Empagliflozin reduces body weight and indices of adipose distribution in patients with type 2 diabetes mellitus

Neeland, Ian J.; McGuire, Darren K.; Chilton, Robert; Crowe, Susanne; Lund, Søren S; Woerle, Hans J.; Broedl, Uli C.; Johansen, Odd Erik

doi:10.1177/1479164115616901

Cited by 132 publications

(111 citation statements)

References 25 publications

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“…However, the underlying mechanism for the benefit of empagliflozin in cardiovascular risk reduction remains to be determined. Interestingly, SGLT2 inhibitors including empagliflozin exert non-glycemic effect in type 2 diabetic patients [11, 21, 24–26] or animal models [16, 17, 19, 39], such as reduction in blood pressure, decrease in body weight, or natriuresis. Therefore, SGLT2 inhibition is proposed to provide cardiovascular protection partially independently of blood glucose control.…”

Section: Discussionmentioning

confidence: 99%

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Empagliflozin lessened cardiac injury and reduced visceral adipocyte hypertrophy in prediabetic rats with metabolic syndrome

Kurihara

Koibuchi

Hasegawa

et al. 2016

Cardiovasc Diabetol

123

104

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BackgroundThe potential benefit of SGLT2 inhibitors in metabolic syndrome is with prediabetic stage unclear. This work was undertaken to investigate the non-glycemic effect of empagliflozin on metabolic syndrome rats with prediabetes.MethodsSHR/NDmcr-cp(+/+) rats (SHRcp), a model of metabolic syndrome with prediabetes, were given empagliflozin for 10 weeks to examine the effects on urinary sodium and water balance, visceral and subcutaneous adipocyte, and cardiac injury. Further, the effect of empagliflozin on blood pressure and autonomic nervous system was continuously investigated by using radiotelemetry system.ResultsEmpagliflozin significantly reduced urinary sodium and water balance of SHRcp only within 1 week of the treatment, but later than 1 week did not alter them throughout the treatment. Empagliflozin significantly reduced body weight of SHRcp, which was mainly attributed to the significant reduction of subcutaneous fat mass. Empagliflozin significantly reduced the size of visceral adipocytes and increased the number of smaller size of adipocytes, which was associated with the attenuation of oxidative stress. Empagliflozin ameliorated cardiac hypertrophy and fibrosis of SHRcp, in association with the attenuation of cardiac oxidative stress and inflammation. However, empagliflozin did not significantly change blood pressure, heart rate, sympathetic activity, or baroreceptor function, as evidenced by radiotelemetry analysis.ConclusionsOur present work provided the evidence that SGLT2 inhibition reduced visceral adipocytes hypertrophy and ameliorated cardiac injury in prediabetic metabolic syndrome rat, independently of diuretic effect or blood pressure lowering effect. Thus, SGLT2 inhibition seems to be a promising therapeutic strategy for prediabetic metabolic syndrome.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-016-0473-7) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

“…Accumulating studies provide the solid evidence that long-term SGLT2 inhibition causes the reduction of body weight in type 2 diabetic patients [11, 24]. However, the underlying mechanism remains to be clarified.…”

Section: Discussionmentioning

confidence: 99%

Empagliflozin lessened cardiac injury and reduced visceral adipocyte hypertrophy in prediabetic rats with metabolic syndrome

Kurihara

Koibuchi

Hasegawa

et al. 2016

Cardiovasc Diabetol

123

104

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“…In pooled analyses, both doses decreased body weight by approximately 1.8 kg [24] and significant reductions were seen in waist circumference and the index of central obesity,[26] as well as visceral and abdominal subcutaneous adipose tissue. [9]…”

