Jennifer Sugg

Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.

CONTEXT Dapagliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, reduces hyperglycemia in patients with type 2 diabetes mellitus (T2DM) by increasing urinary glucose excretion, and weight loss is a consistent associated finding. OBJECTIVES Our objectives were to confirm weight loss with dapagliflozin and establish through body composition measurements whether weight loss is accounted for by changes in fat or fluid components. DESIGN AND SETTING This was a 24-wk, international, multicenter, randomized, parallel-group, double-blind, placebo-controlled study with ongoing 78-wk site- and patient-blinded extension period at 40 sites in five countries. PATIENTS Included were 182 patients with T2DM (mean values: women 63.3 and men 58.6 yr of age; hemoglobin A1c 7.17%, body mass index 31.9 kg/m2, and body weight 91.5 kg) inadequately controlled on metformin. INTERVENTION Dapagliflozin 10 mg/d or placebo was added to open-label metformin for 24 wk. MAIN OUTCOME MEASURES Primary endpoint was total body weight (TBW) change from baseline at wk 24. Key secondary endpoints were waist circumference and dual-energy x-ray absorptiometry total-body fat mass (FM) changes from baseline at wk 24, and patient proportion achieving body weight reduction of at least 5% at wk 24. In a subset of patients, magnetic resonance assessment of visceral adipose tissue (VAT) and sc adipose tissue (SAT) volume and hepatic lipid content were also evaluated. RESULTS At wk 24, placebo-corrected changes with dapagliflozin were as follows: TBW, -2.08 kg [95% confidence interval (CI)=-2.84 to -1.31; P<0.0001]; waist circumference, -1.52 cm (95% CI=-2.74 to -0.31; P=0.0143); FM, -1.48 kg (95% CI=-2.22 to -0.74; P=0.0001); proportion of patients achieving weight reduction of at least 5%, +26.2% (95% CI=15.5 to 36.7; P<0.0001); VAT, -258.4 cm3 (95% CI=-448.1 to -68.6; nominal P=0.0084); SAT, -184.9 cm3 (95% CI=-359.7 to -10.1; nominal P=0.0385). In the dapagliflozin vs. placebo groups, respectively, serious adverse events were reported in 6.6 vs. 1.1%; events suggestive of vulvovaginitis, balanitis, and related genital infection in 3.3 vs. 0%; and lower urinary tract infections in 6.6 vs. 2.2%. CONCLUSIONS Dapagliflozin reduces TBW, predominantly by reducing FM, VAT and SAT in T2DM inadequately controlled with metformin.

Long-Term Efficacy of Dapagliflozin in Patients With Type 2 Diabetes Mellitus Receiving High Doses of Insulin: A Randomized Trial

