Tofogliflozin decreases body fat mass and improves peripheral insulin resistance

Matsuba, Ren; Matsuba, Ikuro; Shimokawa, Mototsugu; Nagai, Yoshio; Tanaka, Yasushi

doi:10.1111/dom.13211

Cited by 34 publications

(35 citation statements)

References 18 publications

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“…Previously, SGLT2 inhibitor administration was shown to result in changes in body composition through the reduction of body fat mass ( 4 ). Thus, SGLT2 inhibitors improve not only hyperglycemia via the promotion of urinary glucose excretion, but also obesity via the promotion of lipolysis and prevention of lipogenesis ( 12 ).…”

Section: Discussionmentioning

confidence: 99%

“…Recent clinical trials have shown the various beneficial effects of SGLT2 inhibitors, including reductions in the risk of cardiovascular events and mortality in diabetes mellitus ( 1 , 2 ). SGLT2 inhibitors exert glucose-lowering effects, improving insulin sensitivity through the changes in the body composition over long-term treatment ( 3 , 4 ).…”

Section: Introductionmentioning

confidence: 99%

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Improvement of skeletal muscle insulin sensitivity by 1 week of SGLT2 inhibitor use

Goto

Otsuka

Ashida

et al. 2020

Endocrine Connections

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Background and Aims: It is currently unclear whether sodium–glucose co-transporter 2 (SGLT2) inhibitor administration can improve the insulin sensitivity as well as rapidly reduce plasma glucose concentrations in humans during the early phase of treatment initiation. This study aimed to investigate the effect of SGLT2 inhibitor on insulin sensitivity in the early phase of treatment initiation. Methods and Results This single-center, open label, and single-arm prospective study recruited 20 patients (14 men) with type 2 diabetes mellitus (T2DM). We examined the patients’ metabolic parameters before and 1 week after SGLT2 inhibitor (10 mg/day of empagliflozin) administration. The glucose infusion rate (GIR) was evaluated using the euglycemic hyperinsulinemic glucose clamp technique. Changes in laboratory and anthropometric parameters before and after SGLT2 inhibitor administration were analyzed according to the change in the GIR. The BMI, body fat amount, skeletal muscle amount, systolic blood pressure, and triglyceride level significantly decreased along with the treatment, while urinary glucose level and log GIR value significantly increased. Notably, changes in the GIR after SGLT2 inhibitor administration, which indicated improvement in peripheral insulin sensitivity, were negatively correlated with T2DM duration and positively with reduction in fluctuation of daily plasma glucose profiles before and after treatment. Conclusion SGLT2 inhibitor improved insulin sensitivity in the skeletal muscle independent of anthropometric changes. Patients with short duration of T2DM and insulin resistance can be good candidates for short-term SGLT2 inhibitor administration to improve insulin sensitivity in the skeletal muscle.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Improvement of skeletal muscle insulin sensitivity by 1 week of SGLT2 inhibitor use

Goto

Otsuka

Ashida

et al. 2020

Endocrine Connections

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“…We repeatedly evaluated the HOMA-IR to determine changes in insulin resistance. Although insulin sensitivity should ideally be precisely evaluated using the glucose clamp procedure [26,27], this method is impractical for the long-term assessment of large numbers of patients. Nevertheless, the glucose clamp procedure is needed to accurately evaluate the ability of omarigliptin to decrease insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

Omarigliptin decreases inflammation and insulin resistance in a pleiotropic manner in patients with type 2 diabetes

