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Sodium-glucose Cotransporter-2 Inhibitors: Moving Beyond the Glycemic Treatment Goal.

ABSTRACT: Revelations of the multifactorial pathogenesis of type 2 diabetes mellitus (T2DM) that extend beyond the role of insulin and glucose utilization have been crucial in redefining the treatment paradigm. The focus of treatment is currently directed towards achieving wide-ranging targets encompassing the management of cardiovascular comorbidities that have been evidenced as indispensable aspects of T2DM. While most currently prescribed antihyperglycemic agents have little or no effect on reducing cardiovascular risks, some have been associated with undesirable effects on common risk factors such as weight gain and cardiovascular sequelae. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are newer additions to the array of therapeutic agents for T2DM that have demonstrated robust glycemic control as mono and add-on therapies. Their unique renal mode of action, independent of insulin modulation, confers complementary metabolic benefits. By virtue of these effects, SGLT2i may have a distinct role in the revised treatment recommendations by established working groups such as the American Diabetes Association and the American Association of Clinical Endocrinologists that advocate a more comprehensive management of T2DM, not restricting to glycemic targets. The current review gives an overview of the changing treatment needs for T2DM and discusses the nonglycemic effects of SGLT2i. It provides an updated summary on the efficacy of canagliflozin, dapagliflozin, and empagliflozin in promoting weight loss, stabilizing blood pressure, and other favorable metabolic effects.

SUBMITTER: Gupta V

PROVIDER: S-EPMC5729683 | biostudies-other | 2017 Nov-Dec

REPOSITORIES: biostudies-other

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Sodium-glucose Cotransporter-2 Inhibitors: Moving Beyond the Glycemic Treatment Goal.

Gupta Vishal V Canovatchel William W Lokesh B N BN Santani Ravi R Garodia Nishant N

Indian journal of endocrinology and metabolism 20171101 6

Revelations of the multifactorial pathogenesis of type 2 diabetes mellitus (T2DM) that extend beyond the role of insulin and glucose utilization have been crucial in redefining the treatment paradigm. The focus of treatment is currently directed towards achieving wide-ranging targets encompassing the management of cardiovascular comorbidities that have been evidenced as indispensable aspects of T2DM. While most currently prescribed antihyperglycemic agents have little or no effect on reducing ca ...[more]

PMID: 29285458

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Project description:Despite the availability of established treatments, heart failure (HF) is associated with a poor prognosis and its management is suboptimal, highlighting the need for new options for treatment and prevention. Patients with type 2 diabetes (T2D) often experience cardiovascular (CV) complications, with HF being one of the most frequent. Consequently, several CV outcome trials have focused on glucose-lowering therapies and their impact on CV outcomes. An established treatment for T2D, sodium-glucose cotransporter-2 inhibitors (SGLT-2is; canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin) have demonstrated beneficial effects on CV outcomes in long-term studies of patients with T2D with established CV disease and/or a broad range of CV risk factors. Recent studies have extended these findings to patients with HF, with and without T2D, finding that SGLT-2is (particularly dapagliflozin and empagliflozin) are effective therapeutic interventions for the treatment and prevention of HF. This narrative review article discusses the use of SGLT-2is in the treatment and prevention of HF in patients with and without T2D. Dapagliflozin was the first SGLT-2i to receive US Food and Drug Administration (FDA) approval for treatment of HF, to reduce the risk of CV death and hospitalization for HF in adults with HF with reduced ejection fraction (HFrEF) with and without T2D. Recently, the FDA also approved empagliflozin for this indication. Given the new HFrEF indications for dapagliflozin and empagliflozin, and the likelihood of similar approvals for other SGLT-2is, cardiology guidelines are beginning to integrate SGLT-2is into a standard-of-care treatment regimen for patients with HFrEF. The utility of SGLT-2is in HF with preserved EF (HFpEF) shows promise based on data from the EMPEROR-Preserved study of empagliflozin in patients with HFpEF. Further clinical trial evidence may lead to more widespread use and further integration of SGLT-2is into standard-of-care regimens for the treatment and management of HF in patients with and without T2D.

Dataset Information

Sodium-glucose Cotransporter-2 Inhibitors: Moving Beyond the Glycemic Treatment Goal.

Publications

Sodium-glucose Cotransporter-2 Inhibitors: Moving Beyond the Glycemic Treatment Goal.

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