Sodium-glucose co-transporter-2 inhibitor use and dietary carbohydrate intake in Japanese individuals with type 2 diabetes: A randomized, open-label, 3-arm parallel comparative, exploratory study.

Published on May 1, 2017in Diabetes, Obesity and Metabolism5.9
· DOI :10.1111/DOM.12848
Daisuke Yabe35
Estimated H-index: 35
Masahiro Iwasaki11
Estimated H-index: 11
+ 7 AuthorsYutaka Seino87
Estimated H-index: 87
This study investigated the safety and efficacy of the sodium-glucose co-transporter-2 (SGLT2) inhibitor luseogliflozin with differing carbohydrate intakes in Japanese individuals with type 2 diabetes (T2D). Participants were randomly assigned to 3 carbohydrate-adjusted meals for 14 days (days 1-14; a high carbohydrate [HC; 55% total energy carbohydrate] and high glycaemic index [HGI] meal; an HC [55% total energy carbohydrate] and low glycaemic index [LGI] meal; or a low carbohydrate [LC; 40% total energy carbohydrate] and HGI meal). All participants received luseogliflozin for the last 7 days (days 8-14), continuous glucose monitoring (CGM) before and after luseogliflozin treatment (days 5-8 and days 12-15) and blood tests on days 1, 8 and 15. Luseogliflozin significantly decreased the area under the curve and mean of CGM values in all 3 groups similarly. Fasting plasma glucose, insulin and glucagon were similar at all time points. Ketone bodies on day 15 were significantly higher in the LC-HGI group compared with the HC-HGI and HC-LGI groups. In conclusion, luseogliflozin has similar efficacy and safety in Japanese people with T2D when meals contain 40% to 55% total energy carbohydrate, but a strict LC diet on this class of drug should be avoided to prevent SGLT2 inhibitor-associated diabetic ketoacidosis.
📖 Papers frequently viewed together
33 Citations
5,575 Citations
9 Authors (Ele Ferrannini, ..., Elza Muscelli)
284 Citations
#1Wataru Ogawa (Kobe University)H-Index: 61
#2Kazuhiko Sakaguchi (Kobe University)H-Index: 21
Diabetic ketoacidosis (DKA) is a serious acute complication of diabetes mellitus that occasionally can become life threatening. It is induced as a result of a profound deficiency of insulin action in the body, often developing in individuals with poorly controlled type 1 diabetes or in those with type 2 diabetes who are subject to external stress such as infection, injury, or surgery. Although DKA is typically associated with marked hyperglycemia and resultant dehydration, it can occur with only...
163 CitationsSource
Recently, the U.S. Food and Drug Administration (FDA) issued a Drug Safety Communication that warns of an increased risk of diabetic ketoacidosis (DKA) with uncharacteristically mild to moderate glucose elevations (euglycemic DKA [euDKA]) associated with the use of all the approved sodium–glucose cotransporter 2 (SGLT2) inhibitors (1). This Communication was based on 20 clinical cases requiring hospitalization captured between March 2013 and June 2014 in the FDA Adverse Event Reporting System da...
392 CitationsSource
#1Rimei Nishimura (Jikei University School of Medicine)H-Index: 19
#2T. OsonoiH-Index: 1
Last. Yoshishige Samukawa (Taisho Pharmaceutical Co.)H-Index: 12
view all 9 authors...
The aim of the present study was to determine the effects of luseogliflozin on 24-h glucose levels, assessed by continuous glucose monitoring, and on pharmacodynamic variables measured throughout the day. In this double-blind, placebo-controlled, crossover study, 37 patients with type 2 diabetes mellitus inadequately controlled with diet and exercise were randomized into two groups. Patients in each group first received luseogliflozin then placebo for 7 days each, or vice versa. After 7 days of ...
34 CitationsSource
#1Naoko Tajima (Jikei University School of Medicine)H-Index: 62
#2Mitsuhiko NodaH-Index: 62
Last. Masakazu Haneda (Asahikawa Medical University)H-Index: 31
view all 10 authors...
79 CitationsSource
#1Simeon I. Taylor (UMB: University of Maryland, Baltimore)H-Index: 77
#2Jenny E. Blau (NIH: National Institutes of Health)H-Index: 11
Last. Kristina I. Rother (NIH: National Institutes of Health)H-Index: 45
view all 3 authors...
Context: Sodium glucose cotransporter 2 (SGLT2) inhibitors are antidiabetic drugs that increase urinary excretion of glucose, thereby improving glycemic control and promoting weight loss. Since approval of the first-in-class drug in 2013, data have emerged suggesting that these drugs increase the risk of diabetic ketoacidosis. In May 2015, the Food and Drug Administration issued a warning that SGLT2 inhibitors may lead to ketoacidosis. Evidence Acquisition: Using PubMed and Google, we conducted ...
