Mid-term quality of life after gastric band removal and single-stage conversion to gastric bypass: a single-center cohort study.

BACKGROUND: Revision surgeries in patients with failed gastric banding including band removal are increasingly necessary. However, long-term outcomes after band removal alone are unsatisfactory due to weight regain and limited improvement in quality of life. This study aimed to report mid-term quality of life outcomes after gastric band removal and single-stage conversion to Roux-en-Y gastric bypass. METHODS: Data of 108 patients who underwent conversion surgery from 2011 to 2017 were extracted from a prospective database and retrospectively analyzed. During follow-up visits, physical and laboratory data as well as quality of life questionnaires were obtained. RESULTS: Postoperative mean Moorehead score increased significantly after 1 year (1.62 ± 0.86, p < 0.001) and after 5 years (1.55 ± 0.84, p < 0.001) compared to baseline values (0.72 ± 1.1). The mean follow-up time was 53 months. Moorehead scores at 1, 2, and 5 years postoperative were available in 75% (n = 81), 71% (n = 77), and 42% (n = 45) of cases, respectively. Mixed ANOVA analysis showed a significantly superior increase in Moorehead score in males (p = 0.024). No other significant predictors were identified. Lasting BMI reduction (- 4.6 to 33.0 ± 6.7 kg/m2, p < 0.001) and weight loss (- 12.9% (- 13.6 kg), p < 0.001) 5 years after conversion surgery were seen. Postoperative complications occurred in 35% (n = 38) of patients with a re-operation rate of 30.5% (n = 33). CONCLUSION: The current study shows that band removal with single-stage gastric bypass in patients with failed gastric banding leads to a lasting improvement in quality of life and may be the rescue procedure of choice in this setting.

Intralabyrinthine schwannomas : Surgical management and hearing rehabilitation with cochlear implants.

Intralabyrinthine schwannomas (ILS) are a rare differential diagnosis of sudden hearing loss and vertigo. In an own case series of 12 patients, 6 tumors showed an intracochlear, 3 an intravestibular, 1 a transmodiolar including the cerebellopontine angle (CPA), 1a transotic including the CPA, and 1 a multilocular location. The tumors were removed surgically in 9 patients, whereas 3 patients decided for a "wait-and-test-and-scan" strategy. Of the surgical patients, 3 underwent labyrinthectomy and cochlear implant (CI) surgery in a single-stage procedure; 1 patient had extended cochleostomy with CI surgery; 3 underwent partial or subtotal cochleoectomy, with partial cochlear reconstruction and CI surgery (n = 1) or implantation of electrode dummies for possible later CI after repeated MRI follow-up (n = 2); and in 2 patients, the tumors of the internal auditory canal and cerebellopontine angle exhibiting transmodiolar or transmacular growth were removed by combined translabyrinthine-transotic resection. For the intracochlear tumors, vestibular function could mostly be preserved after surgery. In all cases with CI surgery, hearing rehabilitation was successful, although speech discrimination was limited for the case with subtotal cochleoectomy. Surgical removal of intracochlear schwannomas via partial or subtotal cochleoectomy is, in principle, possible with preservation of vestibular function. In the authors' opinion, radiotherapy of ILS is only indicated in isolated cases. Cochlear implantation during or after tumor resection (i. e., as synchronous or staged surgeries) is an option for hearing rehabilitation in cartain cases and represents a therapeutic approach in contrast to a "wait-and-test-and-scan" strategy.

[Intralabyrinthine schwannomas : Surgical management and hearing rehabilitation with cochlear implants. German version]. / Intralabyrinthäre Schwannome : Chirurgisches Management und Hörrehabilitation mit Cochleaimplantaten.

