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Farxiga (dapagliflozin)
Farxiga (dapagliflozin)
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News & Research:
-
Is Dapagliflozin a Cardiac
Anti-Aging Drug? - Medscape, 5/1/23 - "At the
cardiac level, apart from improving renal or metabolic parameters, several
mechanisms have been put forward to explain the benefits of SGLT2 inhibitors. A
potential cardiac effect of SGLT2 inhibitors is the targeting of adverse cardiac
remodeling, which is a characteristic of HFrEF. It has been suggested that SGLT2
inhibitors may reverse cardiac remodeling by blocking the sodium-hydrogen
exchanger and/or by shifting cardiac metabolism toward consumption of
energy-efficient ketone bodies.[5] Some studies have reported reductions in
cardiac afterload with empagliflozin or dapagliflozin, with no reports proving a
reduction in left ventricular mass. Additional evidence indicates that SGLT2
inhibitors stimulate erythrocytosis, as a physiological response to hypoxia and
energy depletion. Together these results suggest that we may still miss some
pieces of the puzzle" - See
dapagliflozin at reliablerxpharmacy.com.
-
DELIVER Subanalysis 'Seals
Deal' for Dapagliflozin in HF - Medscape, 12/19/22 -
"The DELIVER analysis found that the effects of
dapagliflozin on reducing cardiovascular death and worsening HF were greatest in
patients who had the most debilitating symptoms at baseline, measured as KCCQ
total symptom score (TSS) as 63 or less, the lowest of three tertiles used in
the analysis. At baseline, these patients had the highest rates of CV death or
worsening HF than those in the other two tertiles: KCCQ-TSS of 63-84, and
greater than 84 ... Compared with placebo, treated patients in the lowest
KCCQ-TSS quartile had a 30% reduction in risk for the primary composite outcome,
which consisted of time to first CV death or HF event (hazard ratio, 0.70; 95%
confidence interval, 0.58-0.84; P < .001). In the second tertile, the relative
risk reduction was 19% (HR, 0.81; 95% CI, 0.65-1.01; P < .006), and the highest
quartile showed no significant difference between treatment and placebo (HR,
1.07; 95% CI, 0.83-1.37; P < .62)."
-
Dapagliflozin's HFpEF
Benefit Recasts Heart Failure Treatment: DELIVER - Medscape, 8/27/22 -
"A key finding of DELIVER, confirmed in several combined
analyses also reported at the congress, was that the benefit of dapagliflozin
treatment extended to patients with HFpEF in the highest ranges of ejection
fraction ... Combined analysis of the DELIVER results with the findings from
DAPA-HF in a prespecified analysis that included a total of 11,007 patients with
heart failure across the full spectrum of ejection fraction values (with
individual patients having values as low as less than 20% or as high as more
than 70%) showed a consistent benefit from dapagliflozin treatment for
significantly reducing the combined endpoint of cardiovascular death or
hospitalization for heart failure by about 22%, compared with placebo, across
the complete range of this ejection fraction continuum ... A second,
prespecified combined analysis coupled the DELIVER findings with the results of
a prior large trial that assessed empagliflozin in patients with HFpEF,
EMPEROR-Preserved, which had shown similar findings but with an apparent
diminishment of activity in patients at the highest range of preserved left
ventricular function, with ejection fractions in excess of about 65%, a tail-off
of effect not seen in DELIVER ... SGLT2 inhibitors are the bedrock of therapy
for heart failure regardless of ejection fraction or care setting"
-
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.
-
Effects of Dapagliflozin
in Patients With Kidney Disease, With and Without Heart Failure - Medscape,
1/3/22 - "Dapagliflozin reduced the risk of the primary
outcome equally in patients with HF (HR: 0.58 [95% CI: 0.37–0.91]) and without
HF (HR: 0.62 [95% CI: 0.51–0.75]) (P interaction = 0.59). The proportional
risk-reductions were similar in patients with and without HF for the
cardiovascular death/HF hospitalization composite (HR: 0.68 [95% CI: 0.44–1.05]
vs HR: 0.70 [95% CI: 0.51–0.97], respectively; P interaction = 0.90), and
all-cause death (HR: 0.56 [95% CI: 0.34–0.93] vs HR: 0.73 [95% CI: 0.54–0.97],
respectively; P interaction = 0.39), although absolute risk reductions were
larger in HF patients. Adverse event rates were low and did not differ among
patients with or without HF" - See
dapagliflozin at reliablerxpharmacy.com.