BACKGROUND Dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2, may improve glycemic control with a lower dose of insulin and attenuate the associated weight gain in patients with inadequate control despite high doses of insulin. OBJECTIVE To evaluate the efficacy and safety of adding dapagliflozin therapy in patients whose type 2 diabetes mellitus is inadequately controlled with insulin with or without oral antidiabetic drugs. DESIGN A 24-week, randomized, placebo-controlled, multicenter trial followed by a 24-week extension period. An additional 56-week extension period is ongoing. (ClinicalTrials.gov registration number: NCT00673231) SETTING 126 centers in Europe and North America from 30 April 2008 to 19 November 2009. PATIENTS 808 patients with inadequately controlled type 2 diabetes mellitus receiving at least 30 U of insulin daily, with or without up to 2 oral antidiabetic drugs. INTERVENTION Patients were randomly assigned in a 1:1:1:1 ratio and allocated with a computer-generated scheme to receive placebo or 2.5, 5, or 10 mg of dapagliflozin, once daily, for 48 weeks. MEASUREMENTS The primary outcome was change in hemoglobin A(1c) from baseline to 24 weeks. Secondary outcomes included changes in body weight, insulin dose, and fasting plasma glucose level at 24 weeks and during the 24-week extension period. Adverse events were evaluated throughout both 24-week periods. RESULTS 800 patients were analyzed. After 24 weeks, mean hemoglobin A(1c) decreased by 0.79% to 0.96% with dapagliflozin compared with 0.39% with placebo (mean difference, -0.40% [95% CI, -0.54% to -0.25%] in the 2.5-mg group, -0.49% [CI, -0.65% to -0.34%] in the 5-mg group, and -0.57% [CI, -0.72% to -0.42%] in the 10-mg group). Daily insulin dose decreased by 0.63 to 1.95 U with dapagliflozin and increased by 5.65 U with placebo (mean difference, -7.60 U [CI, -10.32 to -4.87 U] in the 2.5-mg group, -6.28 U [CI, -8.99 to -3.58 U] in the 5-mg group, and -6.82 U [CI, -9.56 to -4.09 U] in the 10-mg group). Body weight decreased by 0.92 to 1.61 kg with dapagliflozin and increased by 0.43 kg with placebo (mean differences, -1.35 kg [CI, -1.90 to -0.80 kg] in the 2.5-mg group, -1.42 kg [CI, -1.97 to -0.88 kg] in the 5-mg group, and -2.04 kg [CI, -2.59 to -1.48 kg] in the 10-mg group). These effects were maintained at 48 weeks. Compared with the placebo group, patients in the pooled dapagliflozin groups had a higher rate of hypoglycemic episodes (56.6% vs. 51.8%), events suggesting genital infection (9.0% vs. 2.5%), and events suggesting urinary tract infection (9.7% vs. 5.1%). LIMITATION Insulin doses were not titrated to target, and the study was not designed to evaluate long-term safety. CONCLUSION Dapagliflozin improves glycemic control, stabilizes insulin dosing, and reduces weight without increasing major hypoglycemic episodes in patients with inadequately controlled type 2 diabetes mellitus. PRIMARY FUNDING SOURCE AstraZeneca and Bristol-Myers Squibb.

