Therapeutic Effect of Canagliflozin on Nephrotic Syndrome and Its Ultrasonic Evaluation / 中山大学学报(医学科学版)

ObjectiveTo investigate the therapeutic effect of antidiabetic drug canagliflozin （CGLZ） on adriamycin-induced nephrotic syndrome （NS） in rats， and the evaluation of contrast-enhanced ultrasound （CEUS） combined with color Doppler flow imaging （CDFI） during the treatment. MethodsA total of 56 male SD rats were randomly divided into normal group （NG）， model group （MG）， prednisone （PAT） group （PG）， low-dose single CGLZ group （LSCG）， high-dose single CGLZ group （HSCG）， low-dose CGLZ + PAT group （LUCG） and high-dose CGLZ + PAT group （HUCG）， with 8 rats in each group. The NS model in rats was induced by injecting adriamycin twice into the tail vein， and then the NS rats were treated by intragastric administration daily for 6 weeks with reference of PAT. Twenty-four hour urine total protein （24 h-UTP） was assessed one day before the start of oral administration and at the end of 2， 4 and 6 weeks after oral administration， respectively. CDFI and CEUS were performed on the right renal artery at the end of 6 weeks after oral administration， and the blood of abdominal aorta was taken for serological test the next day. ResultsCompared with those detection index of NG rats， the 24-hour UTP of MG rats increased （P＜0.01）， the serum ALB decreased and TG， TC， LDL increased （P＜0.01）， and CDFI shows that RRCT was thinner （P＜0.01） and the renal artery blood flow indicators RA-PI， RA-RI， RA-S/D all increased （P＜0.05）， and CEUS image shows that the TIC curve parameters TTP， AT， AUC all increased and DPI decrease in MG rats （P＜0.01）. After drug treatment， compared with those detection index of MG rats， 24 h-UTP decrease in LSCG after 2 weeks （P＜0.01）， and decrease significantly in all drug groups after 6 weeks （P＜0.01）； the serological test results show that the serum ALB in all CGLZ groups increased （P＜0.05）， TG decrease in LSCG （P＜0.01）， TC and LDL also decrease in LUCG after 6 weeks （P＜0.05）； CDFI shows that the RRCT thinning degree in all CGLZ is reduced （P＜0.01）， and the RA-PI in LSCG， RA-RI in PG， and RA-S/D in PG， LSCG， HSCG and LUCG rats all decreased （P＜0.05）； CEUS shows that the TTP， AT and AUC of renal TIC curve in drug treatment groups all decreased （P＜0.01）， and the DPI in PG， HSCG， LUCG and HUCG rats increased （P＜0.01）. ConclusionsCGLZ has the effect of treating NS， and the small dose is the best. CEUS combined with CDFI can be used to evaluate the renal morphology and hemodynamic changes of NS model rats before and after drug treatment， which is helpful to guide clinical application.

Research results and mechanism of sodium glucose cotransporter 2 inhibitors in the treatment of heart failure / 中国医师杂志

Sodium glucose cotransporter 2 inhibitor (SGLT2i) emerged as a new hypoglycemic agent, which can inhibit glucose reabsorption and thus play a hypoglycemic role. Recent studies have shown that SGLT2i not only lowers blood glucose, but also has a protective effect on the cardiovascular system, which may benefit patients with heart failure.The specific mechanism of action is still not fully elucidated. This paper aims to summarize the latest research results of SGLT2i in the treatment of heart failure, and analyze the possible mechanisms for clinical guidance.

