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Home > Health Conditions > Diabetes > Jardiance (empagliflozin)

Jardiance (empagliflozin)

Also see "SGLT2 Inhibitors".

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News & Research:

  • Moving the Needle: SGLT2 Inhibitor Role for Isolated Kidney Disease - Medscape, 11/4/22 - "In the new trial, EMPA-Kidney, treatment with empagliflozin 10 mg daily for a median of 2.0 years led to a significant 28% relative risk reduction in the primary combined endpoint in comparison with placebo" - See empagliflozin inhousepharmacy.vu.
  • Empagliflozin and Elderly Patients With Preserved Ejection Fraction Heart Failure: Is Age Just a Number? - Medscape, 10/17/22 - "Major molecular regulators of cellular lifespan are sirtuin-1 (SIRT1) and mammalian target of rapamycin complex 1 (mTORC1). In a nutrient-deficient or calorie-restricted state, SIRT1 activation, along with adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α) set forth a cascade of downstream target activations culminating in deceleration of cell aging. Suppression of the mTORC1 pathway further augments SIRT1-activated autophagy, the lysosome-utilizing process of clearing misfolded proteins from the cytosol. Without healthy autophagy, oxidative stress contributes to impaired endothelial nitric oxide (NO) pathways, inflammation, cell death, fibrosis, and cardiomyopathy (adapted from Gevaert et al1). SGLT2 inhibitors are hypothesized to contribute to activation of SIRT1 and suppression of mTORC1 pathways.10 Akt = protein kinase B; HFpEF = heart failure with preserved ejection fraction; ROS = reactive oxygen species ... Aside from the obvious bedside clinical implications, the findings of Bohm et al[7] cause us to wonder more about the mechanistic impact of SGLT2 inhibition on multiple cardiovascular and noncardiovascular therapeutic targets. SGLT2 inhibitors induce glycosuria and reduce insulin levels, which promotes a ketogenic and fatty acid oxidation state, mimicking calorie restriction physiology, which has been associated with cellular stress resistance, attenuation of cellular senescence, and reduced oxidative stress-induced tissue damage.[9] Such pathway activation is hypothesized to assuage metabolic disease, alleviate endothelial and vascular inflammation, and mitigate the clinically observed arterial stiffness associated with the HFpEF syndrome" - See empagliflozin inhousepharmacy.vu.
  • Empagliflozin and Elderly Patients With Preserved Ejection Fraction Heart Failure: Is Age Just a Number? - Medscape, 10/17/22 - "Major molecular regulators of cellular lifespan are sirtuin-1 (SIRT1) and mammalian target of rapamycin complex 1 (mTORC1). In a nutrient-deficient or calorie-restricted state, SIRT1 activation, along with adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α) set forth a cascade of downstream target activations culminating in deceleration of cell aging. Suppression of the mTORC1 pathway further augments SIRT1-activated autophagy, the lysosome-utilizing process of clearing misfolded proteins from the cytosol. Without healthy autophagy, oxidative stress contributes to impaired endothelial nitric oxide (NO) pathways, inflammation, cell death, fibrosis, and cardiomyopathy (adapted from Gevaert et al1). SGLT2 inhibitors are hypothesized to contribute to activation of SIRT1 and suppression of mTORC1 pathways.10 Akt = protein kinase B; HFpEF = heart failure with preserved ejection fraction; ROS = reactive oxygen species ... Aside from the obvious bedside clinical implications, the findings of Bohm et al[7] cause us to wonder more about the mechanistic impact of SGLT2 inhibition on multiple cardiovascular and noncardiovascular therapeutic targets. SGLT2 inhibitors induce glycosuria and reduce insulin levels, which promotes a ketogenic and fatty acid oxidation state, mimicking calorie restriction physiology, which has been associated with cellular stress resistance, attenuation of cellular senescence, and reduced oxidative stress-induced tissue damage.[9] Such pathway activation is hypothesized to assuage metabolic disease, alleviate endothelial and vascular inflammation, and mitigate the clinically observed arterial stiffness associated with the HFpEF syndrome" - See empagliflozin inhousepharmacy.vu.
  • Early Flozin Use Tied to Improved LA Strain in ACS With Diabetes - Medscape, 7/5/22 - "The addition of the SGLT2 inhibitor empagliflozin to routine acute coronary syndrome (ACS) medications significantly improved left atrial (LA) reservoir and contractile strain. These changes were not seen in most conventional diastolic function markers or in patients who did not receive the agent ... SGLT2 inhibitors might be unique among glucose-lowering agents in their ability to improve diastolic cardiac remodeling"
  • Empagliflozin Eyed for Outpatient Chronic Hyponatremia - Medscape, 6/21/22 - "Empagliflozin is a potential treatment for outpatients with chronic hyponatremia due to the syndrome of inappropriate antidiuresis (SIAD) ... Hyponatremia, defined as a serum sodium level below 135 mmol/L, is the most common electrolyte disorder in both the inpatient and outpatient settings. SIAD is one of its main causes, whereby impaired antidiuretic hormone regulation leads to a reduction in free water excretion and water retention in the kidney, with subsequent hypotonic hyponatremia ... Serum sodium levels remained stable with placebo while increasing from 130 mmol/L to 134 mmol/L with empagliflozin, giving a corresponding treatment effect of 4.1 mmol/L (P = .004). The increase took place during the first week of treatment and plasma sodium levels remained stable through subsequent weeks ... there's accumulating evidence that these patients have cognitive impairments such as attention deficit, that they are unstable when walking with a propensity to fall, and that they have increased risk for osteoporosis and fractures, and even death" - Note: Sounds like that could be a bad think if you blood sodium is high.