306 CitationsSource
#1Daisuke Yabe (Kobe University)H-Index: 35
#2Rie NishikinoH-Index: 2
Last. Yutaka Seino (KEPCO: Korea Electric Power Corporation)H-Index: 9
view all 5 authors...
Sodium/glucose co-transporter 2 inhibitors (SGLT2i) represent a novel class of glucose-lowering agents that lower plasma glucose levels through pharmacological inhibition of glucose reuptake from the kidney, independent of insulin secretion and action. Clinical trials of SGLT2i demonstrated therapeutic benefits on glycemic control and bodyweight in individuals with type 2 diabetes, with few cases of serious adverse events (SAEs). However, a considerable number of SAEs were reported in patients r...
57 CitationsSource
#1Takashi Sasaki (Jikei University School of Medicine)H-Index: 16
#2Yutaka SeinoH-Index: 87
Last. Yoshishige Samukawa (Taisho Pharmaceutical Co.)H-Index: 12
view all 6 authors...
Introduction Luseogliflozin, a potent, selective sodium glucose cotransporter 2 inhibitor, promotes urinary glucose excretion (UGE) and reduces plasma glucose concentrations. Luseogliflozin was approved for use in Japan after favorable pharmacokinetic, pharmacodynamic, and safety profiles were reported in healthy Japanese subjects and patients with type 2 diabetes mellitus (T2DM) in clinical development studies. We aimed to investigate the pharmacokinetics, pharmacodynamics, and safety of multip...
14 CitationsSource
#1Tomohide Hayami (Aichi Medical University)H-Index: 2
#2Yoshiro Kato (Aichi Medical University)H-Index: 13
Last. Jiro Nakamura (Aichi Medical University)H-Index: 41
view all 19 authors...
We present a case of a 32-year-old diabetic woman with Prader–Willi syndrome who developed severe ketoacidosis caused by a sodium-glucose cotransporter 2 (SGLT2) inhibitor, a novel class of antihyperglycemic agents, during a strict low-carbohydrate diet. At admission, a serum glucose level of 191 mg/dL was relatively low, though laboratory evaluations showed severe ketoacidosis. This is the first report of ketoacidosis caused by a SGLT2 inhibitor. It is necessary to not only pay attention when u...
83 CitationsSource
#1Farhad M. Hasan (UVA: University of Virginia)H-Index: 1
#2Mazen Alsahli (U of T: University of Toronto)H-Index: 4
Last. John E. Gerich (UR: University of Rochester)H-Index: 76
view all 3 authors...
Abstract The kidney plays an important role in glucose homeostasis via its production, utilization, and, most importantly, reabsorption of glucose from glomerular filtrate which is largely mediated via the sodium glucose co-transporter 2 (SGLT2). Pharmacological inhibition of SGLT2 increases urinary glucose excretion and decreases plasma glucose levels in an insulin-independent manner. Agents that inhibit SGLT2 represent a novel class of drugs, which has recently become available for treatment o...
97 CitationsSource
#1Yoshihito Fujita (Kyoto University)H-Index: 14
#2Nobuya Inagaki (Kyoto University)H-Index: 82
Type 2 diabetes is characterized by impaired insulin secretion from pancreatic β-cells and/or reduced response of target tissues to insulin. Good glycemic control delays the development and slows the progression of micro- and macrovascular complications. Although there are numerous glucose-lowering agents in clinical use, only approximately half of type 2 diabetic patients achieve glycemic control, and undesirable side-effects often hamper treatment in those treated with the medications. There i...
105 CitationsSource
Cited By42
#1Nitin Kapoor (Christian Medical College & Hospital)H-Index: 9
#2Rakesh SahayH-Index: 24
Last. Ashok Kumar Das (JIPMER: Jawaharlal Institute of Postgraduate Medical Education and Research)H-Index: 20
view all 17 authors...
Diabetes and obesity are both increasing at a fast pace and giving rise to a new epidemic called diabesity. Lifestyle interventions including diet play a major role in the treatment of diabetes, obesity and diabesity. There are many guidelines on dietary management of diabetes or obesity globally and also from South Asia. However, there are no global or South Asian guidelines on the non-pharmacological management of diabesity. South Asia differs from the rest of the world as South Asians have di...
#1Xiaodan Wang (Tianjin University of Traditional Chinese Medicine)
#2Jingyu Ni (Tianjin University of Traditional Chinese Medicine)H-Index: 7
Last. Guanwei Fan (Tianjin University of Traditional Chinese Medicine)H-Index: 23
view all 7 authors...
