scholarly journals Impact of SGLT2 Inhibitors on Heart Failure: From Pathophysiology to Clinical Effects

2021 ◽  
Vol 22 (11) ◽  
pp. 5863
Author(s):  
Giuseppe Palmiero ◽  
Arturo Cesaro ◽  
Erica Vetrano ◽  
Pia Clara Pafundi ◽  
Raffaele Galiero ◽  
...  
Keyword(s):  
Heart Failure ◽  
Glucose Transporter ◽  
The Elderly ◽  
Intracellular Sodium ◽  
Clinical Effects ◽  
Glucose Lowering ◽  
Beneficial Effects ◽  
Glucose Transporter 2 ◽  
Function Impairment

Heart failure (HF) affects up to over 20% of patients with type 2 diabetes (T2DM), even more in the elderly. Although, in T2DM, both hyperglycemia and the proinflammatory status induced by insulin resistance are crucial in cardiac function impairment, SGLT2i cardioprotective mechanisms against HF are several. In particular, these beneficial effects seem attributable to the significant reduction of intracellular sodium levels, well-known to exert a cardioprotective role in the prevention of oxidative stress and consequent cardiomyocyte death. From a molecular perspective, patients’ exposure to gliflozins’ treatment mimics nutrient and oxygen deprivation, with consequent autophagy stimulation. This allows to maintain the cellular homeostasis through different degradative pathways. Thus, since their introduction in the clinical practice, the hypotheses on SGLT2i mechanisms of action have changed: from simple glycosuric drugs, with consequent glucose lowering, erythropoiesis enhancing and ketogenesis stimulating, to intracellular sodium-lowering molecules. This provides their consequent cardioprotective effect, which justifies its significant reduction in CV events, especially in populations at higher risk. Finally, the updated clinical evidence of SGLT2i benefits on HF was summarized. Thus, this review aimed to analyze the cardioprotective mechanisms of sodium glucose transporter 2 inhibitors (SGLT2i) in patients with HF, as well as their clinical impact on cardiovascular events.

scholarly journals Contemporary National Patterns of Eligibility and Utilization of Novel Cardioprotective Anti‐hyperglycemic agents in Type 2 Diabetes

2021 ◽  
Author(s):  
Arash A Nargesi ◽  
Gini P Jeyashanmugaraja ◽  
Nihar Desai ◽  
Kasia Lipska ◽  
Harlan Krumholz ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Clinical Trials ◽  
High Risk ◽  
Glucose Transporter ◽  
Survey Design ◽  
Atherosclerotic Cardiovascular Disease ◽  
Glucose Transporter 2 ◽  
Number Of Patients

Abstract Background Sodium glucose transporter‐2 (SGLT‐2) inhibitors and glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) effectively lowered cardiovascular risk in large clinical trials for patients with type 2 diabetes at high risk for these complications, and have recommended by guidelines. To evaluate the contemporary landscape in which these recommendations would be implemented, we examined the use of these medications according to clinical guideline practice. Methods and Results In the National Health and Nutrition Examination Survey for 2017‐2018, we defined compelling indications for SGLT‐2 inhibitors by the presence of atherosclerotic cardiovascular disease (ASCVD), heart failure, or chronic kidney disease (CKD), and for GLP‐1RAs by the presence of established or high risk ASCVD, based on large clinical trials that have been incorporated in guideline recommendations of the American College of Cardiology (ACC) and American Diabetes Association (ADA). We then evaluated utilization of these medications among patients with physician‐diagnosed type 2 diabetes. All analyses incorporated complex survey design to produce nationally representative estimates. A total 1104 of 9254 sampled individuals had type 2 diabetes, representing 10.6% (95% CI 9.7‐11.6) of the US population or 33.2 million adults nationally. Of these, 52.6% (47.7‐57.5) had an indication for SGLT‐2 inhibitors, 32.8% (28.8‐37.2) for GLP‐1RAs, and 26.6% (22.2‐31.7) for both medications. During 2017‐2018, 4.5% (2.4‐8.2) were treated with SGLT‐2 inhibitors and 1.5% (0.7‐3.2) with GLP‐1RAs. ASCVD, heart failure, or CKD were not independently associated with SGLT‐2 inhibitor or GLP‐1RA use in patients with diabetes. Conclusions Despite a large number of patients being eligible for guideline recommended cardiorenal protective therapies, there are substantial gaps in the use of SGLT‐2 inhibitors and GLP‐1RAs, limiting their public health benefits.