  • SGLT2 Inhibitors Cut AFib Risk in Real-Word Analysis - Medscape, 6/14/22 - "But despite documentation like this, real-world evidence also continues to show limited uptake of SGLT2 inhibitors in U.S. patients with type 2 diabetes. Records from more than 1.3 million patients with type 2 diabetes managed in the Veterans Affairs Healthcare System during 2019 or 2022 documented that just 10% of these patients received an agent from this class, even though all were eligible to receive it, according to findings in a separate report at the meeting ... The study's primary endpoint was the incidence of hospitalization for AFib, which occurred a significant 18% less often in the patients who started on an SGLT2, compared with those who started a DPP4 inhibitor during median follow-up of 6.7 months, and a significant 10% less often, compared with those starting a GLP-1 receptor agonist during a median follow-up of 6.0 months ... in an analysis of more than 130,000 matched pairs, treatment with empagliflozin was linked to a significant 30% reduction in the incidence of hospitalization for heart failure, compared with patients treated with a GLP-1 receptor agonist. Analysis of more than 116,000 matched pairs of patients showed that treatment with empagliflozin linked with a significant 29%-50% reduced rate of hospitalization for heart failure, compared with matched patients treated with a DPP4 inhibitor" - See empagliflozin inhousepharmacy.vu.
  • Dapagliflozin Early Benefit Explored in Reduced-EF Heart Failure - Medscape, 6/6/22 - "Functional capacity in heart failure with reduced ejection fraction (HFrEF) appears to improve within a few weeks of SGLT2-inhibitor initiation, suggests a small, randomized study that followed peak VO2 in patients with HFrEF assigned to take dapagliflozin (Farxiga). The benefit observed at 30 days held at a plateau for at least a few more months ... The new study, called DAPA-VO2 , has limitations but is consistent with a similar study of empagliflozin (Jardiance), investigators observed, and could help explain why clinical risk fell off so rapidly once patients started on SGLT2 inhibitors in major HFrEF trials of these drugs ... Peak VO2 in the study rose 8% further (P = .021) in patients on dapagliflozin compared with placebo a month into the trial, the gain persisting at least to 90 days" - See empagliflozin inhousepharmacy.vu.
  • Empagliflozin Rapidly Improves Acute Heart Failure Symptoms in Hospitalized Patients - Medscape, 4/14/22 - "The trial randomized patients hospitalized for acute heart failure after a brief period of stabilization regardless of their left ventricular ejection fraction or presence of diabetes to receive a single, daily dose of 10 mg of empagliflozin (Jardiance) or placebo starting a median of 3 days after admission ... Using a “win ratio” method for analyzing the composite endpoint, the primary analysis showed that treatment with empagliflozin for 90 days boosted the win ratio by a significant 36% relative to placebo (Nature Med. 2022 Mar;28[3]: 568-74) ... EMPULSE is the second trial to show that an SGLT2 inhibitor can safely and effectively treat patients hospitalized for acute heart failure. Previously, results from the SOLOIST-WHFpivotal trial, which enrolled 1,222 patients with type 2 diabetes recently hospitalized for worsening heart failure, showed that treatment with an investigational, combined SGLT2 and SGLT1 inhibitor, sotagliflozin, resulted in a significant, 33% relative reduction in the primary outcome compared with placebo after a median 9 months of treatment." - See empagliflozin inhousepharmacy.vu.
  • Heart Failure With Preserved Ejection Fraction: New Treatments Provide 'Hope' - Medscape, 3/28/22 - "That is, those individuals in PARAGON-HF who had ejection fractions slightly on the lower end of "normal" tended to benefit more from this medication as well. That differentiated by sex. This is a controversial aspect of the field and it is something that's evolving on a day-to-day or month-to-month basis ... Sacubitril-valsartan, I think, would be a medicine that could be of particular benefit in this patient. That was the first of the next few trials in HFpEF that started to yield potential new drug classes for HFpEF. ... The next drug class is one with which all aspects of cardiology have become more and more aware, and the HFpEF field is no stranger. With the results of the EMPEROR-Preserved trial we have, in the history of HFpEF clinical trials, our first positive trial, and a monumental moment. A trial evaluating the efficacy of empagliflozin (a sodium-glucose cotransporter 2 [SGLT2] inhibitor) vs placebo in HFpEF. This is the ideal patient who may benefit from this medicine ... EMPEROR-Preserved demonstrated a reduction in a composite endpoint of heart failure hospitalization and cardiovascular death. As you mentioned, Clyde, this efficacy was driven by a reduction in heart failure hospitalization. The class of SGLT2 inhibitors would be, certainly, a medicine that would provide much benefit not only from a reduction in heart failure hospitalization perspective, but a marked improvement in symptoms"
  • Empagliflozin and decreased risk of nephrolithiasis: A potential new role for SGLT2 inhibition? - J Clin Endocrinol Metab 2022 Mar 15 - "Diabetes mellitus is a risk factor for nephrolithiasis. A recent observational study found that SGLT2 inhibitor use by type 2 diabetes (T2D) patients was associated with a 49% lower risk of nephrolithiasis, compared to GLP-1 receptor agonist ... Compared to placebo, empagliflozin therapy was associated with an approximate 40% reduced risk of urinary tract stone events in T2D patients"
  • Empagliflozin Scores Topline Win in EMPA-KIDNEY Trial - Medscape, 3/17/22 - "EMPA-KIDNEY is the third major trial of an agent from the sodium-glucose co-transport 2 (SGLT2) inhibitor class tested in patients with CKD to be stopped early because of positive results that met a prespecified termination rule ... The success of empagliflozin in EMPA-KIDNEY follows its positive results in both the EMPEROR-Reduced and EMPEROR-Preserved trials, which collectively proved the efficacy of the agent for patients with heart failure regardless of their left ventricular ejection fraction and regardless of whether they also had diabetes"
  • FDA Okays Empagliflozin for HF Regardless of Ejection Fraction - Medscape, 2/24/22 - "That means the SGLT2 inhibitor, once considered primarily an antidiabetic agent, is approved for use in patients with HF per se without regard to ventricular function ... The study saw a significant 21% relative reduction in that composite endpoint over about 2 years in patients with NYHA class II-IV heart failure and an LVEF greater than 40% who received empagliflozin along with other standard care"
  • SGLT2 Inhibitors in Older Adults with Heart Failure with Preserved Ejection Fraction - Drugs Aging 2022 Feb 4 - "Until now, empagliflozin is the first therapy that has convincingly been shown to improve clinical outcome in HFpEF. Importantly, some key points should be considered to better understand the impact of empagliflozin on the patient trajectory, particularly in older adults with HFpEF. In this current opinion article, we have therefore provided more information on how to translate the findings of the EMPEROR-Preserved trial to the setting of older adults, with a focus on the impact of empagliflozin on hospitalizations, both heart failure-related and all-cause. To better understand the importance of EMPEROR-Preserved findings, we compared these findings with previous relevant HFpEF and heart failure with reduced ejection fraction (HFrEF) trials and provided information on ongoing trials in the HFpEF setting"
  • The diabetes medication that could revolutionize heart failure treatment - Science Daily, 12/1/21 - "For many years there was not a single medicine that could improve the outcome in patients with the second type of heart failure -- those patients with preserved ejection fraction ... SGLT2 inhibitors are more commonly known under their trade-names Forxiga (Dapagliflozin), Invokana (Canagliflozin), and Jardiance (Empagliflozin) ... We found that patients taking SGLT2 inhibitors were 22 per cent less likely to die from heart-related causes or be hospitalised for heart failure exacerbation than those taking placebo" - See dapagliflozin at reliablerxpharmacy.com.