-
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"
-
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.
-
EU Approves Dapagliflozin
for Kidney Disease, Regardless of Diabetes - Medscape, 8/10/21 -
"We found that dapagliflozin delayed the initiation of
dialysis and reduced the number of deaths ... treatment with dapagliflozin led
to a 39% relative risk reduction in the incidence of a combined renal and
cardiovascular endpoint during a median 2.4 years of follow-up, with an absolute
risk reduction of 5.3%. The combined endpoint tallied the incidence of a 50% or
greater drop in eGFR from baseline, onset of end-stage renal disease, or renal
or cardiovascular death" - See
dapagliflozin at reliablerxpharmacy.com.
-
Dapagliflozin Misses as
Treatment for COVID-19 but Leaves Intriguing Signal for Benefit - Medscape,
5/18/21 - "At the end of 30 days, 11.2% of the
dapagliflozin group and 13.8% of the placebo group had an event. By hazard
ratio, dapagliflozin was linked to 20% nonsignificant relative protection from
events (hazard ratio, 0.80; 95% confidence interval, 0.58-1.10) ... The trend (P
= .168) for the primary endpoint for prevention was reflected in the individual
components. For dapagliflozin related to placebo, there were generally similar
or greater reductions in new or worsening organ failure (HR, 0.80), cardiac
decompensation (HR, 0.81), respiratory decompensation (HR, 0.85), and kidney
decompensation (HR, 0.65). None were statistically significant, but the
confidence intervals were tight with the upper end never exceeding 1.20 ...
Moreover, the relative risk reduction for all-cause mortality moved in the same
direction (HR, 0.77 ... In safety analyses, dapagliflozin consistently
outperformed placebo across a broad array of safety measure, including any
severe adverse event (65% vs. 82%), any adverse event with an outcome of death
(32% vs. 48%), discontinuation caused by an adverse event (44% vs. 55%), and
acute kidney injury (21% vs. 34%) ... These data show that these drugs are not
going to lead to harm, but they might lead to benefit"
-
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.
-
FDA Approves Dapagliflozin (Farxiga ) for Chronic Kidney Disease - Medscape,
4/30/21 - "Dapagliflozin was approved in 2014 to improve
glycemic control in patients with diabetes mellitus, and approval was expanded
in 2020 to include treatment of patients with heart failure and reduced ejection
fraction ... during a median of 2.4 years, treatment with dapagliflozin led to a
significant 31% relative reduction compared with placebo in the study's primary
outcome, a composite that included at least a 50% drop in estimated glomerular
filtration rate (eGFR) compared with baseline, end-stage kidney disease, kidney
transplant, renal death, or cardiovascular death ... Dapagliflozin treatment
also cut all-cause mortality by a statistically significant relative reduction
of 31%, and another secondary-endpoint analysis showed a statistically
significant 29% relative reduction in the rate of cardiovascular death or heart
failure hospitalization."
-
Dapagliflozin, Advanced
Chronic Kidney Disease, and Mortality: New Insights From the DAPA-CKD Trial
- Medscape, 4/28/21 - "Taken together, the data from DAPA-CKD, in conjunction
with the results from other recently published SGLT2 inhibitor trials in
patients with heart failure and reduced ejection fraction, position the class of
SGLT2 inhibitors far beyond their original use in patients with type 2 diabetes
(Graphical Abstract).[5,6,8] For the cardiovascular high-risk population of
patients with CKD, SGLT2 inhibition with dapagliflozin provides for the first
time a treatment option to significantly improve the prognosis and to reduce
mortality—independent of the presence of diabetes. Within the next few years,
additional studies with SGLT2 inhibitors in CKD patients will report (e.g.
