Use of SGLT-2 Inhibitors in Patients with Type 2 Diabetes Mellitus and Abdominal Obesity: An Asian Perspective and Expert Recommendations

Sheu, Wayne Huey Herng; Chan, Siew Pheng; Matawaran, Bien J.; Deerochanawong, Chaicharn; Mithal, Ambrish; Chan, Juliana C.N.; Suastika, Ketut; Khoo, Chin Meng; Nguyen, Huu Man; Ji, Linong; Luk, Andrea; Yoon, Kun Ho

doi:10.4093/dmj.2019.0208

Cited by 38 publications

(41 citation statements)

References 142 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, glucagon secretion increases after administration of SGLT2 inhibitors, possibly because of rapid loss of glucose from the body [ 23 , 24 ]. Elevated plasma glucagon level also contributes to promoting lipolysis and reducing liver fat and visceral adiposity [ 25 ]. A direct effect of SGLT2 inhibitors on alpha cells has also been proposed [ 26 , 27 ], though there are conflicting results [ 28 , 29 ] and further research is warranted.…”

Section: Clinical Efficacy Of Sglt2 Inhibitorsmentioning

confidence: 99%

SGLT2 Inhibitors: The Star in the Treatment of Type 2 Diabetes?

Saisho

2020

Diseases

View full text Add to dashboard Cite

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of oral hypoglycemic agents which increase urinary glucose excretion by suppressing glucose reabsorption at the proximal tubule in the kidney. SGLT2 inhibitors lower glycated hemoglobin (HbA1c) by 0.6–0.8% (6–8 mmol/mol) without increasing the risk of hypoglycemia and induce weight loss and improve various metabolic parameters including blood pressure, lipid profile and hyperuricemia. Recent cardiovascular (CV) outcome trials have shown the improvement of CV and renal outcomes by treatment with the SGLT2 inhibitors, empagliflozin, canagliflozin, and dapagliflozin. The mechanisms by which SGLT2 inhibitors improve CV outcome appear not to be glucose-lowering or anti-atherosclerotic effects, but rather hemodynamic effects through osmotic diuresis and natriuresis. Generally, SGLT2 inhibitors are well-tolerated, but their adverse effects include genitourinary tract infection and dehydration. Euglycemic diabetic ketoacidosis is a rare but severe adverse event for which patients under SGLT2 inhibitor treatment should be carefully monitored. The possibility of an increase in risk of lower-extremity amputation and bone fracture has also been reported with canagliflozin. Clinical trials and real-world data have suggested that SGLT2 inhibitors improve CV and renal outcomes and mortality in patients with type 2 diabetes (T2DM), especially in those with prior CV events, heart failure, or chronic kidney disease. Results of recent trials including individuals without diabetes may change the positioning of this drug as ″a drug for cardiorenal protection″. This review summarizes the potential of SGLT2 inhibitors and discusses their role in the treatment of T2DM.

show abstract

Section: Clinical Efficacy Of Sglt2 Inhibitorsmentioning

confidence: 99%

SGLT2 Inhibitors: The Star in the Treatment of Type 2 Diabetes?

Saisho

2020

Diseases

View full text Add to dashboard Cite

show abstract

“…Both amelioration of insulin resistance and daily glucose fluctuation are plausible pathophysiological mechanisms of reducing the risk of a cardiovascular event. Ectopic adiposities, especially as liver and muscle steatosis, can be the targets of SGLT2 inhibitor use in non-obese patients with T2DM (11,24). CCSs, with accumulating re-distributed ectopic fat from the adipose tissues to the liver and muscles, are good candidates to explain the pathophysiological mechanism of SGLT2 inhibitors, beyond its glucose-lowering effect.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Metreleptin and SGLT2 Inhibitor Combination Therapy Is Effective for Acquired Incomplete Lipodystrophy

