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Evaluating the effects of sodium glucose co-transporter -2 inhibitors from a renin-angiotensin-aldosterone system perspective in patients infected with COVID-19: contextualizing findings from the dapagliflozin in respiratory failure in patients with COVID-19 study.
Moustafa, DA, Imran, Z, Ismail, R, Rayan, M, Gadeau, AP, Eldassouki, H, Abdulrahman, N, Mraiche, F
Molecular biology reports. 2022;(3):2321-2324
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Abstract
Numerous studies demonstrate parallels between CVD, type 2 diabetes mellitus (T2DM) and COVID-19 pathology, which accentuate pre-existing complications in patients infected with COVID-19 and potentially exacerbate the infection course. Antidiabetic drugs such as sodium-glucose transporter-2 (SGLT-2) inhibitors have garnered substantial attention recently due to their efficacy in reducing the severity of cardiorenal disease. The effect of SGLT-2 inhibitors in patients with COVID-19 remains unclear particularly since SGLT-2 inhibitors contribute to altering the RAAS cascade activity, which includes ACE-2, the major cell entry receptor for SARS-CoV2. A study, DARE-19, was carried out to unveil the effects of SGLT-2 inhibitor treatment on comorbid disease complications and concomitant COVID-19 outcomes and demonstrated no statistical significance. However, the need for further studies is essential to provide conclusive clinical findings.
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Paeoniflorin: A neuroprotective monoterpenoid glycoside with promising anti-depressive properties.
Wang, XL, Feng, ST, Wang, YT, Chen, NH, Wang, ZZ, Zhang, Y
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2021;:153669
Abstract
BACKGROUND Depression, as a prevalent and debilitating psychiatric disease, severely decreases the life quality of individuals and brings heavy burdens to the whole society. Currently, some antidepressants are applied in the treatment of severe depressive symptoms, while there are still some undesirable drawbacks. Paeoniflorin is a monoterpenoid glycoside that was firstly extracted from Paeonia lactiflora Pall, a traditional Chinese herb that is widely used in the Chinese herbal formulas for treating depression. PURPOSE This review summarized the previous pre-clinical studies of paeoniflorin in treating depression and further discussed the potential anti-depressive mechanisms for that paeoniflorin to be further explored and utilized in the treatment of depression clinically. METHODS Some electronic databases, e.g., PubMed and China National Knowledge Infrastructure, were searched from inception until April 2021. RESULTS This review summarized the effective anti-depressive properties of paeoniflorin, which is related to its functions in the upregulation of the levels of monoaminergic neurotransmitters, inhibition of the hypothalamic-pituitary-adrenal axis hyperfunction, promotion of neuroprotection, promotion of hippocampus neurogenesis, and upregulation of brain-derived neurotrophic factor level, inhibition of inflammatory reaction, downregulation of nitric oxide level, etc. CONCLUSION This review focused on the pre-clinical studies of paeoniflorin in depression and summarized the recent development of the anti-depressive mechanisms of paeoniflorin, which approves the role of paeoniflorin plays in anti-depression. However, more high-quality pre-clinical and clinical studies are expected to be conducted in the future.
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Low carbohydrate diet while taking dapagliflozin: A case report and review of literature.
Paul, N, Jonklaas, J
Diabetes & metabolic syndrome. 2021;(1):361-363
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Sodium-Glucose Cotransporter Inhibitors in Non- Diabetic Heart Failure: A Narrative Review.
Dahal, R, Acharya, Y, Mukherjee, D
Cardiovascular & hematological disorders drug targets. 2021;(1):1-6
Abstract
BACKGROUND Heart failure (HF) is one of the leading public health problems with a substantial burden in the global healthcare system. Although significant efforts are based on prevention, early recognition, and proper management of HF, the worldwide surge of risk factors like hypertension, diabetes, and obesity has further complicated the existing problem. OBJECTIVE This study aims to define the role of the sodium-glucose cotransporter 2 (SGLT2) inhibitors in non-diabetic HF. METHODS We performed a comprehensive literature review to examine the available evidence in the clinical implications of SGLT2 inhibitors in non-diabetic HF using the online databases (PubMed and Embase). RESULTS We identified two RCTs-DAPA-HF and DEFINE-HF, which were conducted to analyze the net clinical benefit of dapagliflozin in non-diabetic HF patients. Although we could not study the composite effects of these studies due to the difference in outcome measures, the individual outcomes look promising. The number needed to treat (NNT) to prevent one primary event was 21 (95% CI: 15 to 38) in the DAPA study. In DEFINE HF study, responder analysis showed a significant proportion of patients in the treatment arm experienced improvements in the functional status with clinically meaningful improvement in KCCQ-OS by 3.7 points and KCCQ-CS by 4.6 points with NNT of 10 and 7, respectively, at 12 weeks. Both studies also showed low safety concerns in patients without T2D. CONCLUSION The outcomes of the two RCTs, DAPA-HF and DEFINE-HF, that studied the effects of SGLT2 inhibitors in non-diabetic HF showed promising clinical outcomes. Although we are waiting for other prospective RCTs to reflect similar results and safety profiles, it seems the SGLT2 inhibitors can have broader clinical implications in managing non-diabetic HF with improved cardiovascular outcomes.