Section: Review Of Empagliflozinmentioning

confidence: 99%

A Safety Evaluation of Empagliflozin for the Treatment of Type 2 Diabetes

Neeland

Salahuddin

McGuire³

2016

Expert Opinion on Drug Safety

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Introduction Empagliflozin is a sodium glucose co-transporter 2 inhibitor used to improve glycemic control in adults with type 2 diabetes mellitus (T2DM) by enhancing urinary glucose excretion. Empagliflozin is effective at lowering glycosylated hemoglobin and was recently proven superior to placebo for reduction of cardiovascular disease (CVD) risk. As with any new drug, there are safety considerations that inform its potential use in patients with T2DM. Areas Covered Here, we evaluate the safety of empagliflozin and provide an expert opinion as to its current and future role in the treatment of patients with T2DM. A search of the English language literature was performed using PubMed search terms: “empagliflozin”, “sodium glucose cotransporter 2 inhibitors”, and “drug safety”. Articles and bibliographies relevant to the subject were reviewed and additional references known to the authors were included. Expert Opinion The evidence for empagliflozin is robust with regard to glycemic efficacy and safety. 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 CVD. Ongoing trials will continue to address the safety and efficacy of empagliflozin and expand our clinical knowledge of this medication.

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“…Several mechanisms have been postulated (Figure) including effects on osmotic diuresis and natriuresis contributing to blood pressure lowering without a compensatory increase in sympathetic nervous system activation (22), decreased arterial stiffness and vascular resistance (23), improvements in weight and visceral adiposity (24), decreases in uric acid and oxidative stress (25, 26), off-target effects on lipid metabolism, and a shift in myocardial fuel energetics (27). A recent theory suggests that SGLT2 inhibition may improve myocardial work efficiency based on a shift in fuel energetics with myocardial substrate metabolism switching away from free fatty acids and towards ketones, which are a more energy efficient fuel.…”

Section: Mechanisms For Cardiovascular Benefit In Heart Failurementioning

confidence: 99%

“…This result is a clinical weight loss of approximately 1.8 kg, as well as reductions in waist circumference and indices of total and visceral adiposity. (24) Visceral adiposity has been associated with adverse remodeling of the left ventricle and deranged hemodynamics such as lower cardiac output and increased systemic vascular resistance. (37) The benefit of empagliflozin on HF outcomes therefore could also be contributed to by these changes in body composition, although it is not likely not the primary mechanism.…”

Section: Mechanisms For Cardiovascular Benefit In Heart Failurementioning

confidence: 99%

Impact of empagliflozin in patients with diabetes and heart failure

Pham

Rocha

McGuire

et al. 2017

Trends in Cardiovascular Medicine

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Heart failure (HF) is a common disease with increased risk for mortality and morbidity among patients with type 2 diabetes mellitus (T2DM). Optimal glycemic control in this patient population is challenging as many available therapies can potentially exacerbate symptoms of HF. Empagliflozin is one in a novel class of agents, the sodium glucose co-transporter 2 (SGLT2) inhibitors, that lowers blood glucose by increasing urinary glucose excretion and improves glycemic control and lowers body weight and blood pressure. In the recent EMPA-REG OUTCOME trial, empagliflozin was shown to improve cardiovascular outcomes in patients with T2DM and established cardiovascular risk where it reduced HF hospitalizations and cardiovascular death, with a consistent benefit among patients both with and without baseline HF. Here, we review the empagliflozin data on HF outcomes and discuss potential mechanisms for its benefits in HF with a focus on the potentially significant impact that empagliflozin may have on the care of patients with T2DM and HF in the future.

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Empagliflozin reduces body weight and indices of adipose distribution in patients with type 2 diabetes mellitus

Cited by 132 publications

References 25 publications

Empagliflozin lessened cardiac injury and reduced visceral adipocyte hypertrophy in prediabetic rats with metabolic syndrome

Empagliflozin lessened cardiac injury and reduced visceral adipocyte hypertrophy in prediabetic rats with metabolic syndrome

A Safety Evaluation of Empagliflozin for the Treatment of Type 2 Diabetes

Impact of empagliflozin in patients with diabetes and heart failure

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