Heart failure (HF) often coexists with insulin resistance (IR), and the incidence of HF in type 2 diabetes mellitus (T2DM) patients is significantly higher. The reciprocal relationship between HF and IR has long been recognized, and the integration complicates the therapy of both. A number of mechanisms ascribe to the progression of cardiac IR, in which the main factors are the shift of myocardial substrate metabolism. Studies have found that SGLT2 inhibitors, an anti-diabetic drug, can improve ...
1 CitationsSource
#1Mark Cucuzzella (WVU: West Virginia University)H-Index: 2
Last. Diana Isaacs (Cleveland Clinic)H-Index: 7
view all 3 authors...
Healthcare professionals need to be competent to safely adapt diabetes medications when patients with Type 2 Diabetes (T2D) alter their diet. Safe prescribing is supported through an understanding of the clinical evidence, basic science, and pharmacology of medications. This review article supports clinicians in the practical application of this knowledge to achieve safe practice. Traditional medical training and clinical practice for chronic disease has revolved around the teaching of intensify...
#1Preethika Ekanayake (UCSD: University of California, San Diego)H-Index: 1
#2Christopher J. Hupfeld (UCSD: University of California, San Diego)H-Index: 10
Last. Sunder Mudaliar (UCSD: University of California, San Diego)H-Index: 65
view all 3 authors...
PURPOSE OF REVIEW The micro/macrovascular complications of diabetes cause considerable morbidity and premature mortality. The SGLT2 inhibitors are the first diabetes medications with significant benefits on microvascular disease (nephropathy) and macrovascular cardiovascular disease. In this review, we evaluate one of the potential mechanisms for these cardiorenal benefits-the production of ketones, their benefits, and risks. RECENT FINDINGS In recent cardiovascular outcome trials (CVOTs), the S...
3 CitationsSource
#1Yoshiaki TamuraH-Index: 27
#2Takuya OmuraH-Index: 5
Last. Atsushi ArakiH-Index: 24
view all 4 authors...
The increasing prevalence of older adults with diabetes has become a major social burden. Diabetes, frailty, and cognitive dysfunction are closely related to the mechanisms of aging. Insulin resistance, arteriosclerosis, chronic inflammation, oxidative stress, and mitochondrial dysfunction may be common mechanisms shared by frailty and cognitive impairment. Hyperglycemia, hypoglycemia, obesity, vascular factors, physical inactivity, and malnutrition are important risk factors for cognitive impai...
8 CitationsSource
Introduction Treatment using sodium-glucose cotransporter (SGLT) 2 inhibitor and low-carbohydrate diet (LCD) for obesity and type 2 diabetes are similar in terms of carbohydrate limitation. However, their mechanisms of action differ, and the effects on the body remain unclear. We investigated the effects of SGLT2 inhibitor and LCD on body composition and metabolic profile using the db/db mouse model for obesity and type 2 diabetes. Research design and methods Eight-week-old male db/db mice were ...
4 CitationsSource
#1Samantha Steinmetz-Wood (UVM: University of Vermont)H-Index: 1
#2Matthew P. Gilbert (UVM: University of Vermont)H-Index: 9
Last. Katherine Menson (UVM: University of Vermont)H-Index: 2
view all 3 authors...
Results from major clinical trials have shown significant cardiorenal-protective benefits of SGLT2 inhibitors in patients with type 2 diabetes (T2DM), leading to increased popularity. A rare but serious side effect of SGLT2 inhibitors is euglycemic diabetic ketoacidosis (EDKA), which presents more covertly but has been described. Identification and report of modifiable risk factors would be an important step in helping clinicians appropriately counsel patients. In this case report, we present DK...
5 CitationsSource
#1Nicola FlemingH-Index: 3
#2P. S. Hamblin (University of Melbourne)H-Index: 11
Last. Elif I EkinciH-Index: 25
view all 4 authors...
INTRO: Sodium glucose cotransporter 2 inhibitors (SGLT2i) have emerged as an important class of blood glucose lowering medications due to cardiovascular, metabolic and renal benefits. However, there is a small but significant risk of diabetic ketoacidosis (DKA) associated with their use. METHODS: A literature search was conducted in Ovid MEDLINE and Embase to July 2019 using variants on the key search terms sodium-glucose cotransporter 2, diabetic ketoacidosis and type 2 diabetes. A broad spectr...
9 CitationsSource
#1Erasmia Sampani (A.U.Th.: Aristotle University of Thessaloniki)H-Index: 3
#2Pantelis A. Sarafidis (A.U.Th.: Aristotle University of Thessaloniki)H-Index: 48
Last. Aikaterini Papagianni (A.U.Th.: Aristotle University of Thessaloniki)H-Index: 21
view all 3 authors...
Sodium-glucose co-transporters 2 (SGLT-2) inhibitors are a relatively novel class of oral medications for the treatment of Type 2 Diabetes Mellitus, which lower plasma glucose by inhibiting glucose...
4 CitationsSource