Effect of sodium-glucose cotransporter 2 inhibitor on serum Chemerin, blood lipid level and insulin dosage in patients with type 2 diabetes and coronary heart disease / 中国医师杂志

Objective:To study the effect of sodium-glucose cotransporter 2 inhibitor (SGLT2i) on serum Chemerin, blood lipid levels and insulin dosage in patients with type 2 diabetes and coronary heart disease.Methods:The clinical data of 96 patients with type 2 diabetes mellitus and coronary heart disease admitted in Xianyang Central Hospital from June 2019 to June 2020 were retrospectively analyzed. According to different treatment methods, they were divided into control group and observation group, with 48 cases in each group. The control group was treated with insulin combined with metformin, and the observation group was treated with insulin combined with SGLT2i (this study mainly used dagglitazone). The blood glucose, serum Chemerin, blood lipid level and insulin dosage of the two groups were observed before and after treatment. The incidence of cardiovascular adverse events and adverse reactions were compared between the two groups.Results:After treatment, the levels of fasting blood glucose (FBG), 2 h PG (plasma glucose), glycosylated hemoglobin (HbA 1c), and Chemerin in the two groups were better than those before treatment ( P<0.05). The decrease in the levels of FBG, 2 h PG, HbA 1c and insulin dosage in the observation group were greater than those in the control group ( P<0.05). However, there was no difference in the decline of Chemerin levels between the two groups ( P>0.05). After treatment, the levels of total cholesterol (TC), triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) in the two groups were lower than before treatment, and the levels of high density lipoprotein cholesterol (HDL-C) were higher than before treatment (all P<0.05). The decrease of TG in the observation group was greater than that in the control group, the decrease of TC and LDL-C was samller than that in the control group, and the increase of HDL-C was greater than that in the control group (all P<0.05). The incidence of cardiovascular adverse events in the observation group was 4.17%(2/48), which was lower than that in the control group [16.67%(8/48), P<0.05]. Conclusions:SGLT2i has a significant therapeutic effect on patients with type 2 diabetes complicated with coronary heart disease. It can better control blood glucose and lipid levels and reduce insulin dosage, which is worthy of clinical application.

Progress of pharmacotherapy for heart failure / 中国临床药理学与治疗学

Heart failure is the terminal stage of all kinds of heart diseases. Despite the use of a variety of traditional drug standard treatment, the prognosis is still not ideal, and there is an urgent need for the update and improvement of new drugs and treatment methods. In recent years, angiotensin receptor-enkephalase inhibitors (Sacubitril/Valsartan), sodium-glucose cotransporter 2 inhibitors (SGLT-2i), soluble guanoside cyclase agonists (Vericiguat) and myocardial myosin activators omecamtiv mecarbil have been developed successively. SGLT2 inhibitors can improve ventricular load, reduce fibrosis and affect myocardial metabolism. sGC agonists play an anti-heart failure role by enhancing l-ARg-No-SGC-CGMP signaling pathway, improving myocardial and vascular function, reversing ventricular hypertrophy and fibrosis, slowing ventricular remodeling, and reducing ventricular afterload through systemic and pulmonary vasodilation. In addition, fineridone, a novel salt corticosteroid receptor antagonist, has also been reported in clinical studies in the field of heart failure. Therefore, it is the direction and hope for the development of heart failure in the future to select appropriate drugs for different types of patients with heart failure and carry out individualized treatment according to the optimized process of heart failure.

Dapagliflozin review : More than an anti-diabetic drug

@#Diabetes Mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action or both. DM is a significant health care concern. Worldwide, the prevalence is increasing at an alarming rate despite using different classes of anti-hyperglycemic agents. Although several treatment options reduce hyperglycemia, only half the patients achieve desirable glycemic targets. Newer treatments that significantly reduce hyperglycemia with novel mechanism of action and acceptable safety profiles are warranted to reduce complications associated with type 2 DM. Sodium-glucose cotransporter-2 inhibitors are anti-hyperglycemic agents with unique mechanism of action that lower blood glucose level independent of insulin. Recent findings on efficacy and safety establish their role in the treatment of DM. Sodium-glucose cotransporter-2 inhibitors may be an option in type 2 DM patients not willing or not ready to start insulin, those requiring additional glucose lowering and in those with acceptable risk factor profiles. Dapagliflozin (Farxiga) can be used at any stage of type 2 DM as a mono-therapy or in combination with other oral hypoglycemic agents and insulin. This review highlights the efficacy and safety of dapagliflozin as an anti-hyperglycemic agent and its use in co-morbid conditions like chronic kidney disease and cardiovascular diseases

