Efficacy of Body Weight Reduction on the SGLT2 Inhibitor in People with Type 2 Diabetes Mellitus

Cho, Hyun A; Jung, Young Lee; Lee, Yong Hoon; Lee, Yu Chang; Lee, Jung Eun; Lee, Sol Jae; Jeong, Su Jin; Kim, Chong Hwa

doi:10.7570/jomes.2017.26.2.107

Cited by 7 publications

(8 citation statements)

References 19 publications

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“…In a previous study, dapagliflozin treatment for 6 months reduced whole body fat mass by 1.48 kg and WC by 1.52 cm in European patients (baseline BMI, 31.9 kg/m 2 ) with T2D inadequately controlled with metformin [26]. In a previous study with Koreans with T2D, the body weight was decreased significantly by 2.7±2.0 kg after a 12-month treatment with dapagliflozin and metformin with sulfonylurea, or DPP4 inhibitors [27]. In our Korean patients (baseline BMI, 27.4 kg/m 2 ), whole body fat mass decreased by 2.3 kg and WC decreased by 1.8 cm.…”

Section: Discussionmentioning

confidence: 92%

Glycemic Efficacy and Metabolic Consequences of an Empagliflozin Add-on versus Conventional Dose-Increasing Strategy in Patients with Type 2 Diabetes Inadequately Controlled by Metformin and Sulfonylurea

et al. 2020

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Background: We assessed the glucose-lowering efficacy of adding empagliflozin versus dose escalating existing medications in patients with uncontrolled type 2 diabetes (T2D). Methods: This was a 6-month retrospective case-control study in subjects with uncontrolled T2D (glycated hemoglobin [HbA1c] >7%) on conventional treatment. The study group started add-on therapy with empagliflozin (10 mg once a day) while the control group was up-titrated with existing medication, using either monotherapy or a combination of metformin, sulfonylurea, and a dipeptidyl peptidase-4 inhibitor. The primary endpoints included changes in HbA1c, fasting plasma glucose (FPG), and 2-hour postprandial glucose (PP2) levels. Secondary outcomes included changes in body composition, body mass index (BMI), and serum ketone bodies, and urinary excretion of sodium, potassium, chlorine, calcium, phosphorus, and glucose. Results: After treatment, the reduction in HbA1c was significantly greater in the empagliflozin group than in controls (from 8.6%± 1.6% to 7.6%±1.5% vs. 8.5%±1.1% to 8.1%±1.1%; P<0.01). Similar patterns were found in FPG and PP2 levels. Empagliflozin decreased systolic and diastolic blood pressure, triglycerides, and alanine and aspartate aminotransferase levels. Body weight, BMI, waist circumference, fat mass, and abdominal visceral fat area decreased significantly while lean body mass was maintained. Total ketones, β-hydroxybutyrate, and acetoacetate levels increased significantly after empagliflozin. Conclusion: In addition to glucose lowering, an empagliflozin add-on regimen decreased blood pressure and body fat, and improved metabolic profiles significantly. Empagliflozin add-on is superior to dose escalation in patients with T2D who have inadequate glycemic control on standard medications.

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Section: Discussionmentioning

confidence: 92%

Glycemic Efficacy and Metabolic Consequences of an Empagliflozin Add-on versus Conventional Dose-Increasing Strategy in Patients with Type 2 Diabetes Inadequately Controlled by Metformin and Sulfonylurea

et al. 2020

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“…Body weight, A1C, and systolic BP are the various parameters used to determine the responders/non-responders to SGLT2i treatment in various studies [ 40 – 43 ]. In a post hoc analysis of two double-blind RCTs, patients in the SGLT2i treatment arm who had a 12-week A1C or systolic BP change lower than the median were considered as an A1C or systolic BP responder; a non-responder was defined as a 12-week A1C or systolic BP change on or above the median [ 40 ].…”

Section: Sglt2i and Diabetesmentioning

confidence: 99%

“…In a post hoc analysis of two double-blind RCTs, patients in the SGLT2i treatment arm who had a 12-week A1C or systolic BP change lower than the median were considered as an A1C or systolic BP responder; a non-responder was defined as a 12-week A1C or systolic BP change on or above the median [ 40 ]. Similarly, in a retrospective study, SGLT2i-treated patients who had ≥ 5% body weight reduction were classified as responders and those with < 5% body weight reduction were classified as non-responders [ 43 ]. Moreover, baseline fasting C-peptide level was the important factor influencing change in body weight; it was found to be higher in the responder group than in the non-responder group (3.25 ± 1.07 vs 2.62 ± 1.02 ng/mL, P = 0.023) [ 43 ].…”

Section: Sglt2i and Diabetesmentioning

confidence: 99%

“…Similarly, in a retrospective study, SGLT2i-treated patients who had ≥ 5% body weight reduction were classified as responders and those with < 5% body weight reduction were classified as non-responders [ 43 ]. Moreover, baseline fasting C-peptide level was the important factor influencing change in body weight; it was found to be higher in the responder group than in the non-responder group (3.25 ± 1.07 vs 2.62 ± 1.02 ng/mL, P = 0.023) [ 43 ]. …”