  • EMPEROR-Preserved Findings Confirmed in 'True' HFpEF Patients - Medscape, 11/18/21 - "The demonstration that empagliflozin is an effective — and safe — treatment for patients with HFpEF not only provides a new treatment for a disorder that until now had no evidence-based intervention, but also streamlines the management approach for treating patients with heart failure with an agent from empagliflozin's class, the SGLT2 inhibitors ... The impact of empagliflozin, compared with placebo, for reducing both the study's combined, primary outcome as well as total HHF was statistically consistent across all strata of LVEF, from 50% to greater than 70% ... Patients' quality of life as measured by the Kansas City Cardiomyopathy Questionnaire showed a consistent benefit from empagliflozin treatment, compared with placebo, both in patients with an LVEF of at least 50% as well as in those with an LVEF of 41%-49% ... Deterioration of renal function on treatment slowed by an average 1.24 mL/min per 1.73 m2 per year in patients on empagliflozin, compared with placebo, in the subgroup with an LVEF of at least 50%"
  • Empagliflozin a Winner in Challenging Arena of Stabilized Acute HF - Medscape, 11/16/21 - "Patients assigned to empagliflozin had a 36% greater likelihood of showing a benefit as reflected in the treatment's win ratio when opposed by placebo ... The trial also lends new weight to the strategy of "simultaneous or rapid-sequence initiation" of the so-called four pillars of guideline-directed medical therapy of HF with reduced ejection fraction (HFrEF) in patients hospitalized with HFrEF, once they are stabilized, Fonarow said. The four-pronged approach, he noted, consists of sacubitril/valsartan (Entresto), a beta blocker, a mineralocorticoid receptor antagonist (MRA), and an SGLT2 inhibitor ... EMPULSE entered patients hospitalized for acute HF, which could be de novo or a decompensation of chronic HF, without regard to ejection fraction or whether they had diabetes, and who were clinically stable after at least one dose of loop diuretics. Their ejection fractions averaged 35% and exceeded 40% in about one third of the total cohort ... At 90 days in the win ratio analysis, the 265 patients assigned to empagliflozin 10 mg once daily were the "winners," that is, they were more likely to show a clinical benefit about 54% of the time in paired match-ups of patient outcomes, compared to about 40% for the 265 in the control group ... The empagliflozin group also benefited significantly for the endpoint of death from any cause or first HF event, with a hazard ratio (HR) of 0.65 (95% CI, 0.43 - 0.99, P = .042). They also were less likely to experience acute renal failure (7.7% vs 12.1% for the control group) or serious adverse events (32.3% vs 43.6%), Voors reported ... several ongoing trials are exploring dapagliflozin (Farxiga) in a similar clinical setting" - See dapagliflozin at reliablerxpharmacy.com.  They don't have empagliflozin.
  • Adults with acute heart failure benefit when treated with a type 2 diabetes medication - AHA, 11/14/21 - "When treated with empagliflozin, adults hospitalized for acute heart failure were 36% more likely to have a clinical benefit, such as a reduction in all-cause mortality, reduction in heart failure events, or an improvement in heart failure symptoms"
  • Advanced CKD Doesn't Derail Empagliflozin in EMPEROR-Preserved - Medscape, 11/12/21 - "The results showed, in a prespecified analysis, that treatment with empagliflozin led to a consistent, significant relative risk reduction compared with placebo in the primary endpoint of cardiovascular death or hospitalization for heart failure "across the full spectrum of kidney function, down to an eGFR of 20 mL/min/1.73m2," said Faiez Zannad, MD, PhD, who presented the findings at virtual Kidney Week 2021 ... Among the 46.5% of enrolled patients without CKD, empagliflozin produced a significant 20% drop in the primary outcome relative to those who received placebo. Among the 53.5% of patients with CKD at time of randomization (defined as an eGFR < 60 mL/min/1/73m2 or a urinary albumin to creatinine ratio > 300 mg/g), treatment with empagliflozin was associated with a significant 25% cut in the primary endpoint compared with placebo"
  • Empagliflozin's HFpEF Efficacy Catalyzes Redefinition of HF - Medscape, 9/22/21 - "This new consensus essentially throws out left ventricular ejection fraction (EF) as the key metric for matching patients to heart failure treatments. Experts have instead begun suggesting a more unified treatment approach for all heart failure patients regardless of their EF ... We encourage you to forget about ejection fraction ... We certainly encourage you to forget about an ejection fraction of less than 40%" as having special significance ... The 40% ejection fraction divide is artificial. It was created in 2003 as part of a trial design, but it has no physiological significance ... A much better way to distinguish systolic and diastolic heart failure is by strain assessment rather than by ejection fraction. "Strain is a measure of myocardial shortening, a measure of what the heart does. Ejection fraction is a measure of volume," ... Wouldn't it be easier if we said that every patient with heart failure needs to receive one agent from each of the four [pillar] drug classes, and put them in a polypill ... The four pillar drug classes, recently identified as essential for patients with HFrEF but until now not endorsed for patients with HFpEF, are the sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as empagliflozin (Jardiance); an angiotensin receptor blocker neprilysin inhibitor compound such as sacubitril/valsartan (Entresto); beta-blockers; and mineralocorticoid receptor antagonists such as spironolactone and eplerenone ... The consequence is that clinicians should feel comfortable prescribing empagliflozin to most patients with heart failure without regard to EF, even patients with EF values in the mid-60% range ... The EMPEROR-Preserved results showed a clear signal of attenuated benefit among patients with an EF of 65% or greater "on a population basis," ... Recently, data from a third trial that tested sacubitril/valsartan in patients with HFpEF, PARAGON-HF, showed benefit among patients with EFs below the study median of 57%"