Cetoacidosis diabética euglucémica asociada al uso de inhibidores del cotransportador de sodio-glucosa 2

RESUMEN Mujer de 48 años con antecedentes de diabetes mellitus tipo 2 tratada con empaglifozina acudió a consulta después de 8 horas de dolor abdominal, náuseas, vómitos y falta de aliento. Tras el examen físico, la paciente estaba alerta, álgica, pálida, con mucosas secas, taquipneica, taquicárdica y con dolor abdominal difuso sin signos de irritación peritoneal. Los resultados de su laboratorio mostraron una glucemia sérica de 115 mg/dL (70-100 mg/dL), gasometría arterial con acidosis metabólica con anión gap elevado 20 mmol/L. El análisis de orina reportó cetonuria (cuerpos cetónicos 150) y la HbA1C fue 12,4% (4,8%-6%). Se descartó una causa quirúrgica de dolor abdominal y finalmente fue diagnosticada con cetoacidosis diabética euglucémica secundaria al uso de Inhibidores del cotransportador de sodio-glucosa 2.

ABSTRACT A 48-year-old woman with a history of type 2 diabetes mellitus treated with empaglifozine came to consultation after 8 hours of abdominal pain, nausea, vomiting, and shortness of breath. After the physical examination, the patient was alert, allergic, pale, with dry mucosa, tachypnea, tachycardia, and with diffuse abdominal pain without signs of peritoneal irritation. The results of his laboratory showed a serum glucose of 115 mg/dL (70-100 mg/dL), arterial blood gasometry with metabolic acidosis with an elevated gap anion of 20 mmol/L. Urine analysis reported ketonuria (150 ketone bodies) and HbA1C was 12.4% (4.8% -6%). A surgical cause of abdominal pain was ruled out and she was finally diagnosed with euglycemic diabetic ketoacidosis secondary to the use of sodium-glucose cotransporter inhibitors 2.

Analysis of 2 cases of diabetic ketoacidosis / 中华内分泌代谢杂志

Diabetic ketoacidosis ( DKA ) is one of the common endocrine emergencies. With the development and applications of new drugs, the inducing causes of DKA become more and more complicated. We as clinicians should quickly and accurately evaluute the severity of DKA, and administrate reasonable rehydration and hypoglycemic treatment. What we should do better is searching the causes of DKA and help patients reasonably avoid its occurrence. In this article, two cases from clinical practice are analyzed.

A Review of the Effects of Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors on Lean Body Mass in Humans

Weight loss is an important goal in the management of several chronic conditions, including type 2 diabetes mellitus, and pharmacological therapies that aid weight loss are appealing. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) are novel glucose-lowering therapies that have been shown to induce clinically significant reductions in body weight. However, this weight loss may not be attributed solely to fat mass (FM). Given the importance of skeletal muscle and lean body mass (LBM) on cardio-metabolic health and physical function, we reviewed the available literature reporting the effects of GLP-1RAs and SGLT2is on body composition. Results demonstrate that, in most circumstances, the weight loss associated with both therapies predominantly comprises a reduction in FM, although significant heterogeneity exists between studies. In over half of the studies identified, the proportion of LBM reduction ranged between 20% and 50% of total weight lost, which is consistent with diet-induced weight loss and bariatric surgery. No clear differences existed between GLP-1RAs and SGLT2is. Consequently, the loss of LBM and skeletal muscle associated with weight loss induced by GLP-1RAs and SGLT2is warrants attention. Strategies to preserve skeletal muscle and improve physical function, for example through structured exercise, are of great importance.