EMPA-KIDNEY with empagliflozin, NCT03594110), but now it is on us—nephrologists,
cardiologists, and all healthcare providers treating patients with CKD—to ensure
that these life-saving therapies are implemented. For the treatment of patients
with diabetes, a subset of members of the writing groups of the 2019 American
Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD)
consensus document and the 2019 European Society of Cardiology (ESC) guidelines
have recently published a call for action to ensure that clinical inertia no
longer leads to the low prescription of evidence-based life-saving therapies in
high risk patients"
-
New DAPA-CKD Analysis
Hints at Dapagliflozin for IgA Nephropathy - Medscape, 4/20/21 -
"Dapagliflozin may be a novel therapeutic option to slow
kidney function decline in patients with IgA nephropathy"
-
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"
-
Dapagliflozin Reduces
Systolic Blood Pressure and Modulates Vasoactive Factors - Diabetes Obes
Metab 2021 Mar 17 - "24 and 23 patients receiving
dapagliflozin and placebo, respectively, completed the 12 weeks' study. Systolic
BP fell significantly, compared to placebo, both after a single dose (by 7 ± 3
mmHg) and 12-week (by 7 ± 2 mmHg) treatment with dapagliflozin. Dapagliflozin
suppressed angiotensin II and angiotensinogen (by 10.5 ± 2.1 pg/mL and 1.45 ±
0.42 μg/mL, respectively) and increased ANP and cGMP (by 34 ± 11 pg/mL and 29 ±
11 pmol/mL, respectively) compared to placebo group. cGMP levels also increased
acutely following a single dose of dapagliflozin. Dapagliflozin also suppressed
PDE5 expression by 26 ± 11% in MNC. There was no change in the other vasoactive
mediators investigated."
-
More From DAPA-HF:
Dapagliflozin Quickly Reduces Heart Failure Events - Medscape, 2/23/21 -
"These findings were consistent with the timing of
benefits for patients with heart failure with reduced ejection fraction (HFrEF)
in recent studies of two other drugs from the same class, the sodium-glucose
cotransporter (SGLT) inhibitors, including empagliflozin (Jardiance, which
inhibits SGLT-2) in the EMPEROR-Reduced trial, and sotagliflozin (Zynquista,
which inhibits both SGLT1 and -2) in the SOLOIST-WHF trial ... DAPA-HF
randomized 4,744 patients with HFrEF and in New York Heart Association
functional class II-IV at 410 sites in 20 countries. The incidence of the
primary, combined endpoint fell by 26% with dapagliflozin treatment,
compared with placebo, during a median 18-month follow-up. Among the study
cohort 27% of patients had been hospitalized for heart failure within a year
of their entry, 20% had been hospitalized for heart failure more than 1 year
before entry, and 53% had no history of a hospitalization for heart
failure."
Abstracts:
-
Dapagliflozin's HFpEF
Benefit Tied to Lower Filling Pressure - Medscape, 3/23/23 -
"Treatment of patients with heart failure with preserved
ejection fraction (HFpEF) with the SGLT2 inhibitor dapagliflozin (Farxiga) for
24 weeks produced significant and beneficial reductions in left-heart filling
pressures in a mechanistic, randomized clinical study ... Results from prior
studies documented the benefit of dapagliflozin for improving clinical outcomes
in patients with HFpEF in the DELIVER trial, and for the related sodium-glucose
cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) in the
EMPEROR-Preserved trial. The new findings presented by Dr. Borlaug provide
evidence from a placebo-controlled, prospective study for one way by which these
SGLT2 inhibitors exert this benefit in patients with HFpEF" - See
dapagliflozin at reliablerxpharmacy.com.
-
Dapagliflozin improves
pancreatic islet function by attenuating microvascular endothelial dysfunction
in type 2 diabetes - Diabetes Metab Res Rev 2022 Dec 24 -
"Sodium-glucose co-transporter type 2 (SGLT2)
inhibitors, including dapagliflozin, improve β cell function in type 2 diabetic
individuals. Whether dapagliflozin can protect islet microvascular endothelial
cells (IMECs) and thus contribute to the improvement of β cell function remains
unknown ... Dapagliflozin restores islet vascularization and attenuates the
inflammation of IMECs in type 2 diabetic mice. The dapagliflozin-induced
improvement of β cell function is at least partially accounted for by its
beneficial effects on IMECs in a PI3K/Akt-mTOR-dependent manner"
-
Dapagliflozin Reduces
Hospitalizations in Patients With CKD - Medscape, 12/7/22 -
"Compared with placebo, dapagliflozin significantly
reduced risk of first hospitalization by 16% (hazard ratio, 0.84; 95% confidence
interval, 0.75-0.94) and rate of all hospitalizations by 21% (rate ratio, 0.79;
95% CI, 0.70-0.89). These findings remained significant regardless of type 2
diabetes status, with significant benefits seen across reasons for admission,
including renal/urinary disorders, cardiac disorders, neoplasms, and
metabolism/nutrition disorders. In addition, dapagliflozin was associated with
shorter mean time in hospital (2.3 vs. 2.8 days; P = .027) and longer time alive
and out of hospital (354.9 vs. 351.7; P = .023)."