Dapagliflozin for heart failure – is it a class effect?

2020 ◽  
Author(s):  
Gerard Marshall Raj ◽  
Mukta Wyawahare
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Sglt2 Inhibitor ◽  
Therapeutic Application ◽  
Glucose Lowering ◽  
Reduced Ejection Fraction ◽  
Beneficial Effects

Dapagliflozin, an SGLT2 inhibitor used in the management of Type 2 diabetes mellitus, has been recently approved for the control of worsening cardiovascular events, including deaths and hospitalizations, in adults with heart failure with reduced ejection fraction. Previously, canagliflozin had a label change with regards to its additional usage in the reduction of risk of hospitalization for heart failure in patients with both Type 2 diabetes mellitus and diabetic nephropathy with albuminuria. On the other hand, the therapeutic application of empagliflozin and ertugliflozin in heart failure is yet to be delineated comprehensively. The beneficial effects of these SGLT2 inhibitors, dapagliflozin in particular, in heart failure are found to be independent of neither the glucose-lowering nor the SGLT2 inhibiting effects.

scholarly journals The Mystery of Acidosis

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A402-A402
Author(s):  
Syeda Naqvi ◽  
Apurwa Prasad ◽  
Sabah Syed
Keyword(s):  
Abdominal Pain ◽  
Chart Review ◽  
Glucose Transporter ◽  
Sinus Tachycardia ◽  
Oral Glucose ◽  
Glucose Lowering ◽  
Glucose Transporter 2 ◽  
History Of ◽  
Lab Test

Abstract We present a case of 30-year-old female with past medical history of Type 2 DM, Thyroid nodule and asymptomatic cholelithiasis who presented to ED with abdominal pain, vomiting and sinus tachycardia of 120’s for past one day. She had generalized abdominal pain, not relieved by pain killers. Her lab test includes normal blood count, glucose 150mg/dl, anion gap of 20, metabolic acidosis. Her ultrasound abdomen showed cholelithiasis with no biliary sludge formation. Given her acidosis and severe abdominal pain she was started on Zosyn and underwent cholecystectomy. Her abdominal pain and sinus tachycardia did not resolve till day 3 of admission. Urine was positive for ketones. On chart review, it was found that she started taking sodium glucose transporter 2 inhibitor (SGLT-2 inhibitor), Canagliflozin. She was given IV fluids and insulin. She improved and her tachycardia resolved. Euglycemic acidosis is a rare phenomenon but frequently misdiagnosed. This case emphasizes on importance of side effects of oral glucose lowering agents. SGLT-2 inhibitors can cause lipolysis and ketosis while maintaining euglycemia. Prompt clinical judgement is needed to prevent misdiagnosis. Also, patients should be educated about aggravating factors like stress, dehydration or other severe illnesses.

scholarly journals Effects of GLP-1RA and SGLT2i, Alone or in Combination, on Mouse Models of Type 2 Diabetes Representing Different Disease Stages