  • FDA Okays Empagliflozin for HFrEF - Medscape, 8/19/21 - "The FDA based its decision on results from the EMPEROR-Reduced study, first reported in August 2020, that showed treatment of patients with HFrEF with empagliflozin on top of standard therapy for a median of 16 months cut the incidence of cardiovascular death or hospitalization for worsening heart failure by 25% relative to placebo, and by an absolute 5.3%, compared with placebo-treated patients ... Patients enrolled in EMPEROR-Reduced had chronic heart failure in New York Heart Association functional class II-IV and with a left ventricular ejection fraction of 40% or less, the standard ejection fraction criterion for defining HFrEF. Half the enrolled patients had diabetes, and analysis showed no heterogeneity in the primary outcome response based on diabetes status at enrollment ... Subsequent to the report of results from the EMPEROR-Reduced trial nearly a year ago, heart failure experts declared that treatment with an agent from the SGLT2 inhibitor class had become a "new pillar of foundational therapy for HFrEF," and they urged rapid initiation of an SGLT2 inhibitor (along with other appropriate medications) at the time of initial diagnosis of HFrEF"
  • Tips for Navigating Prior Authorization and Out-of-Pocket Costs for HFrEF Medications - Medscape, 5/11/21 - "Moreover, in the past decade, a series of large randomized trials have shown the efficacy of newer classes of medications in improving health outcomes of patients with HFrEF. These newer medications include the I f inhibitor ivabradine (SHiFT study); the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril-valsartan (PARADIGM-HF and PIONEER-HF trials); the sodium-glucose transporter 2 (SGLT2) inhibitors dapagliflozin (DAPA-HF study) and empagliflozin (EMPEROR-Reduced trial); and the soluble guanylate cyclase activator vericiguat (VICTORIA trial) ... Although these new treatment options for HFrEF are proven to be safe and well tolerated across a wide range of patients, there are obstacles to their widespread use — namely, the high cost of these drugs, prior authorization requirements, and out-of-pocket fees. Not only must patients often first obtain approval from their insurance companies for these prescriptions, but they are also required to pay greater out-of-pocket costs for them than generic drugs. Perhaps not surprisingly, the use of generic ACE inhibitors and beta-blockers for HFrEF remains high, whereas uptake of ivabradine and sacubitril-valsartan continues to be slow and SGLT2 inhibitors are only just beginning to be prescribed." - See dapagliflozin at ReliableRXPharmacy.  They don't carry empagliflozin, which in my view is better.  I read somewhere that India would no longer sell generic versions after a certain patent date until that drug goes generic.  I think that's the problem with buying generic empagliflozin from India.
  • Diabetes Drug Can Treat and Reverse Heart Failure and Reduce Hospitalizations - mountsinai.org - "Roughly 80 percent of the patients treated with empagliflozin showed significant improvement, and their hearts returned to near normal, the researchers found. This group had a 16.6 percent improvement in left ventricular ejection fraction at the six-month mark and their hearts pumped blood in a stronger way. Their hearts became smaller, less dilated because of less congestion and less fluid accumulation in the body, meaning that their heart failure became less severe, and the walls of the heart were less thick, meaning that the left ventricle could pump blood more easily"
  • Which Antidiabetic Drug Class is Most Renoprotective? - Medscape, 12/2/20 - "All three of the newer drug classes performed better than the sulfonylureas. Both SGLT2i and GLP-1a offered greater renoprotection than DPP-4i, but neither was notably better than the other, according to the analysis. These findings held for patients at various levels of early and advanced chronic kidney disease and were independent of whether the patients were taking metformin" - Note: Jardiance is a SGLT2 inhibitor.
  • SCORED and FIDELIO-DKD: Time for Cardiologists to Help, Not Hurt, the Kidney - Medscape, 11/20/20 - 20 minute video on empagliflozin (Jardiance).  I doubt if most cardiologists are even aware of this yet. - "In terms of heart failure with reduced EF, these are really well-tolerated medicines. I've been using dapagliflozin and empagliflozin in my patients and found them to have good clinical outcomes and to be clinically well tolerated, with minimal side effects"
  • Diabetes drug can treat and reverse heart failure and reduce hospitalizations - Science Daily, 11/16/20 - "Empagliflozin, a recently developed diabetes drug ... this medication can improve the heart's size, shape, and function, leading to better exercise capacity and quality of life, which will reduce hospitalizations for heart failure patients" - Note:  It's a $500/month medication.
  • EMPEROR-Reduced: Empagliflozin's HFrEF Benefit Holds Steady on Top of Sacubitril/Valsartan - Medscape, 10/7/20 - "When there are two very effective treatments, it's common for people to ask: Which should I use?' The goal of my presentation was to emphasize that the answer is both. We shouldn't choose between neprilysin inhibition [sacubitril inhibits the enzyme neprilysin] and SGLT2 [sodium-glucose transporter 2] inhibition; we should use both"

Abstracts:

  • Low-Dose Empagliflozin as Adjunct to Hybrid Closed-Loop Insulin Therapy in Adults With Suboptimally Controlled Type 1 Diabetes: A Randomized Crossover Controlled Trial - Diabetes Care 2022 Nov 4 - "Empagliflozin at 2.5 and 5 mg increased time in range during hybrid closed-loop therapy by 11-13 percentage points compared with placebo in those who otherwise were unable to attain glycemic targets. Future studies are required to assess long-term efficacy and safety" - See empagliflozin inhousepharmacy.vu.
