients with a high risk of cardiac disease or heart failure. Data were pooled for outcomes using random-effect models. The odds ratio (OR) and 95% confidence interval (CI) were used to compare eight safety outcomes between the two groups. The analysis included ten studies with 71 553 participants, among whom 39 053 received SGLT2-Is; 28 809 were male and 15 655 were female (mean age, 65.2 years). The mean follow-up period was 2.3 years with the range being 0.8–4.2 years. The SGLT2-Is group had a significant reduction in AKI (OR = 0.8;95% CI 0.74–0.90) and serious adverse effects (OR = 0.9; 95% CI 0.83–0.96) as compared to placebo. No difference was found in fracture (OR = 1.1; 95% CI 0.91–1.24), amputation (OR = 1.1; 95% CI 1.00–1.29), hypoglycemia (OR 0.98;95% CI 0.83–1.15), and UTI (OR = 1.1; 95% CI 1.00–1.22). In contrast, DKA (OR = 2.4; 95% CI 1.65–3.60) and volume depletion (OR = 1.2; 95% CI 1.07–1.41) were higher in SGLT2-Is group. Expert opinion/commentary The benefits of SLGT2-Is outweigh the risk of adverse events. They may reduce the risk of AKI but are associated with an increased risk of DKA and volume depletion. Further studies are warranted to monitor a wider range of safety outcomes of SGLT2-Is.

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Section: Discussionmentioning

confidence: 99%

Safety outcomes of sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes and other risk factors for cardiovascular disease: a systematic review and meta-analysis

Deshpande

Patel

Regmi

et al. 2023

Cardiovascular Endocrinology &Amp; Metabolism

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“…[18] This class of drug, when used in combination with diuretics and/or ACE inhibitors and angiotensin receptor blockers, caution should be exercised because SGLT2 inhibitors have been linked to an increased risk of acute renal injury, dehydration, and orthostatic hypotension, which can worsen the underlying cardiovascular condition. [16,34] In patients using a long-term combination of SGLT2 inhibitors and loop diuretics, regular monitoring of volume-depletion adverse events is warranted in the study conducted by Rahhal A et al, particularly at a daily dose of diuretics with an equivalent dose greater than 40 mg. [19]…”

Section: Dapagliflozin-antihypertenisve Combination: Possible Risk Fo...mentioning

confidence: 99%

“…Recent studies state that the combination of SGLT2 inhibitors with diuretics may not significantly deplete volume. [19] This claim is verified in the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) study conducted by McMurray JJ et al, where the group of patients prescribed with dapagliflozin (16.3%) experienced the primary composite outcome of hospitalisation or death from cardiovascular causes comparatively lesser than the placebo group (21.2%) [21] and the study conducted by Wu JH et al, produced data that provides compelling and beneficial evidence for anticipating benefits from the use of SGLT2 inhibitors in those with type 2 diabetes who are at high risk of cardiovascular events. [18] Based on the volume depletion results of SGLT2 inhibitors used in diabetes mellitus obtained from the study conducted by Jackson AM et al, the volume depletion may not be a clinically significant adverse outcome when SGLT2 inhibitors are used alone.…”

Section: Studies Supporting the Cardiovascular Benefits Of Dapagliflo...mentioning

confidence: 99%

A Review on The Use of Dapagliflozin in Cardiovascular Diseases

Shifnaz

Shabaraya

2023

Int J Res Rev

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Dapagliflozin is a sodium-glucose co-transporter 2 inhibitor (SGLT2), used in decreasing the blood sugar levels in Type 2 diabetes mellitus patients by boosting urine glucose excretion, which also reduces the incidence of major adverse cardiovascular events. The drug has a higher affinity for cardio-protection and is observed to have reduced the risk of cardiovascular events in clinical trials and benefited in the prevention of cardiovascular diseases. It is recommended especially in patients with pre-existing CV conditions such as hypertension or myocardial infarction due to its higher baseline risk, but the use of drug was cautioned in patients who take pioglitazone or loop diuretics for hypertensive diabetes as it is believed to cause further volume depletion, resulting in lower eGFR. Dapagliflozin is a crucial treatment choice for a variety of individuals despite of its advised risk and regardless of patient history of cardiovascular disease, as it improves glycaemic control, body weight, and blood pressure while lowering the risk of cardiovascular mortality. This study reviews the therapeutic efficacy and the effects of dapagliflozin in diabetic patients with coexisting cardiovascular conditions and also compares several recent publications to comprise the risk and benefits of the drug in cardiovascular events and its role in the prevention of cardiovascular diseases and their complications. Keywords: Dapagliflozin, sodium-glucose co-transporter 2 inhibitor (SGLT2), cardiovascular diseases.

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“…2 Real world studies in patients with diabetes have also suggested that concurrent SGLT2 inhibitor and loop diuretic use may promote volume depletion. 3 On the other hand, the CREDENCE, EMPA-REG OUTCOME, and DAPA-CKD trials did not demonstrate differences in volume depletion events with diuretic usage, 4 although EMPA-REG OUTCOME did report that combination diuretic use with SGLT2 inhibition was associated with a larger initial eGFR "dip" compared to those taking SGLT2 inhibition alone. 5 Interestingly, a post-hoc analysis from DAPA-CKD reported a lower risk of kidney injury with dapagliflozina benefit that was similar in diuretic users vs. non-users, which serves to re-emphasize the kidney safety of these therapies.…”

mentioning

confidence: 99%

“… 3 Real world studies in patients with diabetes have also suggested that concurrent SGLT2 inhibitor and loop diuretic use may promote volume depletion. 4 …”

mentioning

confidence: 99%

Prescribing SGLT2 Inhibitors in Patients With CKD: Expanding Indications and Practical Considerations

Yau¹,

Dharia²,

Alrowiyti³

et al. 2022

Kidney International Reports

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A Comparative Study of Safety Outcomes of Sodium Glucose Cotransporter-2 Inhibitors and Loop Diuretics Among Diabetic Patients Using Real-world Data

Cited by 7 publications

References 18 publications

Safety outcomes of sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes and other risk factors for cardiovascular disease: a systematic review and meta-analysis

Safety outcomes of sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes and other risk factors for cardiovascular disease: a systematic review and meta-analysis

A Review on The Use of Dapagliflozin in Cardiovascular Diseases

Prescribing SGLT2 Inhibitors in Patients With CKD: Expanding Indications and Practical Considerations

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