Intralabyrinthine schwannomas (ILS) are a rare differential diagnosis of sudden hearing loss and vertigo. In an own case series of 12 patients, 6 tumors showed an intracochlear, 3 an intravestibular, 1 a transmodiolar including the cerebello-pontine angle (CPA), 1 a transotic including the CPA and 1 a multilocular location. The tumors were removed surgically in 9 patients, whereas 3 patients opted for a "wait-and-test-and-scan" strategy. Of the surgical patients, 3 underwent labyrinthectomy and cochlear implant (CI) surgery in a single stage procedure; 1 patient received extended cochleostomy with CI surgery; 3 underwent partial or subtotal cochleoectomy, with partial cochlear reconstruction and CI surgery (n = 1) or implantation of electrode dummies for possible later CI following repeated MRI follow-up (n = 2); and in 2 patients, the tumors of the internal auditory canal and cerebellopontile angle exhibiting transmodiolar or transmacular growth were removed by combined translabyrinthine-transotic resection. For the intracochlear tumors, vestibular function could mostly be preserved after surgery. In all cases with CI surgery, hearing rehabilitation was successful, although speech discrimination was limited for the case with subtotal cochleoectomy. Surgical removal of intracochlear schwannomas via partial or subtotal cochleoectomy is, in principle, possible with preservation of vestibular function. In the authors' opinion, radiotherapy of ILS is only indicated in isolated cases. Provided performed early enough, cochlear implantation after surgical removal of ILS is an option for auditory rehabilitation, thus representing-in contrast to the "wait-and-test-and-scan" strategy-a therapeutic approach.

Model-based exposure-response analysis of apixaban to quantify bleeding risk in special populations of subjects undergoing orthopedic surgery.

Population pharmacokinetic (PK) and exposure-response analyses of apixaban were performed using data from phase I-III studies to predict bleeding risks for patients receiving apixaban 2.5 mg b.i.d. after total knee or hip replacement (TKR, THR) surgery (N = 5,510). Renal function, age, gender, and body weight impacted apixaban exposure. Bleeding risk increased as a function of exposure. Predicted bleeding frequencies for TKR and THR populations at risk for high apixaban exposure (female, age > 75 years, calculated creatinine clearance (cCrCL) < 30 ml/min, body weight < 50 kg) (6.85 and 10.3%, respectively) were comparable to the reference population (male/female, age 65-75 years, cCrCL ≥ 80 ml/min, body weight 65-85 kg) (6.18 and 9.32%, respectively). A 100% increase in apixaban exposure is expected to raise bleeding frequencies to 7.25% (TKR) and 10.9% (THR), whereas a 200% increase would raise them to 8.49 and 12.7%. Coexistence of combined patient risk factors or doubling of exposure is not likely to result in a substantial, clinically relevant increase in bleeding risk with 2.5 mg b.i.d. apixaban.

[Personalized molecular medicine: new paradigms in the treatment of cochlear implant and cancer patients]. / Molekulare personalisierte Medizin: Paradigmenwechsel in der Krankenversorgung von Cochlear-Implant- und Tumorpatienten.

OBJECTIVES: To evaluate present options for the indication of cochlear implants (CI) and new forms of treatment for head and neck cancer, melanomas and basal cell carcinomas, with emphasis on future perspectives. METHODS: A literature search was performed in the PubMed database. Search parameters were "personalized medicine", "individualized medicine" and "molecular medicine". RESULTS: Personalized medicine based on molecular-genetic evaluation of functional proteins such as otoferlin, connexin 26 and KCNQ4 or the Usher gene is becoming increasingly important for the indication of CI in the context of infant deafness. Determination of HER2/EGFR mutations in the epithelial growth factor receptor (EGFR) gene may be an important prognostic parameter for therapeutic decisions in head and neck cancer patients. In basal cell carcinoma therapy, mutations in the Hedgehog (PCTH1) and Smoothened (SMO) pathways strongly influence the indication of therapeutic Hedgehog inhibition, e.g. using small molecules. Analyses of c-Kit receptor, BRAF-600E and NRAS mutations are required for specific molecular therapy of metastasizing melanomas. The significant advances in the field of specific molecular therapy are best illustrated by the availability of the first gene therapeutic procedures for treatment of RPE65-induced infantile retinal degradation. CONCLUSION: The aim of personalized molecular medicine is to identify patients who will respond particularly positively or negatively (e.g. in terms of adverse side effects) to a therapy using the methods of molecular medicine. This should allow a specific therapy to be successfully applied or preclude its indication in order to avoid serious adverse side effects. This approach serves to stratify patients for adequate treatment.

[Image guiding techniques and navigation for TACE, SIRT and TIPS]. / Bildführungstechniken und Navigation bei TACE, SIRT und TIPS.