2021 ◽  
Vol 22 (21) ◽  
pp. 11463
Author(s):  
Masao Koike ◽  
Hitoki Saito ◽  
Genta Kohno ◽  
Masahiro Takubo ◽  
Kentaro Watanabe ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glycemic Control ◽  
Fatty Liver ◽  
Glucose Transporter ◽  
Hepatic Lipid Accumulation ◽  
Beneficial Effects ◽  
Glucose Transporter 2 ◽  
Combined Use ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 receptor agonist (GLP-1RA) and sodium-dependent glucose transporter 2 inhibitor (SGLT2i), in addition to lowering glucose, have pleiotropic effects on the heart, kidneys, and liver. These drugs have thus come into widespread use for treating type 2 diabetes (T2DM). However, mechanistic comparisons and effects of combining these drugs have not been adequately studied. Employing diet-induced obese (DIO) mice and db/db mice as models of the early and advanced stages of T2DM, we evaluated effects of single or combined use of liraglutide (a GLP-1RA) and ipragliflozin (a SGLT2i). Treatments with liraglutide and/or ipragliflozin for 28 days improved glycemic control and reduced hepatic lipid accumulation similarly in DIO mice. In contrast, in db/db mice, despite similar favorable effects on fatty liver, liraglutide exerted no beneficial effects on glycemic control. Improved glycemic control in db/db mice treated with ipragliflozin was accompanied by increased pancreatic β-cell area and insulin content, both of which tended to rise further when ipragliflozin was combined with liraglutide. Our data suggest that liraglutide is more efficient at an earlier stage and ipragliflozin can be effective in both stages. In addition, their combined use is a potential option for treating advanced stage diabetes with fatty liver disease.

scholarly journals Advances in the management of diabetes: therapies for type 2 diabetes

2020 ◽  
Vol 96 (1140) ◽  
pp. 610-618
Author(s):  
Jovanna Tsoutsouki ◽  
Wunna Wunna ◽  
Aisha Chowdhury ◽  
Tahseen Ahmad Chowdhury
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Transporter ◽  
Microvascular Complications ◽  
General Physician ◽  
Beneficial Effects ◽  
Glucose Transporter 2 ◽  
Current State ◽  
Glucagon Like Peptide 1 ◽  
Dipeptidylpeptidase 4

The incidence of type 2 diabetes is rapidly rising worldwide leading to an increasing burden of cardiovascular and microvascular complications. The aim of treatment of the condition is to improve quality of life and reduce such complications. To this end, improvement in glucose control remains an important consideration. In recent years, important therapeutic advances have occurred in the management of hyperglycaemia in people with type 2 diabetes. These include the use of dipeptidylpeptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists and sodium glucose transporter-2 inhibitors. The latter two classes appear to have some specific beneficial effects on cardiovascular and renal outcomes, independent of their antihyperglycaemic effects. This review aims to outline the current state of diagnosis and management of diabetes for the general physician, with a particular focus on new therapeutic agents for management of glucose in patients with type 2 diabetes.

Efficacy and cardiovascular safety of Thiazolidinediones

2020 ◽  
Vol 15 ◽  
Author(s):  
Raveendran Arkiath Veettil ◽  
Cornelius James Fernandez ◽  
Koshy Jacob
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Glucose Transporter ◽  
Cell Function ◽  
Cardiovascular Safety ◽  
Cardiovascular Outcome Trials ◽  
Glucose Transporter 2 ◽  
Insulin Sensitizers

: Type 2 diabetes mellitus (T2DM) is characterized by a progressive beta cell dysfunction in the setting of peripheral insulin resistance. Insulin resistance in subjects with type 2 diabetes and metabolic syndrome is primarily caused by an ectopic fat accumulation in liver and skeletal muscle. Insulin sensitizers are particularly important in the management of T2DM. Though, thiazolidinediones (TZDs) are principally insulin sensitizers, they possess an ability to preserve pancreatic β-cell function and thereby exhibit durable glycemic control. Cardiovascular outcome trials (CVOTs) have shown that Glucagon-like-peptide 1 receptor agonists (GLP-1 RAs) and sodium glucose transporter-2 inhibitors (SGLT2i) have proven cardiovascular safety. In this era of CVOTs, drugs with proven cardiovascular (CV) safety are often preferred in patients with preexisting cardiovascular disease or at risk of cardiovascular disease. In this review, we will describe the three available drugs belonging to the TZD family, with special emphasis on their efficacy and CV safety.

scholarly journals Renoprotective Effects of DPP-4 Inhibitors

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 246
Author(s):  
Daiji Kawanami ◽  
Yuichi Takashi ◽  
Hiroyuki Takahashi ◽  
Ryoko Motonaga ◽  
Makito Tanabe
Keyword(s):  
Diabetic Kidney Disease ◽  
Experimental Studies ◽  
Review Article ◽  
Glucose Lowering ◽  
Beneficial Effects ◽  
Glucose Levels ◽  
Membrane Bound ◽  
Stage Renal Disease ◽  
End Stage