  • The SGLT2 inhibitor empagliflozin reduces tissue sodium content in patients with chronic heart failure: results from a placebo-controlled randomised trial - Clin Res Cardiol 2022 Oct 26 - "This trial showed a significant decrease in skin sodium content after 1 and 3 months of treatment with empagliflozin. The decrease in skin sodium content may reflect a decrease in subclinical micro-oedema or/and in non-osmotic bound tissue sodium, both reported to impair left ventricular function"
  • Serum Uric Acid Lowering With Empagliflozin in Heart Failure With Reduced Ejection Fraction - Medscape, 10/26/22 - "SUA was reduced by an average of 1.12 mg/dL (66.2 μmol/L) with empagliflozin vs. placebo in this study, a relatively modest reduction compared with that achievable with xanthine oxidase inhibitors such as allopurinol.[12] However, the modest reduction in urate in EMPEROR-Reduced was associated with a significant 32% reduction in adverse gout outcomes. This is important because hyperuricaemia, and also clinical gout, often co-exist with heart failure, and this causes difficulties with therapeutic choices in the management of patients, particularly with diuretics that can worsen hyperuricaemia. Empagliflozin treatment in EMPEROR-Reduced was also associated with an impressive 30% reduction in hospitalizations for heart failure, which was the main driver of the 25% reduction in the primary outcome of first hospitalization for heart failure or cardiovascular death. However, interestingly, this finding was independent of the decrease in SUA observed with empagliflozin therapy"
  • Early Signal of Benefit for Empagliflozin in Acute MI: EMMY - Medscape, 9/2/22 - "SGLT2 inhibitors have shown benefits in patients with heart failure (HF) across the spectrum of left ventricular function, reducing the risk for HF hospitalization and cardiovascular death in low ejection fraction (EF) in last year's EMPEROR-Preserved and the newly reported DELIVER trial. SGLT2 inhibitors also lower the risk for incident HF in such high-risk groups as those with type 2 diabetes or chronic kidney disease ... Left ventricular EF improved in both groups, with those assigned to empagliflozin having a 1.5% absolute higher EF at week 26 (P = .029). The E/e′ ratio was significantly improved, being 6.8% lower than placebo ... The structural markers of left ventricular end systolic volume (–7.5 mL; P = .0003) and LV end diastolic volume (–9.7 mL; P = .0015) improved as well, and were smaller in the empagliflozin group"
  • Empagliflozin has favourable effect on frontal plane QRS-T angle in diabetic patients with cardiovascular disease - J Clin Pharm Ther 2022 Jul 15 - "Empagliflozin leads a significant narrowing in the fQRST angle in type 2 DM patients with known CVD"
  • A metabonomics-based renoprotective mechanism analysis of empagliflozin in obese mice - Biochem Biophys Res Commun 2022 Jul 6 - "Our study revealed the metabonomics-based renoprotective mechanism of empagliflozin in obese mice for the first time. Empagliflozin may be a promising tool to delay the progression of obesity-related kidney disease" - See empagliflozin inhousepharmacy.vu.
  • Uric acid and sodium-glucose cotransporter-2 inhibition with empagliflozin in heart failure with reduced ejection fraction: the EMPEROR-reduced trial - Eur Heart J 2022 Jul 5 - "Hyperuricaemia is common in HF and is an independent predictor of advanced disease severity and increased mortality. Empagliflozin induced a rapid and sustained reduction of SUA levels and of clinical events related to hyperuricaemia. The benefit of empagliflozin on the primary outcome was observed independently of SUA"
  • Empagliflozin Improves Outcomes in Patients With Heart Failure and Preserved Ejection Fraction Irrespective of Age - J Am Coll Cardiol 2022 Jul 5 - "Empagliflozin reduces cardiovascular death (CVD) or heart failure (HF) hospitalization (HFH) in patients with HF and preserved ejection fraction. ... Empagliflozin reduced primary outcomes and first and recurrent HFH and improved symptoms across a broad age spectrum. High age was not associated with reduced efficacy or meaningful intolerability"
  • Empagliflozin for Heart Failure With Preserved Left Ventricular Ejection Fraction With and Without Diabetes - Circulation 2022 Jun 28 - "In patients with heart failure and a preserved ejection fraction enrolled in EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction), empagliflozin significantly reduced the risk of heart failure outcomes irrespective of diabetes status at baseline"
  • Could a Type 2 Diabetes Drug Tackle Kidney Stones? - Medscape, 6/20/22 - "Patients with type 2 diabetes who received empagliflozin, a sodium glucose cotransporter-2 (SGLT2) inhibitor, were almost 40% less likely to have a kidney stone than patients who received placebo during a median 1.5 years of treatment ... Because SGLT2 inhibitors increase urinary glucose excretion through reduced renal reabsorption of glucose leading to osmotic diuresis and increased urinary flow, they hypothesized that these therapies "may reduce the risk of upper urinary tract stones (nephrolithiasis) by reducing the concentration of lithogenic substances in urine.