Section: Sglt2i and Diabetesmentioning

confidence: 99%

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Evidence-Based Consensus on Positioning of SGLT2i in Type 2 Diabetes Mellitus in Indians

Singh

Unnikrishnan²,

Zargar³

et al. 2019

Diabetes Ther

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The current diabetes management strategies not only aim at controlling glycaemic parameters but also necessitate continuous medical care along with multifactorial risk reduction through a comprehensive management concept. The sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a group of evolving antidiabetic agents that have the potential to play a pivotal role in the comprehensive management of patients with diabetes due to their diverse beneficial effects. SGLT2i provide moderate glycaemic control, considerable body weight and blood pressure reduction, and thus have the ability to lower the risk of macrovascular and microvascular complications. Some of the unique characteristics associated with SGLT2i, such as reduction in body weight (more visceral fat mass loss than subcutaneous fat loss), reduction in insulin resistance and improvement in β-cell function, as measured by homeostatic model assessment-β (HOMA-β) could be potentially beneficial and help in overcoming some of the challenges faced by Indian patients with diabetes. In addition, a patient-centric approach with individualised treatment during SGLT2i therapy is inevitable in order to reduce diabetic complications and improve quality of life. Despite their broad benefits profile, the risk of genital tract infections, volume depletion, amputations and diabetic ketoacidosis associated with SGLT2i should be carefully monitored. In this compendium, we systematically reviewed the literature from Medline, Cochrane Library, and other relevant databases and attempted to provide evidence-based recommendations for the positioning of SGLT2i in the management of diabetes in the Indian population. Funding : AstraZeneca Pharma India Limited.

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“…The switch of preferred substrate from glucose to ketone bodies by SGLT-2 inhibitors is of particular interest because ketone bodies can cross the blood–brain barrier and are the normal metabolic substrate for neurons [ 24 ]. Given that these phenotypic changes mirror the effects of FGF21, FGF21 would be a good agent to be used with SGLT-2 inhibitors [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of Fibroblast Growth Factor 21 on the Development of Atheromatous Plaque and Lipid Metabolic Profiles in an Atherosclerosis-Prone Mouse Model

Maeng

Lee

Bae

et al. 2020

IJMS

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Fibroblast growth factor 21 (FGF21) is a hormonal regulator of lipid and glucose metabolism. We aimed to investigate the effect of an FGF21 analogue (LY2405319) on the development of atherosclerosis and its associated parameters. ApoE−/− mice were fed an atherogenic diet for 14 weeks and were randomly assigned to control (saline) or FGF21 (0.1 mg/kg) treatment group (n = 10/group) for 5 weeks. Plaque size in the aortic arch/valve areas and cardiovascular risk markers were evaluated in blood and tissues. The effects of FGF21 on various atherogenesis-related pathways were also assessed. Atherosclerotic plaque areas in the aortic arch/valve were significantly smaller in the FGF21 group than in controls after treatment. FGF21 significantly decreased body weight and glucose concentrations, and increased circulating adiponectin levels. FGF21 treatment alleviated insulin resistance and decreased circulating concentrations of triglycerides, which were significantly correlated with plaque size. FGF21 treatment reduced lipid droplets in the liver and decreased fat cell size and inflammatory cell infiltration in the abdominal visceral fat compared with the control group. The monocyte chemoattractant protein-1 levels were decreased and β-hydroxybutyrate levels were increased by FGF21 treatment. Uncoupling protein 1 expression in subcutaneous fat was greater and fat cell size in brown fat was smaller in the FGF21 group compared with controls. Administration of FGF21 showed anti-atherosclerotic effects in atherosclerosis-prone mice and exerted beneficial effects on critical atherosclerosis pathways. Improvements in inflammation and insulin resistance seem to be mechanisms involved in the mitigation of atherosclerosis by FGF21 therapy.

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Efficacy of Body Weight Reduction on the SGLT2 Inhibitor in People with Type 2 Diabetes Mellitus

Cited by 7 publications

References 19 publications

Glycemic Efficacy and Metabolic Consequences of an Empagliflozin Add-on versus Conventional Dose-Increasing Strategy in Patients with Type 2 Diabetes Inadequately Controlled by Metformin and Sulfonylurea

Glycemic Efficacy and Metabolic Consequences of an Empagliflozin Add-on versus Conventional Dose-Increasing Strategy in Patients with Type 2 Diabetes Inadequately Controlled by Metformin and Sulfonylurea

Evidence-Based Consensus on Positioning of SGLT2i in Type 2 Diabetes Mellitus in Indians

Effect of Fibroblast Growth Factor 21 on the Development of Atheromatous Plaque and Lipid Metabolic Profiles in an Atherosclerosis-Prone Mouse Model

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