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Severe euglycemic diabetic ketoacidosis of multifactorial etiology in a type 2 diabetic patient treated with empagliflozin: case report and literature review.
Sampani, E, Sarafidis, P, Dimitriadis, C, Kasimatis, E, Daikidou, D, Bantis, K, Papanikolaou, A, Papagianni, A
BMC nephrology. 2020;(1):276
Abstract
BACKGROUND Sodium-glucose co-transporter-2 (SGLT-2) inhibitors are a relatively novel class of oral medications for the treatment of Type 2 DM with a generally acceptable safety profile. However, these agents have been associated with rare events of a serious and potentially life-threatening complication named euglycemic diabetic ketoacidosis (euDKA). euDKA is not identical with the typical diabetic ketoacidosis, as it often presents with serious metabolic acidosis but only mild to moderate glucose and anion gap elevation. CASE PRESENTATION We report a case of a 51-year old female with Type 2 DM treated with an SGLT-2 inhibitor, developing severe metabolic acidosis with only mild blood glucose elevation after a routine surgery. A careful evaluation of involved factors led to the diagnosis of euDKA, followed by cautious application of simple therapeutic measures that resulted in complete restoration of acidosis and glycemic control in less than 48-h. CONCLUSIONS Euglycemic ketoacidosis is a rare but rather serious complication of SGLT-2 inhibitors use, often with a multifactorial etiology. Its atypical presentation requires a high level of awareness by physicians as early recognition of this complication can quickly and safely restore acid-base balance.
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Glucagon-Like Peptide 1 Receptor Agonists and Heart Failure: The Need for Further Evidence Generation and Practice Guidelines Optimization.
Khan, MS, Fonarow, GC, McGuire, DK, Hernandez, AF, Vaduganathan, M, Rosenstock, J, Handelsman, Y, Verma, S, Anker, SD, McMurray, JJV, et al
Circulation. 2020;(12):1205-1218
Abstract
With worsening epidemiological trends for both the incidence and prevalence of type 2 diabetes mellitus (T2DM) and heart failure (HF) worldwide, it is critical to implement optimal prevention and treatment strategies for patients with these comorbidities, either alone or concomitantly. Several guidelines and consensus statements have recommended glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter type 2 inhibitors as add-ons to lifestyle interventions with or without metformin in those at high atherosclerotic cardiovascular disease risk. However, these recommendations are either silent about HF or fail to differentiate between the prevention of HF in those at risk versus the treatment of individuals with manifest HF. Furthermore, these documents do not differentiate among those with different HF phenotypes. This distinction, even though important, may not be critical for sodium-glucose cotransporter type 2 inhibitors in view of the consistent data for benefit for both atherosclerotic cardiovascular disease- and HF-related outcomes that have emerged from the regulatory-mandated cardiovascular outcome trials for all sodium-glucose cotransporter type 2 inhibitors and the recent DAPA-HF trial (Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction)demonstrating the benefit of dapagliflozin on HF-related outcomes in patients with HF with reduced ejection fraction with or without T2DM. However, the distinction may be crucial for glucagon-like peptide-1 receptor agonists and other antihyperglycemic agents. Indeed, in several of the new statements, glucagon-like peptide-1 receptor agonists are suggested treatment not only for patients with T2DM and atherosclerotic cardiovascular disease, but also in those with manifest HF, despite a lack of evidence for the latter recommendation. Although glucagon-like peptide-1 receptor agonists may be appropriate to use in patients at risk for HF, mechanistic insights and observations from randomized trials suggest no clear benefit on HF-related outcomes and even uncertainty regarding the safety in those with HF with reduced ejection fraction. Conversely, theoretical rationales suggest that these agents may benefit patients with HF with preserved ejection fraction. Considering that millions of patients with T2DM have HF, these concerns have public health implications that necessitate the thoughtful use of these therapies. Achieving this aim will require dedicated trials with these drugs in both patients who have HF with reduced ejection fraction and HF with preserved ejection fraction with T2DM to assess their efficacy, safety, and risk-benefit profile.