  • SGLT2 Inhibition via Empagliflozin Improves Endothelial Function and Reduces Mitochondrial Oxidative Stress: Insights From Frail Hypertensive and Diabetic Patients - Hypertension 2022 Jun 15 - "Frailty is a multidimensional condition often diagnosed in older adults with hypertension and diabetes, and both these conditions are associated with endothelial dysfunction and oxidative stress ... Taken together, our data indicate that empagliflozin reduces frailty in diabetic and hypertensive patients, most likely by decreasing mitochondrial reactive oxygen species production in endothelial cells"
  • The effects of empagliflozin, dietary energy restriction, or both on appetite-regulatory gut peptides in individuals with type 2 diabetes and overweight or obesity: the SEESAW randomised, double-blind, placebo-controlled trial - Diabetes Obes Metab 2022 Apr 19 - "68 adults (age 30-75 years) with T2D (drug naïve or on metformin monotherapy; HbA1c 6.0-10.0% [42-86mmol/mol]) and BMI ≥25kg/m2 were randomised to: (1) placebo-only, (2) placebo-plus-diet, (3) empagliflozin-only, or (4) empagliflozin-plus-diet for 24 weeks ... The mean weight loss in each group at 24 weeks was 0.44, 1.91, 2.22, and 5.74 kg, respectively"
  • Cardiovascular benefits of empagliflozin are associated with gut microbiota and plasma metabolites in type 2 diabetes - J Clin Endocrinol Metab 2022 Apr 9 - "empagliflozin may be a superior initial therapy for patients with T2DM at risk of CVDs; its cardiovascular benefits may be associated with shifts in gut microbiota and plasma metabolites"
  • Empagliflozin in patients with type 2 diabetes mellitus and chronic obstructive pulmonary disease - Diabetes Res Clin Pract 2022 Mar 18 - "In patients with T2DM and CVD, COPD increased the risk of mortality and cardiorenal outcomes, including HF. Empagliflozin consistently reduced these outcomes versus placebo regardless of COPD, suggesting that empagliflozin's benefits in patients with T2DM and CVD are not mitigated by the presence of COPD"
  • Empagliflozin Improves Cognitive Impairment in Frail Older Adults With Type 2 Diabetes and Heart Failure With Preserved Ejection Fraction - Diabetes Care 2022 Mar 14 - "This study is the first to show significant beneficial effects of the SGLT2 inhibitor empagliflozin on cognitive and physical impairment in frail older adults with diabetes and HFpEF"
  • Effect of empagliflozin in patients with heart failure across the spectrum of left ventricular ejection fraction - Eur Heart J 2021 Dec 8 - "The magnitude of the effect of empagliflozin on heart failure outcomes was clinically meaningful and similar in patients with ejection fractions <25% to <65%, but was attenuated in patients with an ejection fraction ≥ 65%"
  • The effect of empagliflozin on the total burden of cardiovascular and hospitalization events in the Asian and non-Asian populations of the EMPA-REG OUTCOME trial of patients with type 2 diabetes and cardiovascular disease - Diabetes Obes Metab 2021 Dec 14 - "Among 1517 Asian participants, empagliflozin reduced relative risk of total events of the primary outcome by 38% versus placebo (rate ratio [95% CI]: 0.62 [0.427, 0.885]), the key secondary outcome by 33% (0.67 [0.479, 0.929]), the composite of cardiovascular death (excluding fatal stroke) and hospitalization for heart failure by 43% (0.57 [0.329, 0.996]), and all-cause hospitalization by 21% (0.79 [0.651, 0.967]). Empagliflozin's effects were consistent between Asian and non-Asian populations"
  • Beneficial Effect of Sodium-Glucose Co-transporter 2 Inhibitors on Left Ventricular Function - J Clin Endocrinol Metab 2021 Nov 15 - "Treatment with SGLT2 inhibitors can significantly improve LV function in patients with or without diabetes (especially those with HF or undergoing empagliflozin treatment)"
  • Clinical benefits of empagliflozin in very old patients with type 2 diabetes hospitalized for acute heart failure - J Am Geriatr Soc 2021 Nov 29 - "There is little evidence on the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors in older patients with heart failure. This work analyzed the clinical efficacy and safety of empagliflozin continuation in very old patients with type 2 diabetes hospitalized for acute decompensated heart failure ... In very old patients with type 2 diabetes hospitalized for acute heart failure, continuing preadmission empagliflozin reduced NT-proBNP levels and increased diuretic response and urine output compared to a basal-bolus insulin regimen. The empagliflozin regimen also showed a good safety profile" - See dapagliflozin at reliablerxpharmacy.com.  They don't carry empagliflozin.
  • Empagliflozin, Health Status, and Quality of Life in Patients with Heart Failure and Preserved Ejection Fraction: The EMPEROR-Preserved Trial - Circulation 2021 Nov 15 - "Patients with heart failure and preserved ejection fraction (HFpEF) have significant impairment in health-related quality of life (HRQoL) ... The effect of empagliflozin on reducing the risk of time to cardiovascular death or HF hospitalization was consistent across baseline KCCQ-CSS tertiles (HR 0.83 [0.69-1.00], HR 0.70 [0.55-0.88] and HR 0.82 [0.62-1.08] for scores <62.5, 62.5-83.3 and ≥83.3, respectively; P trend=0.77). Similar results were seen for total HF hospitalizations. Patients treated with empagliflozin had significant improvement in KCCQ-CSS versus placebo (+1.03, +1.24 and +1.50 at 12, 32 and 52 weeks, respectively P<0.01); similar results were seen for TSS and OSS. At 12 weeks, patients on empagliflozin had higher odds of improvement ≥5 points (OR 1.23; 95%CI 1.10, 1.37), ≥10 points (1.15; 95%CI 1.03, 1.27), and ≥15 points (1.13; 95%CI 1.02, 1.26) and lower odds of deterioration ≥5 points in KCCQ-CSS (0.85; 95%CI 0.75, 0.97). A similar pattern was seen at 32 and 52 weeks, and results were consistent for TSS and OSS"
  • Cost-Effectiveness of Empagliflozin in Patients With Diabetic Kidney Disease in the United States: Findings Based on the EMPA-REG Outcome Trial - Am J Kidney Dis 2021 Nov 6 - "Based on EMPA-REG Outcome Study, this cost-effectiveness analysis suggests that for commercial insurers and Medicare, adding empagliflozin to SoC may be a cost-effective treatment option for patients with DKD"