Risk factors for Helicobacter pylori resistance in the United States: the surveillance of H. pylori antimicrobial resistance partnership (SHARP) study, 1993-1999.

BACKGROUND: Pretreatment antimicrobial resistance has an important impact on the efficacy of many Helicobacter pylori treatment regimens. OBJECTIVE: To estimate the prevalence of H. pylori resistance to antimicrobials in the United States, to characterize risk factors associated with H. pylori antimicrobial resistance, and to explore the association between drug utilization and antimicrobial resistance patterns over time. DESIGN: Meta-analysis using patient-level data. SETTING: 20 nationwide trials of H. pylori eradication. PATIENTS: 3624 men and women, each of whom contributed one isolate. MEASUREMENTS: Rates of H. pylori resistance to clarithromycin, metronidazole, and amoxicillin, according to geographic region, age, sex, study year, ethnicity, ulcer status, test method, and study. RESULTS: Overall resistance to clarithromycin, metronidazole, and amoxicillin was 10.1% (95% CI, 9.1% to 11.1% [360 of 3571 patients]), 36.9% (CI, 35.1% to 38.7% [1063 of 2883 patients]), and 1.4% (CI, 1.0% to 1.8% [48 of 3486 patients]), respectively. In multivariable analyses, multiple risk factors were associated with resistance to individual agents. Clarithromycin resistance was significantly associated with geographic region (P = 0.050), older age (P < 0.001), female sex (P < 0.001), inactive ulcer disease (P < 0.001), and study (P = 0.010). Metronidazole resistance was significantly associated with female sex (P < 0.001), earlier year of study enrollment (P = 0.036), Asian ethnicity (P < 0.001), use of an epsilometer test (P = 0.002), and study (P < 0.001). Amoxicillin resistance was low and was not significantly associated with any risk factor. In the 1990s, when rates for use of oral macrolides and metronidazole were relatively stable, clarithromycin resistance rates were stable and metronidazole resistance rates varied. CONCLUSIONS: Clinicians should consider risk factors for antimicrobial resistance when deciding which patients should have susceptibility testing and when choosing appropriate H. pylori treatments in the empirical setting.More than half of all days spent in an intensive care unit are incurred by patients older than 65 years of age, and the number of days per year spent in the intensive care unit (per 1000 person-years) is sevenfold higher for persons older than 75 years compared with persons younger than 65 years (1). The population of older persons and their respective proportion of health care expenditures are expected to double by 2030 (2), and some have suggested that we ration the care provided to older patients (3-5). Indeed, physicians in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT) withheld mechanical ventilation at higher rates in older patients, especially in patients 70 years of age or older (6-8). However, previous reports of older patients with respiratory failure from various causes have indicated that recovery and overall prognosis in this age group do not justify using age alone to determine treatment decisions (9-11). Instead, the decision to place older persons with acute lung injury on mechanical ventilation should incorporate several factors, including comorbid illnesses (12), patient preference or previously stated wishes, physician gestalt, and bedside judgment. The incidence of acute respiratory failure requiring mechanical ventilation increases 10-fold from the ages of 55 to 85 years (13), resulting in an increasing number of elderly patients receiving treatment in intensive care units (1, 11, 14). Therefore, health care professionals need to understand the effect of age on outcomes of acute lung injury and the acute respiratory distress syndrome (henceforth called acute lung injury) to guide their treatment decisions and prognostic discussions (15, 16). In most investigations, the mortality rate from acute lung injury has ranged from 40% to 50% (15, 17-21). Data from a large cohort followed from 1983 to 1993 revealed encouraging declines in acute lung injury-related mortality but showed that these improved outcomes were confined largely to patients younger than 60 years of age (22). We used data from an acute lung injury database sponsored by the National Heart, Lung, and Blood Institute (23, 24) to investigate the effect of age on the ability to recover from acute lung injuryinformation that could prove extremely important given the growing number of older persons at risk for acute lung injury (2-5, 16, 25). We hypothesized that age would independently affect acute lung injury outcomes, even after adjustment for severity of illness and other covariates. To investigate this hypothesis, we asked the following questions about age and acute lung injury: 1) How does age affect survival from acute lung injury? 2) Do physiologic recovery and successful liberation from the ventilator take longer in older patients? Methods Patients We examined data on 902 patients who participated in the National Heart, Lung, and Blood Institute multicenter, randomized trials of the Acute Respiratory Distress Syndrome (ARDS) Network between 18 March 1996 and 28 May 1999. Patients were enrolled from 24 hospitals associated with 10 U.S. medical centers. Included in this analysis were the 861 patients from a recently reported randomized trial of mechanical ventilation that compared lower with traditional tidal volume (6 mL/kg of ideal body weight vs. 12 mL/kg of ideal body weight) (24). After the early stopping of the ventilator trial by the data safety monitoring board for efficacy, the 41 additional patients in our analysis had received lisofylline or placebo with the lower tidal-volume strategy. (Lisofylline is a xanthine derivative that decreases the inflammatory response.) The institutional review boards of each participating medical center or hospital approved this study. Patients or their surrogate provided informed consent before enrollment. The study was conducted in accordance with the established