CLINICAL/METHODICAL ISSUE: To avoid non-targeted embolization in liver tumors, arteries important for embolization must be detected. In transarterial chemoembolization (TACE) arteries for particle embolization have to be detected and in selective internal radiotherapy (SIRT) extrahepatic arteries which must be protected from embolization have to be detected. In transjugular intrahepatic portosystemic shunt (TIPS) the problem is to achieve an exactly targeted puncture of the portal vein. STANDARD RADIOLOGICAL METHODS: In TACE and SIRT detection of the vessels is performed from various angles by digital subtraction angiography (DSA). In TIPS puncture is guided by ultrasound or performed blindly. METHODICAL INNOVATIONS: Using cone beam CT (CBCT) very small vessels in the liver can be visualized and 2D-3D back projection is able to detect the exact position of the portal vein in TIPS. ACHIEVEMENTS: The use of CBCT and 2D-3D back projection significantly enhances navigation of vessels. PRACTICAL RECOMMENDATIONS: If flat detector technique is available CBCT should be used in TACE and SIRT and 2D-3D navigation needs hardware and software updates.

Pharmacometric Approaches to Guide Dose Selection of the Novel GPR40 Agonist TAK-875 in Subjects With Type 2 Diabetes Mellitus.

The G-protein-coupled receptor 40 agonist (GPR40) TAK-875 is being developed as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus. Pharmacometric approaches such as model-based exposure-response and meta-analyses were applied to (i) characterize exposure/dose-efficacy responses of TAK-875, (ii) characterize the time course of glycosylated hemoglobin A1c (HbA1c) response with TAK-875 6.25 to 200 mg q.d. doses for 12 weeks, (iii) project and compare HbA1c response with dipeptidyl peptidase 4 (DPP-4) inhibitors and TAK-875 up to 24 weeks, and (iv) provide a quantitative rationale for dose selection in phase 3. On the basis of phase 2 data, relationships between TAK-875 concentrations and HbA1c were well characterized by exposure-response models. EC50 and Emax of TAK-875 were estimated to be 3.16 µg/ml and 0.366, respectively. Model-based simulations over 24 weeks indicated that the 25- and 50-mg q.d. doses of TAK-875 achieve efficacy as comparable with or better than that of commonly used antidiabetic agents.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e22; doi:10.1038/psp.2012.23; advance online publication 9 January 2013.

A Nonlinear Mixed Effects Pharmacokinetic Model for Dapagliflozin and Dapagliflozin 3-O-glucuronide in Renal or Hepatic Impairment.

Dapagliflozin is a sodium-glucose co-transporter 2 inhibitor in development for the treatment of type 2 diabetes mellitus. A semi-mechanistic population pharmacokinetic (PK) model was developed for dapagliflozin and its inactive metabolite dapagliflozin 3-O-glucuronide (D3OG) with emphasis on renal and hepatic contribution to dapagliflozin metabolism. Renal and hepatic impairment decreased the clearance of dapagliflozin to D3OG and the clearance of D3OG. The fraction of D3OG formed via the renal route decreased from 40-55% in subjects with normal renal function (creatinine clearance (CLcr) > 80 ml/min) to 10% in subjects with severe renal insufficiency (CLcr = 13 ml/min). The model-based simulations suggested that the increase of systemic exposure (AUCss) of dapagliflozin and D3OG was less than twofold in subjects with mild or moderate renal impairment. This population modeling analysis presents a useful approach to evaluate the impact of renal and hepatic function on the PK of dapagliflozin.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e42; doi:10.1038/psp.2013.20; advance online publication 8 May 2013.

Correlation from undiluted vitreous cytokines of untreated central retinal vein occlusion with spectral domain optical coherence tomography.