Sodium-Glucose Cotransporter 2 Inhibitors for People with Type 1 Diabetes / 임상당뇨병

Althowgh intensive insulin regimen is the main treatment in people with type 1 diabetes, glucose variability and weight gain remain as challenges for this treatment. Sodium-glucose cotransporter (SGLT) inhibitors (including the SGLT1/2 inhibitors) have emerged as an add-on therapy for insulin treatment in peoples with type 1 diabetes due to their insulin-independent mechanism. Recent clinical trials have consistently reported that SGLT inhibition provides additive benefits in glycemic control, including lower insulin dose and weight loss. However, there is concern that an increase in ketone-related adverse events such as diabetic ketoacidosis is higher in SGLT1/2, as well as SGLT2 inhibitors. Despite safety issues that require further evaluation, SGLT2 inhibitors used with caution may provide an adjunctive therapy in people with type 1 diabetes.

Advance in the mechanism of protective effects of SGLT2 inhibitor on diabetic kidney disease / 复旦学报（医学版）

Diabetic kidney disease DKD) is one of the major causes for end-stage renal disease (ESRD),which has been the focus of both clinical and basic research.Sodium-glucose cotransport 2 (SGLT2) inhibitors are a new type of anti-diabetic drugs,which also showed reno-proteetive effects.The potential mechanisms include decreasing plasma glucose,improving glomerular hyperfiltration,reducing oxidative stress,alleviating tubulointerstitial injury,suppressing inflammation and fibrosis,decreasing the level of uric acid,and etc.This review focuses on the advance in the mechanism of protective effects of SGLT2 inhibitor on DKD.

Meta-analysis of SGLT2 inhibitors and stroke risk in type 2 diabetic patients / 中华内分泌代谢杂志

Objective To evaluate the effects of sodium-glucose cotransporter 2 ( SGLT2) inhibitors on the stroke risk for patients with type 2 diabetes mellitus (T2DM). Methods A systemic meta-analysis including 30 random control trails ( RCTs) was performed to compare the risk of stroke between type 2 diabetic patients treated with SGLT2 inhibitors and control drugs. Then their bias risk and quality were assessed and meta-analysis was conducted using Stata12.0 software. Results Thirty RCTs enrolling 74456 participants were selected for meta-analysis. The stroke incidence in the group receiving SGLT2 inhibitor monotherapy or combination therapy did not significantly differ from that in control group, with relative risk (RR) 1.01 (95％CI 0.93-1.10, P=0.978) and 1.00 (95％CI 0.92-1.09, P=0. 874 ) , respectively. Three SGLT2 inhibitors canagliflozin, dapagliflozin, and empagliflozin did not increase the risk of stroke, with similar RR values ( RR=0.91, 0.99, 1.13, respectively) . Subgroup analyses showed that there was no correlation between SGLT2 inhibitors and stroke risk in different gender, age, diabetes duration, body mass index, or HbA1C levels. Conclusions Whether administered as monotherapy or add-on therapy, SGLT2 inhibitors did not increase stroke incidence, and there were no significant within-class differences.

Effect of Dapagliflozin on Alanine Aminotransferase Improvement in Type 2 Diabetes Mellitus with Non-alcoholic Fatty Liver Disease

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are expected to improve the liver function of patients with non-alcoholic fatty liver disease (NAFLD) combined type 2 diabetes mellitus (T2DM) by its characteristic mechanism. This study was designed to investigate the effect of dapagliflozin, one of the SGLT2i, on the liver function of T2DM with NAFLD when combined with metformin. METHODS: Among patients who received dual oral hypoglycemic agents within the 3 months of diagnosing NAFLD, patients who had abnormal alanine aminotransferase (ALT) level (>40 IU/L) were included. Patients were divided into two groups: metformin+dapagliflozin group and metformin+dipeptidyl peptidase-4 inhibitors (DPP4i) group. Demographic data, biochemical data and the clinical and treatment histories of all patients were reviewed. RESULTS: A total of 102 patients were included (dapagliflozin group, n=50; DPP4i group, n=52). Dapagliflozin group showed more weight loss and more ALT decline than DPP4i group (−2.9 kg vs. −0.4 kg, P=0.005; −21.1 U/L vs. −9.5 U/L, P=0.008, respectively) and the proportion of patients with ALT normalization after treatment was also significantly higher in the dapagliflozin group (80.0% vs. 61.5%, P=0.041). The effect of dapagliflozin with metformin on ALT normalization remained significant after adjustment for confounding variables including body weight loss (odds ratio, 3.489; P=0.046). CONCLUSION: ALT improvement was statistically significant in the dapagliflozin than the DPP4i when combined with metformin and the result was consistent after adjustment for confounding variables including body weight loss.