-
Liver autophagy-induced
valine and leucine in plasma reflect the metabolic effect of sodium glucose
co-transporter 2 inhibitor dapagliflozin - EBioMedicine 2022 Nov 21 -
"Sodium glucose co-transporter 2 (SGLT2) inhibitors are
anti-diabetic drugs for type 2 diabetes that lower blood glucose levels and body
weight. It is of special interest that SGLT2 inhibitors also improve liver
metabolism and fatty liver. Liver is an important organ in regulation of energy
metabolism, but the metabolic action of SGLT inhibitors in liver remains unclear
... Clinical study found that valine and leucine levels were markedly higher in
patients treated with dapagliflozin (valine: P < 0·05 vs. control, leucine: P <
0·01 vs. control) than those not treated after one week intervention ...
Dapagliflozin improves liver metabolism via hepatic autophagy, and plasma valine
and leucine levels may reflect its metabolic effect"
-
Effect of dapagliflozin on
cardiac function and metabolic and hormonal responses to exercise - J Clin
Endocrinol Metab 2022 Oct 24 - "During the exercise
protocol glucose and lactate were lower (p < 0.0001, p < 0.05 respectively) and
β-hydroxybutyrate (BOBH) and growth hormone (GH) were higher (p < 0.0005, p =
0.01) following dapagliflozin treatment compared to placebo. There was a trend
for lower insulin with dapagliflozin. Adrenalin, noradrenalin and glucagon were
not different. Following dapagliflozin participants demonstrated an increased
mean peak diastolic mitral annular velocity (e') in comparison to placebo (p =
0.03). The indexed left atrial volume and right ventricular e' were reduced
following dapagliflozin compared with placebo (p = 0.045, p = 0.042
respectively). Arterial stiffness was not different between treatments
(dapagliflozin 9.35 ± 0.60m/s; placebo 9.07 ± 0.72 m/s)"
-
DELIVER May Demystify Med
Therapy in Heart Failure With Improved LVEF - Medscape, 10/6/22 -
"As recently reported, DELIVER entered HF patients with
an LVEF greater than 40%, that is, HF with either mildly reduced or preserved
ejection fraction (HFmrEF or HFpEF, respectively). Those assigned to
dapagliflozin (Farxiga) vs placebo over 2 years overall showed an 18% drop (P =
.0008) in risk for the primary endpoint, worsening HF or cardiovascular (CV)
death ... The new analysis centered on the 18% of patients in the trial with an
initial LVEF greater than 40%, per entry criteria, but who previously were
symptomatic with an LVEF of 40% or lower, that is, HF with reduced ejection
fraction (HFrEF) ... Their ostensible dapagliflozin benefit was comparable as
well; they showed a significant 26% decrease in risk for worsening HF or CV
death compared to the control group ... The HFimpEF patients in DELIVER
benefited significantly from dapagliflozin for both the composite primary
endpoint and the CV-death component, for which the risk reduction reached a
significant 38%"
-
Estimated Event-Free
Survival Benefits with Dapagliflozin in HF with Mildly Reduced or Preserved
Ejection Fraction - J Am Coll Cardiol 2022 Aug 24 -
"Treatment with dapagliflozin is projected to extend event-free survival by up
to 2-2.5 years among middle age and older individuals with HF with mildly
reduced, preserved, or improved ejection fraction" - See
dapagliflozin at reliablerxpharmacy.com.
-
Dapagliflozin in Patients
Recently Hospitalized With Heart Failure and Mildly Reduced or Preserved
Ejection Fraction - J Am Coll Cardiol 2022 Aug 26 -
"Dapagliflozin safely reduced risk of worsening HF or cardiovascular death
similarly in patients with and without history of recent HF hospitalization.