PURPOSE: To correlate inflammatory and proangiogenic key cytokines from undiluted vitreous of treatment-naïve central retinal vein occlusion (CRVO) patients with SD-OCT parameters. METHODS: Thirty-five patients (age 71.1 years, 24 phakic, 30 nonischemic) underwent intravitreal combination therapy, including a single-site 23-gauge core vitrectomy. Twenty-eight samples from patients with idiopathic, non-uveitis floaterectomy served as controls. Interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor (VEGF-A) levels were correlated with the visual acuity (logMar), category of CRVO (ischemic or nonischemic) and morphologic parameters, such as central macular thickness-CMT, thickness of neurosensory retina-TNeuro, extent of serous retinal detachment-SRT and disintegrity of the IS/OS and others. RESULTS: The mean IL-6 was 64.7pg/ml (SD ± 115.8), MCP-1 1015.7 ( ± 970.1), and VEGF-A 278.4 ( ± 512.8), which was significantly higher than the control IL-6 6.2 ± 3.4pg/ml (P=0.06), MCP-1 253.2 ± 73.5 (P<0.0000001) and VEGF-A 7.0 ± 4.9 (P<0.0006). All cytokines correlated highly with one another (correlation coefficient r=0.82 for IL-6 and MCP-1; r=0.68 for Il-6 and VEGF-A; r=0.64 for MCP-1 and VEGF-A). IL-6 correlated significantly with CMT, TRT, SRT, dIS/OS, and dELM. MCP-1 correlated significantly with SRT, dIS/OS, and dELM. VEGF-A correlated not with changes in SD-OCT, while it had a trend to be higher in the ischemic versus the nonischemic CRVO group (P=0.09). CONCLUSIONS: The inflammatory cytokines were more often correlated with morphologic changes assessed by SD-OCT, whereas VEGF-A did not correlate with CRVO-associated changes in SD-OCT. VEGF inhibition alone may not be sufficient in decreasing the inflammatory response in CRVO therapy.

[Cytokine determination from vitreous samples in retinal vascular diseases]. / Zytokinbestimmung aus Glaskörperproben bei retinalen Gefäßerkrankungen.

PURPOSE: The aim of this study was to determine cytokine levels from vitreous samples of treatment-naive patients with diabetic retinopathy (DRP), retinal vein occlusion (RVO) and exudative age-related macular degeneration (ARMD). METHODS: In this study 187 patients (median age 67 years, 101 males) were treated with a combined drug therapy including a 23-gauge core vitrectomy. Interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and intravitreal vascular endothelial growth factor (VEGF-A) levels were determined a using cytometric bead assay (CBA) and compared to those of the control group. RESULTS: Compared to the control group all diseases had significantly elevated cytokine levels, except VEGF in ARMD. In DRP samples of patients with diffuse diabetic macula edema (DME) higher VEGF-A and MCP-1 levels were found than in patients with focal DME. Ischemic DRP had higher VEGF levels than non-ischemic DRP. All measured cytokines were significantly higher in central retinal vein occlusion (CRVO) than in branch retinal vein occlusion (BRVO). CONCLUSIONS: Differences in intravitreal cytokine levels in DRP, RVO and ARMD could be demonstrated. The knowledge of depicted specific characteristic dysregulation of cytokines could allow more targeted future therapies.

Time-varying belatacept exposure and its relationship to efficacy/safety responses in kidney-transplant recipients.

Belatacept is the first T-cell costimulation blocker to be approved for the prophylaxis of organ rejection in adult kidney-transplant recipients (KTRs) and represents an alternative to calcineurin inhibitors, which are known to be nephrotoxic. After transplant, the risk of acute rejection (AR) decreases with time. Accordingly, belatacept exposures were reduced over time by changes in dose and dosing interval in the two treatment regimens tested in two phase III studies. Time-varying belatacept exposures were characterized by developing and applying a population pharmacokinetic model. Clearance and volume of central and peripheral compartments increased with baseline body weight, but there was no effect of age, gender, race, renal/hepatic function, diabetes, patient type (healthy/KTR), or dialysis on belatacept clearance. Exposure-response analyses showed that lower exposures did not compromise efficacy (as measured by AR), whereas higher exposures were associated with increased serious infections and central nervous system events.

Model-based meta-analysis for comparative efficacy and safety: application in drug development and beyond.

High development cost, low development success, cost-disciplined health-care policies, and intense competition demand an efficient drug development process. New compounds need to bring value to patients by being safe, efficacious, and cost-effective as compared with existing treatment options. Model-based meta-analysis (MBMA) facilitates integration and utilization of summary-level efficacy and safety data, providing a quantitative framework for comparative efficacy and safety assessment. This Commentary discusses the application and limitations of MBMA in drug development.

Effect of a high-fat meal on the pharmacokinetics of dapagliflozin, a selective SGLT2 inhibitor, in healthy subjects.