ethical standards of the medical centers and with the principles of the Declaration of Helsinki (26). We analyzed age as a binary category and according to decade. To assess the varying effect of age on outcomes, we also used age, coded as a series of indicator variables for decade of age, in multivariable analysis. In keeping with our prospectively defined analysis plan, we decided a priori to report these data as a comparison of the patients younger than 70 years of age (n = 729) with the patients 70 years of age or older (n = 173). In the absence of any clearly defined age cutoff designating patients as elderly, we chose these binary age categories on the basis of data from the SUPPORT studies suggesting that physicians most often used 70 to 75 years of age as a decision-making cut point affecting intensity of care and threshold for withholding mechanical ventilation (6-8). However, additional analyses defining older persons at lower (65 years of age) and higher (80 years of age) cutoffs have yielded similar results. Details of inclusion and exclusion criteria for the ARDS network trials have been reported previously (23, 24). Briefly, patients were eligible if they required mechanical ventilation for acute lung injury, with a partial Po 2 divided by fraction of inspired oxygen of 300 or less, bilateral pulmonary infiltrates consistent with pulmonary edema, and no clinical evidence of left atrial hypertension. If measured, the pulmonary capillary wedge pressure was required to be 18 mm Hg or less (27). The major reasons for exclusion were as follows: more than 36 hours elapsed since the inclusion criteria were met, age younger than 18 years, participation in other acute lung injury trials in the past 30 days, pregnancy, increased intracranial pressure, neuromuscular disease that could impair spontaneous breathing, sickle-cell disease, severe chronic respiratory disease (as previously described [23, 24]), massive obesity, burns covering more than 30% of body surface, comorbid conditions with an estimated 6-month mortality rate greater than 50%, bone marrow or lung transplantation, chronic liver disease (as defined by Child-Pugh Class C [28]), inability to consent, and attending physician refusal or unwillingness to commit full life support. The patients surrogate and managing physician determined whether to withdraw mechanical ventilation, and we analyzed all patient data on an intention-to-treat basis. Protocol for Mechanical Ventilator Management Mechanical ventilation was performed in strict accordance with the ARDS network study protocol (24). Weaning was done according to a protocol that included a daily weaning screen followed by pressure support ventilation and a 2-hour spontaneous breathing trial. The Daily Weaning Screen and Spontaneous Breathing Trials Patients were followed daily to determine when they passed the following weaning screens, which were based on data from previous investigations (29-31): oxygen saturation of at least 0.88 on positive end-expiratory pressure of 8 cm H2O or less and a fraction of inspired oxygen of 0.40 or less, systolic blood pressure of 90 mm Hg or more without vasopressor support, and demonstration of spontaneous inspiratory efforts (initiating breaths above the rate of the ventilator setting). After meeting these daily weaning screen criteria, patients were given a 5-minute trial of spontaneous breathing with continuous positive airway pressure of 5 cm H2O. If the respiratory rate remained 35 breaths/min or less, the patient entered a pressure support weaning protocol and then a 2-hour spontaneous breathing trial on a T-piece or continuous positive airway pressure of 5 cm H2O without pressure support ventilation, as described previously (www.ardsnet.org). The spontaneous breathing trial was terminated if any of the following predetermined conditions were met: respiratory rate greater than 35 breaths/min for more than 5 minutes, sustained arterial oxygen saturation less than 0.90, heart rate that had increased by 20% or more compared with the rate at 0600 hours (6 a.m.), marked use of accessory respiratory muscles, abdominal paradox, marked subjective dyspnea, or diaphoresis. If any of these criteria were met, then the ventilator was set at the patients previously used settings and the patient was weaned by using the pressure-support protocol until the following day, at which time the daily weaning screen would be performed again. Patients passed the spontaneous breathing trial if none of the above conditions were met. After passing the 2-hour spontaneous breathing trial, patients graduated to unassisted breathing, meaning that they were extubated, continued receiving a T-piece, or received continuous positive airway pressure of 5 cm water without pressure support ventilation. Definitions of Recovery Landmarks To determine the rate of recovery of older compared with younger patients, the earliest time at which patients had successfully passed four clearly defined recovery landmarks was recorded: 1) the daily weaning screen, 2) the 2-hour spontaneous breathing trial, 3) the date on which the patient began a period of unassisted breathing that lasted 48 hours or more, and 4) discharge from the intensive care unit alive and with no mechanical ventilation. Severity of Illness Classification and Organ or System Failure Baseline severity of illness was recorded at enrollment by using the Acute Physiology, Age, and Chronic Health Evaluation III (APACHE III) score (32). During analysis, we used a modified APACHE III score that excluded age so that age would remain an independent factor of outcome. Nonpulmonary organ system failures were also recorded by using definitions based on the following objective criteria (24, 33-35): for circulatory failure, a systolic blood pressure of 90 mm Hg or less or the need for treatment with any vasopressor; for coagulation failure, a platelet count of 80 109 cells/L or less; for central nervous system failure, a Glasgow coma scale rating less than 12; for hepatic failure, a serum bilirubin concentration

Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin

Dapagliflozin, a highly selective inhibitor of sodium‐glucose cotransporter 2 (SGLT2), reduces hyperglycaemia and weight in patients with type 2 diabetes mellitus (T2DM) by increasing urinary glucose excretion. Long‐term glycaemic control, body composition and bone safety were evaluated in patients with T2DM after 102 weeks of dapagliflozin treatment.

Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebo-controlled study.

OBJECTIVE To assess the efficacy and safety of dapagliflozin as add-on therapy in patients with type 2 diabetes who were inadequately controlled with a dipeptidyl peptidase-4 inhibitor with or without metformin. RESEARCH DESIGN AND METHODS In this 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 study with a 24-week blinded extension period, 432 patients were randomized to receive dapagliflozin 10 mg/day or placebo added to sitagliptin (100 mg/day) ± metformin (≥1,500 mg/day). RESULTS Baseline HbA1c and FPG levels were 7.9% (63.0 mmol/mol) and 162.2 mg/dL (9.0 mmol/L) for the dapagliflozin group and 8.0% (64.0 mmol/mol) and 163 mg/dL (9.0 mmol/L) for placebo. At week 24, dapagliflozin significantly reduced mean HbA1c levels (–0.5% [–4.9 mmol/mol]) versus placebo (0.0% [+0.4 mmol/mol]). Dapagliflozin reduced body weight versus placebo (–2.1 and –0.3 kg) and reduced HbA1c levels in patients with baseline values ≥8.0% (–0.8% [8.7 mmol/mol] and 0.0% [0.3 mmol/mol]) and fasting plasma glucose levels (–24.1 mg/dL [–1.3 mmol/L] and 3.8 mg/dL [0.2 mmol/L]). Similar results were observed when data were stratified by background therapy. Glycemic and weight benefits observed at week 24 were maintained through week 48. Changes from baseline in systolic blood pressure at week 8 were not significantly different between treatment groups. Over 48 weeks, fewer patients receiving dapagliflozin were discontinued or rescued for failing to achieve glycemic targets compared with placebo. Adverse events were balanced between groups, and discontinuation rates were low. At week 48, signs and symptoms suggestive of genital infection were more frequent with dapagliflozin (9.8%) than with placebo (0.4%). Signs and symptoms suggestive of urinary tract infection were balanced between dapagliflozin (6.7%) and placebo (6.2%). CONCLUSIONS These results suggest that in patients with type 2 diabetes, inadequately controlled on sitagliptin with or without metformin, add-on treatment with dapagliflozin provides additional clinical benefit and is well tolerated.

Dapagliflozin in patients with type 2 diabetes receiving high doses of insulin: efficacy and safety over 2 years.

Dapagliflozin, a selective inhibitor of sodium‐glucose cotransporter 2 (SGLT2), has been shown to improve glycaemic control, stabilize insulin dosing and mitigate insulin‐associated weight gain over 48 weeks in patients whose type 2 diabetes mellitus (T2DM) was inadequately controlled despite high doses of insulin. Here the efficacy and safety of dapagliflozin therapy after a total of 104 weeks are evaluated in this population.

Effect of Helicobacter pylori eradication on development of erosive esophagitis and gastroesophageal reflux disease symptoms: A post hoc analysis of eight double blind prospective studies

OBJECTIVES:The aim of this study was to assess the development of erosive esophagitis, the development of gastroesophageal reflux disease (GERD) symptoms in patients without prior symptomatic or endoscopic GERD, and the worsening of GERD symptoms in patients with prior symptomatic GERD in a post hoc analysis of eight double-blind prospective trials of Helicobacter pylori (H. pylori) therapy in 1165 patients.METHODS:Patients with active or past duodenal ulcer and without baseline erosive esophagitis had end of study endoscopies 4–30 wk after completion of therapy. A total of 533 patients had heartburn and regurgitation scores assessed at baseline and 4 wk after end of therapy, and were divided into two groups: 1) no prior GERD symptoms (n = 127) and 2) prior GERD symptoms (n = 406). H. pylori was assessed at baseline and ≥4 wk after therapy by rapid urease test, histology, and culture.RESULTS:Erosive esophagitis developed in 24 (4%) of 621 patients with cure versus 14 (3%) of 544 with persistent H. pylori (OR = 1.52, 95% CI = 0.78–2.97). In the longest study (28–30-wk follow-up), esophagitis developed in two (7%) of 28 patients with cure versus five (7%) of 76 with persistent infection. New GERD symptoms developed in 13 (14%) of 92 patients with cure versus seven (20%) of 35 with persistent infection (OR = 0.66, 95% CI = 0.24–1.82). GERD worsened in 20 (7%) of 269 with cure vs 20 (15%) of 137 with persistent H. pylori (OR = 0.47, 95% CI = 0.24–0.91; p = 0.02).CONCLUSIONS:Our results do not support the hypothesis that H. pylori eradication in patients with duodenal ulcer disease leads to the development of erosive esophagitis, the development of new symptomatic GERD, or worsening of symptoms in patients with pre-existing GERD.