Starting dapagliflozin during or shortly after HF hospitalization in patients
with mildly reduced or preserved LVEF appears safe and effective. (Dapagliflozin
Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction
Heart Failure"
-
Dapagliflozin for heart
failure according to body mass index: the DELIVER trial - Eur Heart J 2022
Aug 27 - "Obesity is common in patients with HFpEF and
is associated with higher rates of heart failure hospitalization and worse
health status. Treatment with dapagliflozin improves cardiovascular outcomes
across the spectrum of BMI, leads to greater symptom improvement in patients
with obesity, compared to those without, and has the additional benefit of
causing modest weight loss"
-
Dapagliflozin and Prevention
of Kidney Disease Among Patients With Type 2 Diabetes-Post Hoc Analyses From the
DECLARE-TIMI 58 Trial - Diabetes Care 2022 Aug 23 -
"Dapagliflozin mitigated kidney function decline in patients with T2D at high
cardiovascular risk, including those with low KDIGO risk, suggesting a role of
dapagliflozin in the early prevention of diabetic kidney disease"
-
Iron Deficiency in Heart
Failure and Effect of Dapagliflozin: Findings From DAPA-HF - Circulation
2022 Aug 16 - "Iron deficiency is common in heart
failure and associated with worse outcomes. We examined the prevalence and
consequences of iron deficiency in the DAPA-HF trial (Dapagliflozin and
Prevention of Adverse-Outcomes in Heart Failure) and the effect of dapagliflozin
on markers of iron metabolism ... Transferrin saturation, ferritin, and hepcidin
were reduced and total iron-binding capacity and soluble transferrin receptor
increased with dapagliflozin compared with placebo ... Iron deficiency was
common in DAPA-HF and associated with worse outcomes. Dapagliflozin appeared to
increase iron use but improved outcomes, irrespective of iron status at
baseline"
-
SGLT2 inhibitor
dapagliflozin attenuates cardiac fibrosis and inflammation by reverting the
HIF-2α signaling pathway in arrhythmogenic cardiomyopathy - FASEB J 2022 Jul
- "Excessive cardiac fibrosis and inflammation aberrantly contribute to the
progressive pathogenesis of arrhythmogenic cardiomyopathy (ACM) ...
dapagliflozin (DAPA ... DAPA not only significantly ameliorated cardiac
dysfunction, adverse remodeling, and ventricular dilation in ACM but also
attenuated ACM-associated cardiac fibrofatty replacement, as demonstrated by the
echocardiography and histopathological examination ... SGLT2i attenuated the
ACM-associated cardiac dysfunction and adverse remodeling in a
glucose-independent manner by suppressing cardiac fibrosis and inflammation via
reverting the HIF-2α signaling pathway, suggesting that SGLT2i is a novel and
available therapy for ACM" - See
dapagliflozin at reliablerxpharmacy.com.
-
Arrhythmogenic cardiomyopathy - Wikipedia -
"Arrhythmogenic cardiomyopathy
(ACM), arrhythmogenic right ventricular dysplasia (ARVD), or
arrhythmogenic right ventricular cardiomyopathy (ARVC), most
commonly is an inherited heart disease ... ACM is caused by
genetic defects of the parts of heart muscle (also called
myocardium or cardiac muscle) known as desmosomes, areas on
the surface of heart muscle cells which link the cells
together. The desmosomes are composed of several proteins,
and many of those proteins can have harmful mutations ...
ARVC can also develop in intense endurance athletes in the
absence of desmosomal abnormalities. Exercise-induced ARVC
cause possibly is a result of excessive right ventricular
wall stress during high intensity exercise"
-
Dapagliflozin Attenuates
Sympathetic and Pressor Responses to Stress in Young Prehypertensive
Spontaneously Hypertensive Rats - Hypertension 2022 Jun 2 -
"These data demonstrate a novel role for SGLT2i in
reducing resting BP as well as the activity of skeletal muscle reflexes,
independent of glycemic control. Our study may have important clinical
implications for preventing hypertension and hypertensive heart disease in young
prehypertensive individuals" - See
dapagliflozin at reliablerxpharmacy.com and
empagliflozin inhousepharmacy.vu. From what I've read,
empagliflozin sounds like a better product.