Preventive Effect of an SGLT2 Inhibitor on Cardiovascular Disease in an Observational Study: Results from a Korean Population / 임상당뇨병

The sodium-glucose cotransporter-2 inhibitor (SGLT2i) is a new anti-hyperglycemic agent that have function to concomitantly inhibit the reabsorption of glucose and sodium in the renal proximal convoluting tubule. Recent two cardiovascular outcome trials showed that a lower risk of cardiovascular events with SGLT2i in people with type 2 diabetes. In addition, prior real-world data demonstrated similar SGLT2i effects, but these studies were limited to the United States and Europe. Thus, the CVD-REAL (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors) 2 Study was investigated cardiovascular outcomes in those initiated on SGLT2i versus other glucose-lowering drugs (oGLDs) across 6 countries in the Asia Pacific, the Middle East, and North American regions. In Korea, 336,644 episodes of initiation in SGLT2i or oGLD group between September 2014 and December 2016 were identified in Korea National Health Insurance database after propensity score matching. SGLT2i users was associated with a lower risk of all-cause death (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.67~0.77), hospitalization for heart failure (HHF) (HR, 0.87; 95% CI, 0.82~0.92), all-cause death or HHF (HR, 0.81; 95% CI, 0.78~0.85), myocardial infarction (HR, 0.81; 95% CI, 0.74~0.89), and stroke (HR, 0.82; 95% CI, 0.78~0.86) compared with oGLD users. In conclusion, initiation of SGLT2i had a lower risk of cardiovascular events in people with type 2 diabetes compared with oGLDs.

Development of a method to study the activity and selectivity of SGLT2 inhibitors / 药学学报

The purpose of this study was to develop a screening method to determine the activity and selectivity of SGLT2 inhibitor. Human SGLT1/SGLT2 cDNA was inserted into the pMSCVpuro mammalian expression vector and the plasmid was transfected into HEK293 cells. Stably transfected clones were selected in puromycin containing medium. To evaluate the expression of human SGLT1 and SGLT2 in stable transfected cells, RT-PCR, Western blot and immunofluorescence analysis were performed. 1-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-1-deoxy-D-glucose (1-NBDG) was used as a substrate in the uptake assay to evaluate the Na+ dependent glucose transport activities of SGLT1/2. The inhibitory activity and selectivity of dapagliflozin/phloridzin were also determined, respectively. The hypoglycemic efficacy of dapagliflozin was evaluated in mice with normal blood glucose and mice with alloxan-induced T1DM. The result showed that SGLT1 was overexpressed in pMSCVpuro-SGLT1 transfected HEK293 cells. SGLT2 protein was overexpressed in pMSCVpuro-SGLT2 transfected HEK293 cells and located in both cytoplasm and membrane. The Na+ dependent 1-NBDG uptake was significantly increased in pMSCVpuro-SGLT1/SGLT2 transfected cells compared to that in pMSCVpuro-null transfected cells. The selectivity of dapagliflozin, whose half maximal inhibitory concentration (IC50) for SGLT2 (2.24×10-10 mol·L-1) was far lower than that for SGLT1 (6.20×10-7 mol·L-1), was better than that of phloridzin. The oral glucose tolerance was elevated after a single dose of dapagliflozin in normal mice. In T1DM mice, compared with model group, no-fasting glucose level was decreased at 1 h after administration and maintained at a lower level for 24 h in a dose-dependent manner. A 20-day administration with dapagliflozin dose-dependently improved the hyperglycemia status. Taken together, a system to evaluate the activity and selectivity of SGLT2 inhibitors was established using 1-NBDG in vitro and the hypoglycemic efficacy in vivo in this study. The advantages of this system include non-radioactivity, high efficiency, and good stability which may provide a technique platform for development of novel SGLT2 inhibitors.