  • Empagliflozin Improves Insulin Sensitivity of the Hypothalamus in Humans With Prediabetes: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial - Diabetes Care 2021 Oct 29 - "Insulin action in the human brain reduces food intake, improves whole-body insulin sensitivity, and modulates body fat mass and its distribution. Obesity and type 2 diabetes are often associated with brain insulin resistance, resulting in impaired brain-derived modulation of peripheral metabolism. So far, no pharmacological treatment for brain insulin resistance has been established. Since sodium-glucose cotransporter 2 (SGLT2) inhibitors lower glucose levels and modulate energy metabolism, we hypothesized that SGLT2 inhibition may be a pharmacological approach to reverse brain insulin resistance ... We identified a significant interaction between time and treatment in the hypothalamic response to insulin. Post hoc analyses revealed that only empagliflozin-treated patients experienced increased hypothalamic insulin responsiveness. Hypothalamic insulin action significantly mediated the empagliflozin-induced decrease in fasting glucose and liver fat ... Our results corroborate insulin resistance of the hypothalamus in humans with prediabetes. Treatment with empagliflozin for 8 weeks was able to restore hypothalamic insulin sensitivity, a favorable response that could contribute to the beneficial effects of SGLT2 inhibitors. Our findings position SGLT2 inhibition as the first pharmacological approach to reverse brain insulin resistance, with potential benefits for adiposity and whole-body metabolism"
  • Randomized Trial of Empagliflozin in Nondiabetic Patients With Heart Failure and Reduced Ejection Fraction - J Am Coll Cardiol 2021 Jan 26 - "Empagliflozin was associated with a significant reduction of LV end-diastolic volume (-25.1 ± 26.0 ml vs. -1.5 ± 25.4 ml for empagliflozin vs. placebo, respectively; p < 0.001) and LV end-systolic volume (-26.6 ± 20.5 ml vs. -0.5 ± 21.9 ml for empagliflozin vs. placebo; p < 0.001). Empagliflozin was associated with reductions in LV mass (-17.8 ± 31.9 g vs. 4.1 ± 13.4 g, for empagliflozin vs. placebo, respectively; p < 0.001) and LV sphericity, and improvements in LV ejection fraction (6.0 ± 4.2 vs. -0.1 ± 3.9; p < 0.001). Patients who received empagliflozin had significant improvements in peak O2 consumption (1.1 ± 2.6 ml/min/kg vs. -0.5 ± 1.9 ml/min/kg for empagliflozin vs. placebo, respectively; p = 0.017), oxygen uptake efficiency slope (111 ± 267 vs. -145 ± 318; p < 0.001), as well as in 6-min walk test (81 ± 64 m vs. -35 ± 68 m; p < 0.001) and quality of life (Kansas City Cardiomyopathy Questionnaire-12: 21" - See empagliflozin inhousepharmacy.vu.
  • Prognostic Importance of NT-proBNP and Effect of Empagliflozin in the EMPEROR-Reduced Trial - J Am Coll Cardiol 2021 Sep 28 - "In EMPEROR-Reduced, higher baseline NT-proBNP concentrations were associated with greater risk for adverse heart failure or renal outcomes, but empagliflozin reduced risk regardless of baseline NT-proBNP concentration"
  • Empagliflozin and uric acid metabolism in diabetes: A post hoc analysis of the EMPA-REG OUTCOME tri - Diabetes Obes Metab 2021 Sep 24 - "Empagliflozin reduced UA levels and the composite of gout episodes or prescription of antigout medication. These clinically important findings expand the utility of empagliflozin as a potential antigout treatment in patients with T2D, beyond its well-established cardio-renal benefits"
  • EMPEROR-Preserved: Empagliflozin Scores HFpEF Breakthrough - Medscape, 8/27/21 - "The SGLT2 inhibitor empagliflozin achieved in EMPEROR-Preserved what no other agent could previously do: unequivocally cut the incidence of cardiovascular death or hospitalization in patients with heart failure and preserved ejection fraction (HFpEF) ... Treatment with empagliflozin (Jardiance) led to a significant 21% relative reduction in the rate of cardiovascular death or hospitalization for heart failure (HHF), compared with placebo, among 5,988 randomized patients with HFpEF during a median 26 months of follow-up, proving that patients with HFpEF finally have a treatment that gives them clinically meaningful benefit, and paving the way to an abrupt change in management of these patients, experts said ... A second sodium-glucose cotransporter 2 (SGLT2 ) inhibitor, dapagliflozin (Farxiga), is also an option for treating HFrEF based on results in the DAPA-HF trial, and the DELIVER trial, still in progress, is testing dapagliflozin as a HFpEF treatment in about 6,000 patients, with results expected in 2022 ... This showed a consistent and robust benefit from empagliflozin for reducing HHF across a wide spectrum of patients with heart failure, ranging from patients with left ventricular ejection fractions of less than 25% to patients with ejection fractions as high as 64% ... patients with reduced ejection fractions showed a significant 49% relative reduction in the incidence of serious renal outcomes" - Note:  If you can't get empagliflozin, ReliableRxPharmacy sells dapagliflozin.
  • Effects of Empagliflozin on Erythropoiesis in Patients with Type 2 Diabetes - data from a randomized, placebo controlled study - Diabetes Obes Metab 2021 Aug 11 - "Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been shown to significantly reduce heart failure hospitalization (HHF) and cardiovascular (CV) mortality in various cardiovascular outcome trials in patients with and without type 2 diabetes mellitus (T2D). SGLT2 inhibition further increased haemoglobin concentration and hematocrit by a yet unknown mechanism and this increase proved as an independent predictor for the CV benefit of these agent ... 44 patients with T2D were randomized into 2 groups and received empagliflozin 10 mg or placebo for a period of 3 months ... Empagliflozin increased hemoglobin concentrations and hematocrit with a delayed time kinetic which was most likely attributable to increased erythropoiesis with augmented iron utilization and not hemoconcentration. This might be attributable to reduced tubular glucose reabsorption in response to SGLT2 inhibition possibly resulting in diminished cellular stress as a mechanism for increased renal erythropoietin secretion"
  • Effects of empagliflozin on lipoprotein subfractions in patients with type 2 diabetes: data from a randomized, placebo-controlled study - Atherosclerosis 2021 Jun 25 - "Empagliflozin treatment of patients with T2D increased LDL-C and LDL apolipoprotein B levels but had no effect on calculated LDL particle size"
  • Usefulness of Sodium-Glucose Cotransporter 2 Inhibitors for Primary Prevention of Heart Failure in Patients With Type 2 Diabetes Mellitus - Am J Cardiol 2021 May 15 - "The sodium-glucose cotransporter 2 inhibitors (SGLT2i) empagliflozin, canagliflozin, and dapagliflozin reduce the risk of heart failure (HF) events in patients with diabetes mellitus (DM) at high risk for HF. Differences in HF outcomes between SGLT2i were demonstrated in a recent-published meta-analysis ... Our findings suggest that between the available SGLT2i, the cost of primary prevention of HF in patients with DM at high risk for HF is lowest with empagliflozin" - See dapagliflozin at ReliableRXPharmacy.  They don't carry empagliflozin, which in my view is better.  I read somewhere that India would no longer sell generic versions after a certain patent date until that drug goes generic.  I think that's the problem with buying generic empagliflozin from India.