-
Dapagliflozin improves
endothelial cell dysfunction by regulating mitochondrial production via the
SIRT1/PGC-1α pathway in obese mice - Biochem Biophys Res Commun 2022 May 10
- "dapagliflozin (DAPA) ... DAPA improves endothelial
cell mitochondrial function in obese mice by activating the SIRT1/PGC-1α
pathway"
-
Dapagliflozin Improves Body Fat Patterning, and Hepatic and
Pancreatic Fat in Patients with Type 2 Diabetes in North India
- Int J Food Sci Nutr 2022 Mar 9 -
"Excess hepatic and pancreatic fat may contribute to
hyperglycemia ... Patients (n, 30) were given dapagliflozin
10mg/day (on top of stable dose of metformin and/or
sulphonylureas) for a period of 120 day ... After 120 days of
treatment with dapagliflozin, a significant reduction in weight,
body mass index (BMI), body fat, circumferences, and all
skinfold thickness was seen. A significant reduction in blood
glucose, hemoglobin A1c, hepatic transaminases, fasting insulin,
homeostatic model assessment -insulin resistance (HOMA-IR), and
postprandial C-peptide was noted while HOMA-beta, post parandial
insulin sensitivity and fasting adiponectin were significantly
increased. There was no change in lean body mass. Compared to
baseline there was a significant decrease in mean liver fat
fraction (from15.2 to 10.1%, p <0.0001) and mean pancreatic fat
fraction (from 7.5 to 5.99%, p <0.0083). Reduction in liver fat
was significant after adjustment for change in body weight"
-
Dapagliflozin for
nonalcoholic fatty liver disease: a systematic review and meta-analysis -
Diabetes Res Clin Pract 2022 Feb 21 - "Compared with the
control conditions, dapagliflozin led to a greater decrease in alanine
transaminase, aspartate transaminase, gamma-glutamyl transferase, triglyceride,
body weight, body mass index, HbA1c, and fasting plasma glucose ...
Dapagliflozin can markedly reduce hepatic enzymes and metabolic indicators and
improve body composition, indicating its potential therapeutic efficacy"
-
Metabolic Changes Induced by
Dapagliflozin, an SGLT2 Inhibitor, in Japanese Patients with Type 2 Diabetes
Treated by Oral Anti-diabetic Agents: A Randomized, Clinical Trial -
Diabetes Res Clin Pract 2022 Feb 15 - "We aimed to
determine whether SGLT2 inhibitor dapagliflozin treatment affects body
composition and amino acid (AA) metabolis ... Dapagliflozin treatment causes a
reduction in BM mainly by reducing fat mass. AA metabolism shows subtle changes
with dapagliflozin treatment"
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Quantifying the relationship
between dapagliflozin and loss of weight in type 1 diabetes mellitus patients
- J Clin Pharm Ther 2021 Nov 9 - "Dapagliflozin was the
first oral treatment approved in type 1 diabetes mellitus (T1DM) patients,
simultaneously improving body weight ... Five dapagliflozin dosage groups, two
of them were 5 mg/day and three of them were 10 mg/day, 1612 T1DM patients were
analysed with maximal effect (Emax ) model, and evaluation index was change rate
of body weight from baseline value ... In these T1DM patients, dosages were not
incorporated into model, indicating no significant dose-response relationship
between 5 and 10 mg/day affecting loss of weight. Emax and the treatment
duration to reach half of the maximal effects (ET50 ) of dapagliflozin
influencing loss of weight in T1DM patients were -4.9% and 10.4 weeks, and the
duration to achieve 25%, 50%, 75%, and 80% (plateau) of Emax were 3.5, 10.4,
31.2, and 41.6 week ... To achieve the plateau period in loss of weight, 5
mg/day dapagliflozin was required for at least 41.6 weeks"
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Exploring the Effect of
Dapagliflozin on Alcoholic Kidney Injury and Renal Interstitial Fibrosis in Rats
Based on TIMP-1/MMP-24 Pathway - Evid Based Complement Alternat Med 2021 Oct
21 - "Long-term large-scale alcohol intake can cause
kidney tissue damage and fibrotic lesions. The expression of fibrotic cytokines
such as TIMP-1 and Smad3 will increase, and the expression of MMP-24 will be
decreased. However, dapagliflozin and losartan have certain therapeutic effects
on the abovementioned lesions. The mechanism may be downregulating TIMP-1 and
Smad3 and upregulating the expression of MMP-24 and other cytokines in the
kidney"
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Exploring the Effect of
Dapagliflozin on Alcoholic Kidney Injury and Renal Interstitial Fibrosis in Rats
Based on TIMP-1/MMP-24 Pathway - Evid Based Complement Alternat Med 2021 Oct
21 - "Long-term large-scale alcohol intake can cause
kidney tissue damage and fibrotic lesions. The expression of fibrotic cytokines
such as TIMP-1 and Smad3 will increase, and the expression of MMP-24 will be
decreased. However, dapagliflozin and losartan have certain therapeutic effects
on the abovementioned lesions. The mechanism may be downregulating TIMP-1 and