et al. 2021

View full text Add to dashboard Cite

Childhood cancer survivors (CCSs) who have undergone bone marrow transplantation with systemic chemotherapy and whole-body irradiation often experience impaired glucose tolerance with marked insulin resistance. Incomplete acquired diabetic lipodystrophy should be considered as a late complication of bone marrow transplantation. A 24-year-old Japanese female patient with incomplete acquired lipodystrophy, a CCS of acute lymphocytic leukemia at the age of 3 years, was treated for diabetes mellitus and dyslipidemia at our hospital. Administration of multiple daily insulin injections (70 units/day), and oral administration of 500 mg/day metformin, 15 mg/day pioglitazone, and 200 mg/day bezafibrate had proven ineffective for her metabolic disorders. Subcutaneous administration of metreleptin improved her insulin resistance and hypertriglyceridemia within a month; however, it failed to maintain adequate plasma glucose levels in the long term. When oral administration of 10 mg/day empagliflozin was added to the metreleptin supplementation, her HbA1c value (National Glycohemoglobin Standardization Program) improved from 11% to 8%, which was maintained for an additional 18 months. This is the first case report of incomplete lipodystrophy that shows efficacy of a combination therapy with metreleptin and a sodium glucose cotransporter 2 (SGLT2) inhibitor for the treatment of diabetes and dyslipidemia. An SGLT2 inhibitor attenuates hyperglycemia through urinary glucose excretion and has been suggested to enhance lipid catabolism in the extra-adipose tissues, especially in the liver and skeletal muscles. Furthermore, metreleptin supplementation could enhance the action of the SGLT2 inhibitor by promoting satiety and lipolysis through the central nervous system. Combination therapy with metreleptin and an SGLT2 inhibitor was suggested to recover the volume of adipose tissue, possibly through improvement of insulin resistance in the adipose tissue. This report highlights the pathophysiological mechanism of an SGLT2 inhibitor in the improvement of glucose metabolism in non-healthy lean CCSs with insulin resistance. Administration of SGLT2 inhibitor, along with metreleptin supplementation, could be a good alternative therapy for diabetic lipodystrophy observed in CCSs.

show abstract

“…There were two other trials, i.e., AWARD-7 and LEADER, which have been completed. The AWARD-7 trial pertained to the study of dulaglutide in patients with type 2 diabetes and moderate to severe CKD (131). The LEADER trial dealt with the study of Liraglutide action in patients with diabetes with evaluation and cardiovascular outcome in CKD patients (132)…”

Section: Glucagon Like Peptide-1 Receptor Agonistmentioning

confidence: 99%

New Pandemic: Obesity and Associated Nephropathy

et al. 2021

View full text Add to dashboard Cite

Incidence of obesity related renal disorders have increased 10-folds in recent years. One of the consequences of obesity is an increased glomerular filtration rate (GFR) that leads to the enlargement of the renal glomerulus, i.e., glomerulomegaly. This heightened hyper-filtration in the setting of type 2 diabetes irreparably damages the kidney and leads to progression of end stage renal disease (ESRD). The patients suffering from type 2 diabetes have progressive proteinuria, and eventually one third of them develop chronic kidney disease (CKD) and ESRD. For ameliorating the progression of CKD, inhibitors of renin angiotensin aldosterone system (RAAS) seemed to be effective, but on a short-term basis only. Long term and stable treatment strategies like weight loss via restricted or hypo-caloric diet or bariatric surgery have yielded better promising results in terms of amelioration of proteinuria and maintenance of normal GFR. Body mass index (BMI) is considered as a traditional marker for the onset of obesity, but apparently, it is not a reliable indicator, and thus there is a need for more precise evaluation of regional fat distribution and amount of muscle mass. With respect to the pathogenesis, recent investigations have suggested perturbation in fatty acid and cholesterol metabolism as the critical mediators in ectopic renal lipid accumulation associated with inflammation, increased generation of ROS, RAAS activation and consequential tubulo-interstitial injury. This review summarizes the renewed approaches for the obesity assessment and evaluation of the pathogenesis of CKD, altered renal hemodynamics and potential therapeutic targets.

show abstract

Use of SGLT-2 Inhibitors in Patients with Type 2 Diabetes Mellitus and Abdominal Obesity: An Asian Perspective and Expert Recommendations

Cited by 38 publications

References 142 publications

SGLT2 Inhibitors: The Star in the Treatment of Type 2 Diabetes?

SGLT2 Inhibitors: The Star in the Treatment of Type 2 Diabetes?

Case Report: Metreleptin and SGLT2 Inhibitor Combination Therapy Is Effective for Acquired Incomplete Lipodystrophy

New Pandemic: Obesity and Associated Nephropathy

Contact Info

Product

Resources

About