Dapagliflozin is a potent and selective inhibitor of sodium-glucose co-transporter type 2 that is being developed for the treatment of type 2 diabetes mellitus. This open-label, randomized, two-period, two-treatment (single doses of 10-mg dapagliflozin fasted or fed), crossover study was conducted to evaluate the effect of a high-fat meal on the pharmacokinetics of dapagliflozin in 14 healthy subjects. Compared to the fasted state, a high-fat meal decreased mean dapagliflozin maximum plasma concentrations (C(max) ) by 31%, increased the time to C(max) (T(max) ) by 1 h, but did not affect overall dapagliflozin systemic exposure [area under the plasma concentration-time curve (AUC)]. As the cumulative (daily) amount of glucose excreted in the urine induced by dapagliflozin is dependent upon dapagliflozin AUC, the effect of food on dapagliflozin C(max) is unlikely to have a clinically meaningful effect on dapagliflozin's efficacy. On the basis of these findings, dapagliflozin can be administered without regard to meals.

Altered expression of securin (Pttg1) and serpina3n in the auditory system of hearing-impaired Tff3-deficient mice.

INTRODUCTION: Tff3 peptide exerts important functions in cytoprotection and restitution of the gastrointestinal (GI) tract epithelia. Moreover, its presence in the rodent inner ear and involvement in the hearing process was demonstrated recently. However, its role in the auditory system still remains elusive. Our previous results showed a deterioration of hearing with age in Tff3-deficient animals. RESULTS: Present detailed analysis of auditory brain stem response (ABR) measurements and immunohistochemical study of selected functional proteins indicated a normal function and phenotype of the cochlea in Tff3 mutants. However, a microarray-based screening of tissue derived from the auditory central nervous system revealed an alteration of securin (Pttg1) and serpina3n expression between wild-type and Tff3 knock-out animals. This was confirmed by qRT-PCR, immunostaining and western blots. CONCLUSIONS: We found highly down-regulated Pttg1 and up-regulated serpina3n expression as a consequence of genetically deleting Tff3 in mice, indicating a potential role of these factors during the development of presbyacusis.

Lack of pharmacokinetic interaction between dapagliflozin, a novel sodium-glucose transporter 2 inhibitor, and metformin, pioglitazone, glimepiride or sitagliptin in healthy subjects.

AIMS: Dapagliflozin increases urinary glucose excretion by selectively inhibiting renal sodium-glucose transporter 2, an insulin-independent mechanism of action that may be complementary to that of other oral antidiabetes drugs. The current studies assessed the potential for pharmacokinetic (PK) interaction between dapagliflozin and pioglitazone, metformin, glimepiride or sitagliptin in healthy subjects following single-dose administration. METHODS: In open-label, randomized, three-period, three-treatment crossover studies, 24 subjects received 50 mg dapagliflozin, 45 mg pioglitazone or the combination, while 18 subjects received 20 mg dapagliflozin, 1000 mg metformin or the combination. In an open-label, randomized, five-period, five-treatment, unbalanced crossover study, 18 subjects first received 20 mg dapagliflozin, 4 mg glimepiride or the combination, and afterward 100 mg sitagliptin or sitagliptin plus 20 mg dapagliflozin. Blood samples were taken over 72 h of each treatment period. Lack of PK interaction was defined as the ratio of geometric means and 90% confidence interval (CI) for combination:monotherapy being within the range of 0.80-1.25. RESULTS: Co-administration of dapagliflozin with pioglitazone, metformin, glimepiride or sitagliptin had no effect on dapagliflozin maximum plasma concentration (C(max) ) or area under the plasma concentration-time curve (AUC). Similarly, dapagliflozin did not affect the C(max) or AUC for the co-administered drug, except for slight extensions of the 90% CI for the ratio of geometric means for glimepiride AUC (upper limit 1.29) and pioglitazone C(max) (lower limit 0.75). All monotherapies and combination therapies were well tolerated. CONCLUSION: Dapagliflozin can be co-administered with pioglitazone, metformin, glimepiride or sitagliptin without dose adjustment of either drug.

Inflammatory and angiogenic protein detection in the human vitreous: cytometric bead assay.