Smad3 and upregulating the expression of MMP-24 and other cytokines in the
kidney"
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Effects of SGLT-2 inhibitors
on serum uric acid in patients with T2DM: A systematic review and network
meta-analysis - Diabetes Obes Metab 2021 Oct 6 -
"serum uric acid (SUA) ... SGLT-2 inhibitors could significantly reduce SUA
levels in patients with T2DM, especially luseogliflozin (1 mg and 10 mg) and
dapagliflozin (5 mg) possess the best effects. Therefore, SGLT-2 inhibitors look
extremely promising as an anti-diabetes treatment option in patients with T2DM
with high SUA"
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PRESERVED-HF:
Dapagliflozin Improves Physical Limitations in Patients With HFpEF -
Medscape, 9/14/21 - "These results in the PRESERVED-HF
study follow closely on the heals of the initial report from the
EMPEROR-Preserved trial that showed a benefit from a different sodium-glucose
cotransporter 2 (SGLT2) inhibitor, empagliflozin (Jardiance) in nearly 6,000
randomized patients for the primary endpoint of preventing cardiovascular death
or hospitalizations for heart failure ... In PRESERVED-HF, patients with HFpEF
who received a standard, once-daily dose of dapagliflozin (Farxiga) had an
average 5.8-point improvement in their condition as measured by the Kansas City
Cardiomyopathy Questionnaire clinical summary score (KCCQ-CS), the study's
primary endpoint ... The impact of empagliflozin on KCCQ clinical summary score
in EMPEROR-Preserved showed an average incremental improvement of 1.32 points
compared with placebo, a significant difference, but more modest than the
increment from dapagliflozin treatment seen in PRESERVED-HF. Kosiborod
hypothesized that this difference might be mostly because of the different
patient populations enrolled in the two studies" - See
dapagliflozin at reliablerxpharmacy.com.
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Dapagliflozin in HFrEF May
Cut Arrhythmias, Sudden Death: DAPA-HF - Medscape, 8/27/21 -
"The addition of dapagliflozin to standard therapy
reduced the relative risk for the primary composite endpoint of any serious
ventricular arrhythmia, resuscitated cardiac arrest, or sudden death by 21%,
compared with placebo"
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The Effect of Dapagliflozin
on Albuminuria in DECLARE-TIMI 58 - Diabetes Care 2021 Jul 7 -
"Urinary albumin-to-creatinine ratio (UACR) ...
dapagliflozin demonstrated a favorable effect on UACR and renal-specific outcome
across baseline UACR categories, including patients with normal albumin
excretion. The results suggest a role for SGLT2i also in the primary prevention
of diabetic kidney disease"
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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.
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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.
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Effects of the SGLT2
Inhibitor Dapagliflozin on Energy Metabolism in Patients With Type 2 Diabetes: A
Randomized, Double-Blind Crossover Trial - Diabetes Care 2021 Apr 15 -
"SGTL2 inhibitors increase urinary glucose excretion and
have beneficial effects on cardiovascular and renal outcomes. The underlying
mechanism may involve caloric restriction-like metabolic effects due to urinary
glucose loss ... Dapagliflozin treatment for 5 weeks resulted in major
adjustments of metabolism mimicking caloric restriction, increased fat
oxidation, improved hepatic and adipose insulin sensitivity, and improved 24-h
energy metabolism"
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Effects of dapagliflozin on
mortality in patients with chronic kidney disease: a pre-specified analysis from
the DAPA-CKD randomized controlled trial - Eur Heart J 2021 Mar 31 -
"Mortality rates from chronic kidney disease (CKD) have
increased in the last decade. In this pre-specified analysis of the DAPA-CKD
trial, we determined the effects of dapagliflozin on cardiovascular and
non-cardiovascular causes of death ... The relative risk reduction for all-cause
mortality with dapagliflozin (31%, hazard ratio [HR] [95% confidence interval
(CI)] 0.69 [0.53, 0.88]; P = 0.003) was consistent across pre-specified
subgroups. The effect on all-cause mortality was driven largely by a 46%
relative risk reduction of non-cardiovascular death (HR [95% CI] 0.54 [0.36,
0.82]). Deaths due to infections and malignancies were the most frequently
occurring causes of non-cardiovascular deaths and were reduced with
dapagliflozin vs. placebo ... In patients with CKD, dapagliflozin prolonged
survival irrespective of baseline patient characteristics. The benefits were
driven largely by reductions in non-cardiovascular death"
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