  • Effect of empagliflozin on cardiorenal outcomes and mortality according to body-mass index: A subgroup analysis of the EMPA-REG OUTCOME trial with a focus on Asia - Diabetes Obes Metab 2021 May 5 - "Overall, hazard ratios for empagliflozin versus placebo for all-cause mortality, HHF or CV death, and incident or worsening nephropathy were 0.68 (95% CI 0.57, 0.82), 0.66 (0.55, 0.79), and 0.61 (0.53, 0.70), respectively, and were consistent across BMI categories (P-values for interaction between treatment and BMI: 0.6772, 0.3087, and 0.6265, respectively). Results were similar in Asians using these BMI categories and < 24, 24 to <28, ≥28 kg/m2 categories. Thus, empagliflozin reduced cardiorenal and mortality risk regardless of BMI at baseline, including in Asians with lower BMI"
  • Are SGLT2 Inhibitors New Hypertension Drugs? - Circulation 2021 May 4 - Note:  See the table. Jardiance (empagliflozin) lowered systolic by about 10 points.  Farxiga (dapagliflozin) was 5.8.
  • Cardiac and Kidney Benefits of Empagliflozin in Heart Failure Across the Spectrum of Kidney Function - Medscape, 3/29/21 - "Empagliflozin reduced the primary outcome and total HF hospitalizations in patients with and without CKD: hazard ratio (HR)=0.78 (95% CI, 0.65–0.93) and HR=0.72 (95% CI, 0.58–0.90), respectively (interaction P=0.63). Empagliflozin slowed the slope of eGFR decline by 1.11 (0.23–1.98) ml/min/1.73 m2/yr in patients with CKD and by 2.41 (1.49–3.32) ml/min/1.73 m2/yr in patients without CKD. The risk of the composite kidney outcome was reduced similarly in patients with and without CKD: HR=0.53 (95% CI, 0.31–0.91) and HR=0.46 (95% CI, 0.22–0.99), respectively. The effect of empagliflozin on the primary composite outcome and key secondary outcomes was consistent across a broad range of baseline kidney function, measured by clinically relevant eGFR subgroups or by albuminuria, including patients with eGFR as low as 20 ml/min/1.73 m2. Empagliflozin was well tolerated in CKD patients ... In EMPEROR-Reduced, empagliflozin had a beneficial effect on the key efficacy outcomes and slowed the rate of kidney function decline in patients with and without CKD, and regardless of the severity of kidney impairment at baseline."
  • SGLT-2 inhibitors for prevention of cardiorenal outcomes in type 2 diabetes: an updated meta-analysis - Diabetes Obes Metab 2021 Mar 12 - "A total of 8 cardiorenal outcomes trials of SGLT-2i (empagliflozin, canagliflozin, dapagliflozin, ertugliflozin, sotagliflozin) were identified, with 66 601 patients ... Overall, SGLT-2i were associated with a 12% reduced risk of major adverse cardiovascular events (MACE, HR = 0.88; 95% CI, 0.83-0.93; Q statistic, P = 0.19), with no significant heterogeneity (p for interaction = 0.465) between subgroups of patients with or without cardiovascular disease (CVD). The risk of the composite renal outcome was significantly reduced by treatment with SGLT-2i (HR = 0.61, 95% CI, 0.54-0.70), with no significant heterogeneity of associations with outcome (I2 = 37%, P = 0.11), and no difference in the risk between patients with or without CVD (p for interaction = 0.665). SGLT-2i have moderate benefits on MACE and major benefits on the progression of diabetic kidney disease"
  • The role of SGLT-2 inhibitors in managing type 2 diabetes - Cleve Clin J Med 2020 Dec 31 - "Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are an exceptionally versatile class of medication, and their glycemic and nonglycemic benefits could help millions of patients with type 2 diabetes. Of note, they have been shown to improve cardiac and renal outcomes, much-needed benefits in patients with type 2 diabetes, who are at a higher risk for developing cardiac and renal dysfunction than those who do not have diabetes. The indications for SGLT-2 inhibitors may continue to expand as ongoing clinical trials provide more insight into these drugs"
  • Effects of SGLT2 inhibitors on eGFR in type 2 diabetic patients-the role of antidiabetic and antihypertensive medications - Hypertens Res 2020 Dec 14 - "metformin blunts the SGLT2i-induced decrease in eGFR, but coadministration of RASis ameliorates this response. Furthermore, the inability of CCBs to modify the SGLT2i-induced reduction in eGFR suggests that the SGLT2i-induced renal microvascular action is mediated predominantly by postglomerular vasodilation rather than preglomerular vasoconstriction" - Note:  Normal eGFR is >60.  I threw this in because the diabetes medication and SGLT2 inhibitor Jardiance (empagliflozin) is also being used to help repair the heart in heart failure patients.
  • Randomized Trial of Empagliflozin in Non-Diabetic Patients with Heart Failure and Reduced Ejection Fraction - J Am Coll Cardiol 2020 Nov 9 - "Empagliflozin administration to non-diabetic HFrEF patients significantly improves LV volumes, LV mass, LV systolic function, functional capacity, and quality of life when compared with placebo. Our observations strongly support a role for SGLT2 inhibitors in the treatment of HFrEF patients independently of their glycemic status"