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Fournier's gangrene and SGLT2 inhibitors: A case study.
García-García, A, Galeano-Valle, F, Nuevo-González, JA, Demelo-Rodríguez, P
Endocrinologia, diabetes y nutricion. 2020;(6):423-425
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Dapagliflozin and cardiovascular outcomes in patients with Type 2 diabetes.
Al-Bazz, DY, Wilding, JP
Future cardiology. 2020;(2):77-88
Abstract
The relationship between cardiovascular disease, heart failure (HF) and Type-2 diabetes (T2DM) is widely recognized. Cardiovascular (CV) outcome trials are required for all new glucose-lowering agents to confirm safety with respect to CV risk. CV outcome trials with SGLT2i inhibitors have shown CV benefit, with reductions in major CV events and HF. This review focuses on the DECLARE-TIMI 58 trial with dapagliflozin in T2DM, which showed noninferiority for major adverse cardiovascular events and reduction in hospitalization for HF and associated CV mortality in a broad range of patients with T2DM. The DAPA-HF trial of dapagliflozin in people with HF with reduced ejection fraction with and without T2DM confirms benefits for those with HF.
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United States Pharmacopeia Safety Review of Willow Bark.
Oketch-Rabah, HA, Marles, RJ, Jordan, SA, Low Dog, T
Planta medica. 2019;(16):1192-1202
Abstract
Willow bark (Salix spp.) is an ingredient in some dietary supplements. No serious adverse effects were reported from trials of willow bark extracts delivering 120 - 240 mg salicin (the purported active constituent) daily for up to 8 weeks. All studies involved adults only; none involved special subpopulations such as pregnant or breastfeeding women, or children. The most common adverse effects associated with willow bark are gastrointestinal; a few allergic reactions were also reported. Some publications advise caution when taking willow bark. There is a risk of increased bleeding in vulnerable individuals, salicylates cross the placenta and are eliminated slowly in newborns, some persons are sensitive or allergic to aspirin, and children are at risk of Reye syndrome. Concurrent use with other salicylate-containing medicines increases these risks. Metabolism of 240 mg salicin from willow bark could yield 113 mg of salicylic acid, yet dietary supplement products are not required to be labeled with warnings. In contrast, over-the-counter low-dose aspirin (81 mg strength), which delivers 62 mg salicylic acid, is required by law to include cautions, warnings, and contraindications related to its use in pregnant and nursing women, children, and other vulnerable subpopulations, e.g., those using anticoagulants. In the interest of protecting public health, the United States Pharmacopeia has included a cautionary labeling statement in the United States Pharmacopeia Salix Species monograph as follows: "Dosage forms prepared with this article should bear the following statement: 'Not for use in children, women who are pregnant or nursing, or by persons with known sensitivity to aspirin.'".
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A complete review of empagliflozin: Most specific and potent SGLT2 inhibitor used for the treatment of type 2 diabetes mellitus.
Chawla, G, Chaudhary, KK
Diabetes & metabolic syndrome. 2019;(3):2001-2008
Abstract
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are the latest class of drugs to be introduced for the treatment of type 2 diabetes mellitus (T2DM). They reduce hyperglycemia by increasing urinary glucose excretion and exert favorable effects beyond glucose control with consistent body weight, blood pressure, and serum uric acid reductions. Empagliflozin is a potent SGLT2 inhibitor used to improve glycemic control in adults with T2DM. It has the highest SGLT2 specificity among all the clinically used or currently tested SGLT2 inhibitors. Low risk of hypoglycemia, absence of weight gain and demonstrated cardiovascular risk reduction support its consideration as a first line medication in addition to metformin for patients with T2DM and cardiovascular disease. Mostly reported adverse events are genital mycotic infections, while urinary tract infections and events linked to volume depletion are rather rare. This review covers the complete information on empagliflozin including the history of its development, synthesis, pharmacology and different methods which have been reported for its analysis.