Introduction. To evaluate clinical feasibility and reproducibility of cytometric bead assay (CBA) in nondiluted vitreous samples of patients with age-related macular degeneration (ARMD), diabetic macular edema (DME), and central retinal vein occlusion (CRVO). Methods. Twelve patients from a single clinics day qualified for intravitreal injections (ARMD n = 6, DME n = 3, CRVO n = 3) and underwent a combination treatment including a single-site 23 gauge core vitrectomy which yielded a volume of 0.6 mL undiluted vitreous per patient. Interleukin-6 (IL-6), vascular endothelial growth factor isoform A (VEGF-A), and monocyte chemo-attractant protein-1 (MCP-1) were assessed directly from 0.3 mL at the same day (fresh samples). To assess the reproducibility 0.3 ml were frozen for 60 days at -80°, on which the CBA was repeated (frozen samples). Results. In the fresh samples IL-6 was highest in CRVO (median IL-6 55.8 pg/mL) > DME (50.6) > ARMD (3.1). Highest VEGF was measured in CRVO (447.4) > DME (3.9) > ARMD (2.0). MCP-1 was highest in CRVO (595.7) > AMD (530.8) > DME (178). The CBA reproducibility after frozen storage was examined to be most accurate for MCP1 (P = 0.91) > VEGF (P = 0.68) > IL-6 (P = 0.49). Conclusions. CBA is an innovative, fast determining, and reliable technology to analyze proteins in fluids, like the undiluted vitreous, which is important to better understand ocular pathophysiology and pharmacology. There is no influence of intermittent storage at -80° for the reproducibility of the CBA.

Quantification of apixaban's therapeutic utility in prevention of venous thromboembolism: selection of phase III trial dose.

A model-based approach was used to integrate data from a phase II study in order to provide a quantitative rationale for selecting the apixaban dosage regimen for a phase III trial. The exposure-response models demonstrated that an increase in daily steady-state area under the plasma concentration-vs.-time curve (AUC(ss)) of 1 microg x h/ml would increase the odds ratio for major bleeding by 0.118 and decrease the odds ratio for venous thromboembolism (VTE) by 0.0499. The therapeutic utility index (TUI) was used to integrate the efficacy and safety predictions to quantify apixaban's efficacy/safety balance as a function of AUC(ss). Of the apixaban dosage regimens tested in phase II, the 2.5 mg twice-daily (b.i.d.) dosage regimen had the highest TUI (86.2%). This was also higher than the TUI for either 30 mg b.i.d. enoxaparin (82.5%) or for warfarin (71.8%). Subjects with moderate renal impairment are expected to have a 43% increase in apixaban exposure; however, apixaban's TUI suggests that dose adjustment is not needed in these subjects with renal impairment.

Dapagliflozin treatment in patients with different stages of type 2 diabetes mellitus: effects on glycaemic control and body weight.

AIM: Dapagliflozin is a stable, competitive, reversible, and highly selective inhibitor of sodium-glucose co-transporter 2, the major transporter responsible for renal glucose reabsorption. With an insulin-independent mechanism of action, dapagliflozin is currently being developed for the treatment of type 2 diabetes mellitus (T2DM). This work aims to compare the efficacy of dapagliflozin, as measured by the change in hemoglobin A1c concentration (A1c) and body weight, and to determine the pharmacodynamic effects of dapagliflozin, as measured by urinary glucose excretion in early-stage and late-stage T2DM patient populations. METHODS: A total of 151 early-stage patients and 58 late-stage patients with T2DM randomly assigned 10 or 20 mg once daily (QD) dapagliflozin treatment or placebo for 12 weeks from two phase 2 studies were included in the analysis. A1c, body weight, and urinary glucose were compared between the two patient populations. RESULTS: Compared with the early-stage population, patients in the late-stage population had a longer duration of T2DM and higher baseline levels of A1c, body weight, fasting plasma glucose, and urinary glucose excretion. After 12 weeks of dapagliflozin treatment, A1c reduction, weight loss, and increased urinary glucose excretion from baseline were observed in both populations. Baseline A1c level impacted the A1c reduction after dapagliflozin treatment with a comparable effect in patients with early and late stage disease. Late-stage patients had greater reduction in body weight. There was no statistically significant difference in the amount of urinary glucose excretion between the early-stage and late-stage patients. CONCLUSIONS: Dapagliflozin treatment at 10 and 20 mg QD for 12 weeks resulted in significant improvement in glycaemic control and body weight reduction in both early-stage and late-stage patients with T2DM. The findings suggest that dapagliflozin could be a promising treatment option for a wide range of patients with T2DM.