Potential benefit of the combination therapy of dipeptidyl peptidase-4 inhibitor with sodium-glucose cotransporter-2 inhibitor in patients with type 2 diabetes mellitus: From the standpoint of renoprotection / 中华内分泌代谢杂志

Both dipeptidyl peptidase-4(DPP-4)inhibitor and sodium-glucose cotransporter-2(SGLT-2) inhibitor have been approved for the treatment of type 2 diabetes mellitus(T2DM). In preclinical or clinical studies, DPP-4 inhibitor shows a potential beneficial effect on renal architecture damage,whereas SGLT-2 inhibitor has a role in renoprotection by improving renal hemodynamics. Therefore,the combination therapies with DPP-4 inhibitor and SGLT-2 inhibitor not only improve metabolic control, but also may have a synergistic or complementary effect in protecting renal structure and function in patients with T2DM. This combination therapy provides a novel option for raising the comprehensive management level in patients with T2DM.

Addition of Ipragliflozin to Metformin Treatment in Korean Patients with Type 2 Diabetes Mellitus: Subgroup Analysis of a Phase 3 Trial

BACKGROUND: This is a subgroup analysis of Korean patients from a phase 3 clinical trial investigating the efficacy and safety of ipragliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin. METHODS: This multicenter, placebo-controlled, double-blind, parallel-group study was carried out between November 2011 and January 2013. Patients entered a 2-week placebo pretreatment period, followed by a 24-week treatment period with either ipragliflozin (50 mg/day) or placebo, while continuing metformin. Efficacy outcomes (glycosylated hemoglobin [HbA1c], fasting plasma glucose [FPG], and body weight) and safety outcomes (treatment-emergent adverse events [TEAEs]) were measured and compared between the two treatment groups for patients enrolled in all 18 study sites in Korea. RESULTS: Eighty-two Korean patients received ipragliflozin (n=43) or placebo (n=39) during the study period. Mean changes in HbA1c levels from baseline to the end of treatment were –0.97% in the ipragliflozin group and –0.31% in the placebo group, with an adjusted between-group difference of –0.60% (P<0.001). Compared to placebo, FPG and body weight also decreased significantly (both P<0.001) from baseline after treatment in the ipragliflozin group, with between-group differences of –21.4 mg/dL and –1.53 kg, respectively. Decreased weight was the most common TEAE in the ipragliflozin group (7.0%); there were no reports of genital and urinary tract infection. CONCLUSION: Ipragliflozin treatment in addition to metformin led to significant improvement in glycemic outcomes and reduction in body weight in Korean patients with type 2 diabetes mellitus, compared with metformin treatment alone; the safety profile was comparable in both groups.

New anti-diabetic agents

Diabetes mellitus is characterized by hyperglycemia due to insulin deficiency and/or insulin resistance. Cardiovascular disease (CVD) is a major comorbidity of type 2 diabetes mellitus, and is the most common cause of death in people with diabetes mellitus. Several clinical trials have addressed the long-term effects of near-normoglycemia on CVD, but did not find evidence of an effect. However, some recent clinical trials of sodium glucose cotransporter 2 inhibitors (EMPA-REG [Empagliflozin Cardiovascular Outcomes and Mortality in Type 2 Diabetes Trial], CANVAS [Canagliflozin Cardiovascular Assessment Study]) or glucagon-like peptide-1 agonists (LEADER [Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results-A Long Term Evaluation], SUSTAIN-6 [Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes]) showed very promising results regarding the prevention of CVD. In this review, I discuss some of these new anti-diabetic agents and present clinical information regarding these drugs.