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) worldwide. Dipeptidyl peptidase (DPP)-4 inhibitors are widely used in the treatment of patients with type 2 diabetes (T2D). DPP-4 inhibitors reduce glucose levels by inhibiting degradation of incretins. DPP-4 is a ubiquitous protein with exopeptidase activity that exists in cell membrane-bound and soluble forms. It has been shown that an increased renal DPP-4 activity is associated with the development of DKD. A series of clinical and experimental studies showed that DPP-4 inhibitors have beneficial effects on DKD, independent of their glucose-lowering abilities, which are mediated by anti-fibrotic, anti-inflammatory, and anti-oxidative stress properties. In this review article, we highlight the current understanding of the clinical efficacy and the mechanisms underlying renoprotection by DPP-4 inhibitors under diabetic conditions.

scholarly journals Microalbuminuria as an independent risk factor for heart failure in the elderly patients with type 2 diabetes mellitus

2020 ◽  
Vol 49 (2) ◽  
Author(s):  
Enisa Karić ◽  
Zumreta Kušljugić ◽  
Enisa Ramić ◽  
Olivera Batić- Mujanović ◽  
Amila Bajraktarević ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Risk Factor ◽  
Diabetes Mellitus Type 2 ◽  
Independent Risk Factor ◽  
The Elderly ◽  
Diabetes Mellitus Type ◽  
Patients With Diabetes

Introduction:The study evaluated of microalbuminuria as a predictor of heart failure in patients with diabetes mellitus type 2.Materials and methods:The prospective study conducted in a period of time from 01-Feb-2007 to 01-Feb-2010.The study included 100 patients with type 2 diabetes, who had diabetes longer than 5 years. All subjects (average age 66 ± 10 years, 33% male, 67% female) were tested for the presence of microalbuminuria, and 50 patients had microalbuminuria. The second group comprised 50 patients without of microalbuminuria with diabetes mellitus type 2.Results:In the patients with microalbuminuria and diabetes mellitus were found 22% of heart failure and 6% in the second group. Average time to the occurance of heart failure in the first group was 32,5 months, in the second group was 35,3 months.Conclusions:The results show that microalbuminuria is an independent risk factor for heart failure in patients with diabetes mellitus type 2 and microalbuminuria. Patients without microalbuminuria had 3,7 less likely to development heart failure compared to patients with microalbuminuria and diabetes mellitus.

scholarly journals How glucagon-like peptide 1 receptor agonists work

2021 ◽  
Author(s):  
Christine Rode Andreasen ◽  
Andreas Andersen ◽  
Filip Krag Knop ◽  
Tina Vilsbøll
Keyword(s):  
Body Weight ◽  
Therapeutic Potential ◽  
Clinical Effects ◽  
Glucose Lowering ◽  
Receptor Agonists ◽  
Reduce Body Weight ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Clinical Utilisation

Recent years, glucagon-like peptide 1 receptor agonists (GLP-1RAs) have become central in the treatment of type 2 diabetes (T2D). In addition to their glucose-lowering properties with low risk of hypoglycaemia, GLP-1RAs reduce body weight and show promising results in reducing cardiovascular risk and renal complications in high-risk individuals with T2D. These findings have changed guidelines on T2D management over the last years, and GLP-1RAs are now widely used in overweight patients with T2D as well as in patients with T2D and cardiovascular disease regardless of glycaemic control. The currently available GLP-1RAs have different pharmacokinetic profiles and differ in their ability to improve glycaemia, reduce body weight and in their cardio- and renal protective potentials. Understanding how these agents work, including insights into their pleiotropic effects on T2D pathophysiology, may improve their clinical utilisation and be useful for exploring other indications such as non-alcoholic steatohepatitis and neurodegenerative disorders. In this review, we provide an overview of approved GLP-1RAs, their clinical effects and mode of actions, and we offer insights into the potential of GLP-1RAs for other indications than T2D. Finally, we will discuss the emerging data and therapeutic potential of using GLP-1RAs in combinations with other receptor agonists.

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