Anna Maria Langkilde

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.

Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with glimepiride: a randomized, 24‐week, double‐blind, placebo‐controlled trial

Aims: Progressive deterioration of glycaemic control in type 2 diabetes mellitus (T2DM) often requires treatment intensification. Dapagliflozin increases urinary glucose excretion by selective inhibition of renal sodium‐glucose cotransporter 2 (SGLT2). We assessed the efficacy, safety and tolerability of dapagliflozin added to glimepiride in patients with uncontrolled T2DM.

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 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.

Efficacy and safety of dapagliflozin as a monotherapy for type 2 diabetes mellitus in Japanese patients with inadequate glycaemic control: a phase II multicentre, randomized, double-blind, placebo-controlled trial.

Dapagliflozin is a selective sodium‐glucose co‐transporter 2 (SGLT2) inhibitor under development as a treatment for type 2 diabetes mellitus (T2DM). This study assessed the efficacy and safety of dapagliflozin monotherapy in Japanese T2DM patients with inadequate glycaemic control.

Durability of glycaemic efficacy over 2 years with dapagliflozin versus glipizide as add‐on therapies in patients whose type 2 diabetes mellitus is inadequately controlled with metformin

To assess the long‐term glycaemic durability, safety and tolerability of dapagliflozin versus glipizide as add‐on therapies in patients with type 2 diabetes inadequately controlled by metformin alone.

Efficacy and safety of dapagliflozin monotherapy in Japanese patients with type 2 diabetes inadequately controlled by diet and exercise.

To evaluate the efficacy and safety of the selective sodium glucose co‐transporter 2 inhibitor dapagliflozin in Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled by diet and exercise.

Herring ( Clupea harengus) intake influences lipoproteins but not inflammatory and oxidation markers in overweight men.

Fish consumption is associated with a lower incidence of CVD and decreases in risk factors for atherosclerosis. Although fish contains other interesting components than fish oil, few studies focus on total fish composition and the influence food preparation might have on health-beneficial components. In the present cross-over intervention study the effect of a 6-week herring diet compared with a reference diet on CVD risk factors was investigated. Thirty-five healthy, but overweight, men (mean BMI 28.3 kg/m2) were randomised to a 6-week herring diet (150 g baked herring fillets/d, 5 d/week) or a reference diet (150 g baked lean pork and chicken fillets/d, 5 d/week). Diets were switched after a 12-week washout period. Plasma total cholesterol, TAG, HDL, HDL2, HDL3, LDL, C-reactive protein, IL-6, IL-18, intercellular adhesion molecule-1, oxidised LDL, oxygen radical absorbance capacity using perchloric acid (ORACPCA), whole-blood fatty acids, bleeding time and blood pressure were measured at the beginning and end of each dietary period. HDL was significantly higher after the herring diet period compared with after the reference diet period: 1.04 v. 0.99 mmol/l. TAG decreased after both diets, with no significant difference between the two diets. ORACPCA values did not indicate lower concentrations of non-protein plasma antioxidants, and oxidised LDL was not higher after the herring diet than after the reference diet. To conclude, a 6-week herring-rich diet significantly raised HDL compared with a diet of matched lean pork and chicken dishes. No adverse effects on in vivo oxidation or serum antioxidants were found after herring intake.

Effect of Tenapanor on Serum Phosphate in Patients Receiving Hemodialysis

Hyperphosphatemia is common among patients with CKD stage 5D and is associated with morbidity and mortality. Current guidelines recommend lowering serum phosphate concentrations toward normal. Tenapanor is a minimally absorbed small molecule inhibitor of the sodium/hydrogen exchanger isoform 3 that functions in the gut to reduce sodium and phosphate absorption. This randomized, double-blind, placebo-controlled trial assessed the effects of tenapanor on serum phosphate concentration in patients with hyperphosphatemia receiving hemodialysis. After a 1- to 3-week washout of phosphate binders, we randomly assigned 162 eligible patients (serum phosphate =6.0 to <10.0 mg/dl and a 1.5-mg/dl increase from before washout) to one of six tenapanor regimens (3 or 30 mg once daily or 1, 3, 10, or 30 mg twice daily) or placebo for 4 weeks. The primary efficacy end point was change in serum phosphate concentration from baseline (randomization) to end of treatment. In total, 115 patients (71%) completed the study. Mean serum phosphate concentrations at baseline (after washout) were 7.32-7.92 mg/dl for tenapanor groups and 7.87 mg/dl for the placebo group. Tenapanor provided dose-dependent reductions in serum phosphate level from baseline (least squares mean change: tenapanor =0.47-1.98 mg/dl; placebo =0.54 mg/dl; P=0.01). Diarrhea was the most common adverse event (tenapanor =18%-68%; placebo =12%) and frequent at the highest tenapanor doses. In conclusion, tenapanor treatment resulted in statistically significant, dose-dependent reductions in serum phosphate concentrations in patients with hyperphosphatemia receiving hemodialysis. Additional studies are required to clarify the optimal dosing of tenapanor in patients with CKD-related hyperphosphatemia.

Changes in weight loss-related quality of life among type 2 diabetes mellitus patients treated with dapagliflozin

This study evaluated change in health‐related quality of life (HRQOL) associated with ongoing weight change among patients with type 2 diabetes mellitus (T2DM) treated with dapagliflozin, a highly selective sodium‐glucose cotransporter 2 (SGLT2) inhibitor that lowers blood glucose by increasing urinary glucose excretion and is associated with body weight reductions.