SGLT-2 Inhibitors in Development for Type 2 Diabetes Treatment

Bhartia, Mithun; Tahrani, Abd A; Barnett, Anthony

doi:10.1900/rds.2011.8.348

Cited by 28 publications

(17 citation statements)

References 20 publications

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“…These agents are systemically absorbed following ingestion, and act at the kidney to lower the threshold for urinary loss of glucose [37]. This class of agents is early in development, and neither preclinical studies nor clinical studies addressing effects on vascular function have been published to date.…”

Section: Therapies That Target the Endotheliummentioning

confidence: 99%

The vascular endothelium in diabetes—a therapeutic target?

Mather

2013

Rev Endocr Metab Disord

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Insulin resistance affects the vascular endothelium, and contributes to systemic insulin resistance by directly impairing the actions of insulin to redistribute blood flow as part of its normal actions driving muscle glucose uptake. Impaired vascular function is a component of the insulin resistance syndrome, and is a feature of type 2 diabetes. On this basis, the vascular endothelium has emerged as a therapeutic target where the intent is to improve systemic metabolic state by improving vascular function. We review the available literature presenting studies in humans, evaluating the effects of metabolically targeted and vascular targeted therapies on insulin action and systemic metabolism. Therapies that improve systemic insulin resistance exert strong concurrent effects to improve vascular function and vascular insulin action. RAS-acting agents and statins have widely recognized beneficial effects on vascular function but have not uniformly produced the hoped-for metabolic benefits. These observations support the notion that systemic metabolic benefits can arise from therapies targeted at the endothelium, but improving vascular insulin action does not result from all treatments that improve endothelium-dependent vasodilation. A better understanding of the mechanisms of insulin's actions in the vascular wall will advance our understanding of the specificity of these responses, and allow us to better target the vasculature for metabolic benefits.

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Section: Therapies That Target the Endotheliummentioning

confidence: 99%

The vascular endothelium in diabetes—a therapeutic target?

Mather

2013

Rev Endocr Metab Disord

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“…[1011] All these drugs are effective at the beginning, but the treatment effect declines with time and is ineffective in long term because the beta cell dysfunction progressively increases and this requires combination therapy and insulin. [12] Common side effects associated with the use of conventional oral antidiabetic drugs (OADs) include hypoglycemia, weight gain, edema, and CV adverse effects. [121314] The sustained glycemic control over the period is not available with most of other antidiabetic agents which could be due to natural progression of disease, self-monitoring for glucose, and the administration by use of injections.…”

Section: Unmet Needs From Current Antidiabetic Agentsmentioning

confidence: 99%

Sodium glucose co-transporter-2 inhibitor: Benefits beyond glycemic control

Baruah¹,

Makkar

Ghatnatti

et al. 2019

Indian J Endocr Metab

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Type 2 diabetes mellitus (T2DM) is a family of metabolic disorders characterized by hyperglycemia as a consequence of abnormalities in insulin secretion and insulin sensitivity. It affects hundreds of millions of people worldwide and leads to increased morbidity, compromised quality of life, higher mortality sodium glucose co-transporter 2 (SGLT2) inhibitors, a new class of oral antidiabetic drugs, have garnered considerable attention in the recent past and are considered potential first-line candidates for the management of T2DM. This review outlines the evidence-based therapeutic efficacy, safety, limitations, and advantages of SGLT2 inhibitors in the management of T2DM. SGLT2 inhibitors work by preventing the kidneys from reabsorbing glucose back into the blood, leading to increase in excretion of glucose through urine, thereby lowering hyperglycemia. Treatment with SGLT2 inhibitors improves A1C levels, reduces blood pressure and body weight, and is overall well tolerated by patients with T2DM. However, additional data on long-term cardiovascular safety are still needed. Characteristic adverse events include mild genital - urinary tract infection more commonly seen in women than in men, but serious infection is uncommon. Their use should be exercised with extra caution in patients suffering from renal impairment. Further, advancing to dual/triple combinational therapies with SGLT2 inhibitors and existing oral antidiabetic options may prove to be a breakthrough in the management of T2DM.

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“…In 2011, an FDA advisory panel expressed concern regarding a reported increased incidence of breast cancer in patients treated with the SGLT-2 inhibitor dapagliflozin. (50) SGLT-2 inhibitor treatment has also been associated with an increased risk of fungal urinary tract infection. (49)…”

Section: Sodium Glucose Co-transporter 2 Inhibitorsmentioning

confidence: 99%

Cardiovascular effects of antidiabetic agents: focus on blood pressure effects of incretin-based therapies

Brown

2012

Journal of the American Society of Hypertension

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Hyperglycemia is associated with increased risk of cardiovascular disease. Nevertheless, results of large clinical trials suggest that tight glucose control does not reduce the risk of macrovascular cardiovascular events in type 2 diabetes mellitus and may cause harm. This may reflect the adverse consequences of increased hypoglycemia or the adverse effects of many anti-diabetic agents on weight gain. The consequences of intensive therapy may also depend on the mechanism of the anti-diabetic agent(s) used to achieve tight control. Metformin, an anti-diabetic agent that reduces weight and activates AMP-activated protein kinase, reduces risk of cardiovascular events in overweight diabetics. In contrast, the thiazolidinedione rosiglitazone increases cardiovascular risk. Sulfonylureas may increase the risk of cardiovascular events through effects on the SUR1 of the cardiac KATP channel. Stable analogues of glucagon-like peptide-1 reduce body weight and blood pressure, and have favorable effects on ischemia following reperfusion in animal models. The dipeptidyl peptidase IV inhibitors prevent the breakdown of GLP-1 and GIP, but also decrease the degradation of several vasoactive peptides. Dipeptidyl peptidase IV inhibitors have favorable effects in animal models of ischemia/reperfusion. They have been reported both to decrease and to increase blood pressure. Clinical trials will address the effect of the incretin-based agents on macrovascular cardiovascular events.

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SGLT-2 Inhibitors in Development for Type 2 Diabetes Treatment

Cited by 28 publications

References 20 publications

The vascular endothelium in diabetes—a therapeutic target?

The vascular endothelium in diabetes—a therapeutic target?

Sodium glucose co-transporter-2 inhibitor: Benefits beyond glycemic control

Cardiovascular effects of antidiabetic agents: focus on blood pressure effects of incretin-based therapies

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