Hattori

2020

Diabetol Metab Syndr

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Background: Omarigliptin is a potent, selective, oral dipeptidyl peptidase 4 (DPP4) inhibitor with a half-life that allows weekly dosing. Inflammation or insulin resistance might be pathological mediators of cardiovascular events in patients with type 2 diabetes. Methods: Whether omarigliptin has anti-inflammatory effects that result in decreased levels of high-sensitivity C-reactive protein (hsCRP) and anti-insulin resistance effects that decrease levels of homeostatic model assessment of insulin resistance (HOMA-IR) were investigated. Patients were allocated to continue with daily DPP4 inhibitors (control, n = 28) or to switch from daily DPP4 inhibitors to weekly omarigliptin (omarigliptin, n = 56). Fasting blood and urine samples were collected before, and every 3 months after intervention for 1 year. Results: Omarigliptin tended to elicit reductions in fasting blood glucose (FBG), LDL-cholesterol, triglyceride, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GTP), the urinary albumin-to-creatinine ratio (ACR) with logarithmic transformation (log ACR), and systolic and diastolic blood pressure, but the differences did not reach statistical significance compared with control. Values for HDL-cholesterol tended to increase, but also did not reach statistical significance compared with control. Omarigliptin significantly decreased HOMA-IR, remnant-like particle cholesterol (RLP-C), and hsCRP with logarithmic transformation (log hsCRP) compared with control. However, omarigliptin did not affect hemoglobin A1c (HbA1c), body mass index (BMI), and estimated glomerular filtration rates (eGFR). Conclusion: Omarigliptin decreased inflammation and insulin resistance without affecting HbA1c or BMI. Although how DPP4 inhibitors affect cardiovascular (CV) outcomes remains uncertain, omarigliptin might confer CV benefits at least in part, via pleiotropic anti-inflammatory or anti-insulin resistance effects. Trial registration UMIN Clinical Registry (UMIN000029288). Registered 22 September, 2017, https ://uploa d.umin.ac.jp/ UMIN0 00029 288

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“…It also improves the function of pancreatic β cells and kidney and has beneficial effects on lipid metabolism, especially when the patient consumes the appropriate dietary carbohydrate composition (Ito et al, ). Tofogliflozin reduces body fat mass leading to improvement in insulin sensitivity and peripheral glucose uptake (Matsuba, Matsuba, Shimokawa, Nagai, & Tanaka, ). Renal function does not affect the pharmacokinetics of tofogliflozin; hence, dose adjustment is not required for T2DM patients with renal disorders (Ikeda et al, ).…”

Section: Phlorizinmentioning

confidence: 99%

Natural products with SGLT2 inhibitory activity: Possibilities of application for the treatment of diabetes

Moradi‐Marjaneh

Paseban

Sahebkar

2019

Phytotherapy Research

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Diabetes mellitus currently affects as many as 400 million people worldwide, creating a heavy economic burden and stretching health care resources. A dysfunction of glucose homeostasis underlies the disease. Despite advances in the treatment of diabetes, many patients still suffer from complications and side effects; hence, development of more effective treatments for diabetes is still desirable. SGLT2 is the principle cotransporter involved in glucose reabsorption in the kidney. SGLT2 inhibition reduces glucose reabsorption by the kidney and ameliorates plasma glucose concentration. The interest in natural products that can be used for the inhibition of SGLT2 is growing. The flavonoid phlorizin, which can be isolated from the bark of apple trees, has been used as lead structure due to its inhibitory activity of SGLT1 and SGLT2. Some phlorizin-derived synthetic compounds, including canagliflozin, dapagliflozin, empagliflozin, ipragliflozin, and ertugliflozin, are approved by the food and drug administration to treat type 2 diabetes mellitus (T2DM), whereas others are under clinical trials investigation. In addition, other natural product-derived compounds have been investigated for their ability to improve blood glucose control.The present review summarizes the natural products with SGLT2 inhibitory activity, and the synthetic compounds obtained from them, and discusses their application for the treatment of diabetes.

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Tofogliflozin decreases body fat mass and improves peripheral insulin resistance

Cited by 34 publications

References 18 publications

Improvement of skeletal muscle insulin sensitivity by 1 week of SGLT2 inhibitor use

Improvement of skeletal muscle insulin sensitivity by 1 week of SGLT2 inhibitor use

Omarigliptin decreases inflammation and insulin resistance in a pleiotropic manner in patients with type 2 diabetes

Natural products with SGLT2 inhibitory activity: Possibilities of application for the treatment of diabetes

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