Esomeprazole-based Helicobacter pylori eradication therapy and the effect of antibiotic resistance: results of three US multicenter, double-blind trials

OBJECTIVES:To determine the efficacy of once-daily esomeprazole plus antibiotics for eradication of Helicobacter pylori, to assess the effect of antibiotic resistance on eradication rate, and to define the rate of emergent resistance.METHODS:Three separate randomized trials were performed in H. pylori–positive patients with a duodenal ulcer or history of documented duodenal ulcer within 5 yrs: 1) esomeprazole (40 mg once daily), amoxicillin (1 g b.i.d.), and clarithromycin (500 mg b.i.d.; this combination will be referred to as EAC) versus esomeprazole (40 mg once daily) plus clarithromycin (500 mg twice daily; this combination will be referred to as EC); 2) EAC versus esomeprazole (40 mg once daily; E); and 3) EC versus E. Therapy was given for 10 days. Endoscopy and biopsies for CLOtest, histology, and culture with susceptibility testing were done at baseline and 4 wk after completion of therapy.RESULTS:Per-protocol and intent-to-treat eradication rates, respectively, were as follows. For EAC versus EC in study 1 (N = 448), 84 versus 55% and 77 versus 52% (p < 0.001); for EAC versus E in study 2 (N = 98), 85 versus 5% and 78 versus 4% (p < 0.001); for EC versus E in study 3 (N = 66), 50% versus 0 and 46% versus 0 (p < 0.05). The 15% of patients in the combined studies with baseline clarithromycin resistance had significantly lower rates of eradication than those with susceptible strains (EAC: 45 vs. 89%; EC: 13 vs. 61%). Emergent resistance was less common after treatment with EAC [2/6 (33%)] than with EC (23/27 [85%]).CONCLUSIONS:Ten-day triple therapy with once-daily esomeprazole plus twice-daily amoxicillin and clarithromycin achieves an eradication rate virtually identical to that of the twice-daily proton pump inhibitor–based triple therapies. Baseline clarithromycin resistance, present in 15% of patients, predicts a markedly decreased rate. Use of an amoxicillin-containing regimen may decrease emergence of clarithromycin resistance.

Vulvovaginitis and balanitis in patients with diabetes treated with dapagliflozin

BACKGROUND Vulvovaginitis, balanitis, and related genital infections are common in patients with type 2 diabetes. Glucosuria, which is an outcome of treatment with sodium glucose cotransporter 2 (SGLT2) inhibitors, is among the possible causes. Dapagliflozin, an SGLT2 inhibitor with demonstrated glycemic benefits in patients with diabetes, has been studied across a broad spectrum of patients. Analysis of multi-trial safety data may better define the relationship between glucosuria and genital infection. METHODS Safety data were pooled from 12 randomized, placebo-controlled Phase 2b/3 trials to analyze the association of glucosuria with genital infection in patients with suboptimally controlled diabetes (HbA1c >6.5%-12%). Patients were randomized to receive dapagliflozin (2.5mg, 5mg, or 10mg) or placebo once daily, either as monotherapy or add-on to metformin, insulin, sulfonylurea, or thiazolidinedione for 12-24weeks. The incidence of clinical diagnoses and of events suggestive of genital infection was evaluated. RESULTS The pooled safety data included 4545 patients: 3152 who received once-daily dapagliflozin (2.5mg [n=814], 5mg [n=1145], or 10mg [n=1193]) as monotherapy or add-on treatment, and 1393 placebo-treated patients. For dapagliflozin 2.5mg, 5mg, 10mg, and placebo, diagnosed infections were reported in 4.1%, 5.7%, 4.8%, and 0.9%, respectively. Most infections were mild or moderate and responded to standard antimicrobial treatment. Discontinuation due to these events was rare. No clear dose-response relationship between dapagliflozin and genital infection was demonstrated. CONCLUSIONS Treatment with dapagliflozin 2.5mg, 5mg, or 10mg once daily is accompanied by an increased risk of vulvovaginitis or balanitis, related to the induction of glucosuria. Events were generally mild to moderate, clinically manageable, and rarely led to discontinuation of treatment.

Dapagliflozin has no effect on markers of bone formation and resorption or bone mineral density in patients with inadequately controlled type 2 diabetes mellitus on metformin

Dapagliflozin, a selective sodium‐glucose cotransporter 2 (SGLT2) inhibitor, reduces hyperglycaemia in patients with type 2 diabetes (T2DM) by increasing urinary glucose excretion. Owing to its mechanism of action, dapagliflozin could potentially affect the renal tubular transportation of bone minerals. Therefore, markers of bone formation and resorption and bone mineral density (BMD) were evaluated in patients with T2DM after 50 weeks of dapagliflozin treatment.