Emerging Safety Issues of Dipeptidyl Peptidase-4 Inhibitors and Sodium Glucose Cotransporter 2 Inhibitors: How to Interpret and Apply in Clinical Practice / 임상당뇨병

Dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium glucose co-transporter 2 (SGLT2) inhibitors are newer classes of glucose-lowering agents that are currently widely used in clinical practice. Their glycemic efficacy and cardiovascular safety have been well proven, and recent large clinical trials even have shown cardiovascular benefits of SGLT2 inhibitors. However, data regarding drug-related long-term safety remain inconclusive. Recently, several safety issues related to DPP-4 inhibitors and SGLT2 inhibitors have been raised by cardiovascular outcome trials or post-marketing pharmacoepidemiological studies. In this review, we summarize emerging safety issues regarding the use of DPP-4 inhibitors and SGLT2 inhibitors in type 2 diabetes and suggest how to interpret and apply these results to clinical practice.

Euglycemic Diabetic Ketoacidosis When Reducing Insulin Dosage in Patients Taking Sodium Glucose Cotransporter 2 Inhibitor / 이화의대지

Sodium glucose cotransporter 2 (SGLT2) inhibitor has been recently reported of diabetic ketoacidosis due to accumulation of ketone bodies in patients with severe dehydration caused from such like diarrhea even though the patient had normal glucose level. This is a case of ketoacidosis in normal glucose level as production of ketone bodies is stimulated in liver with increased secretion of glucagon by stimulation of α cells in pancreas due to increase of lipolysis caused from reducing insulin and by SGLT2 inhibitor among patients who are under concurrent insulin and SGLT2 inhibitor. Thus, insulin dosage reduction requires caution in order to control blood glucose level on combined treatment of SGLT2 inhibitor in a patient who is administering insulin because the patient may be caused ketoacidosis in normal blood glucose level.

Dapagliflozin's Effects on Glycemia and Cardiovascular Risk Factors and Incidence of Adverse Events in Patients with Type 2 Diabetes

BACKGROUND: Dapagliflozin is an oral selective inhibitor of sodium-glucose cotransporter 2(SGLT2), the kidney transporter chiefly responsible for glucose reabsorption from the glomerular filtrate. Because this mechanism does not require the action of insulin, dapagliflozin rarely causes hypoglycemia. Dapagliflozin may affect blood glucose control as well as blood pressure and the body weight which are one of the cardiovascular disease risk factors. However, dehydration and ketoacidosis are reported as the side effects of the dapagliflozin treatment and the safety issues have been occurred. The aim of this study is to analyze the effectiveness and adverse events of dapagliflozin in Korean patients. METHODS: From December 2014 to August 2015, we retrospectively reviewed the electronic medical records of type 2 diabetes patients who were prescribed dapagliflozin at Severance Hospital. RESULTS: A total of 202 Korean patients were enrolled in this study. The effectiveness in the reduction of blood glucose was statistically significant(p < 0.001). Dapagliflozin decreased 0.74% of HbA1c after 24 weeks. Significantly more participants achieved the target HbA1c level(HbA1c < 7%) after 24 weeks(n=42, 35.3%) than before taking dapagliflozin(n=21, 17.6%). Blood pressure decreased 5.7 mmHg s ystolic b lood p ressure(SBP), 1.9 mmHg d iastolic b lood p ressure(DBP) a fter 24 weeks. M ore than o ne q uarter of participants(n=35, 29.4%) experienced weight loss. Most common adverse event was genitourinary symptoms. CONCLUSION: In this study, the effectiveness of dapagliflozin in improving glycemic control, blood pressure control, and weight loss was statistically significant. However, elderly and female patients, who have higher incidence of adverse events, should use dapagliflozin cautiously.