Eva Johnsson

Rosuvastatin and Cardiovascular Events in Patients Undergoing Hemodialysis

BACKGROUND Statins reduce the incidence of cardiovascular events in patients at high cardiovascular risk. However, a benefit of statins in such patients who are undergoing hemodialysis has not been proved. METHODS We conducted an international, multicenter, randomized, double-blind, prospective trial involving 2776 patients, 50 to 80 years of age, who were undergoing maintenance hemodialysis. We randomly assigned patients to receive rosuvastatin, 10 mg daily, or placebo. The combined primary end point was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Secondary end points included death from all causes and individual cardiac and vascular events. RESULTS After 3 months, the mean reduction in low-density lipoprotein (LDL) cholesterol levels was 43% in patients receiving rosuvastatin, from a mean baseline level of 100 mg per deciliter (2.6 mmol per liter). During a median follow-up period of 3.8 years, 396 patients in the rosuvastatin group and 408 patients in the placebo group reached the primary end point (9.2 and 9.5 events per 100 patient-years, respectively; hazard ratio for the combined end point in the rosuvastatin group vs. the placebo group, 0.96; 95% confidence interval [CI], 0.84 to 1.11; P=0.59). Rosuvastatin had no effect on individual components of the primary end point. There was also no significant effect on all-cause mortality (13.5 vs. 14.0 events per 100 patient-years; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P=0.51). CONCLUSIONS In patients undergoing hemodialysis, the initiation of treatment with rosuvastatin lowered the LDL cholesterol level but had no significant effect on the composite primary end point of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. (ClinicalTrials.gov number, NCT00240331.)

Dapagliflozin reduces albuminuria in patients with diabetes and hypertension receiving renin-angiotensin blockers

To characterize the effect of dapagliflozin on albuminuria and estimated glomerular filtration rate (eGFR) and to determine whether effects on albuminuria were mediated through changes in glycated haemoblogin (HbA1c), systolic blood pressure (SBP), body weight or eGFR.

Effects of Dapagliflozin on Cardiovascular Risk Factors

Abstract People with diabetes are more likely to develop a cardiovascular (CV) disease compared with those without diabetes. Although effective glycemic control has been the focus of the management of type 2 diabetes mellitus (T2DM), it is also important to control other CV risk factors to improve outcomes in these patients. Dapagliflozin, a sodium-glucose co-transporter 2 inhibitor, lowers glucose levels in patients with T2DM by increasing urinary glucose excretion. Dapagliflozin therapy has been shown to impact a number of CV risk factors. Dapagliflozin improved glycemia with a low intrinsic propensity to cause hypoglycemia. Caloric loss associated with dapagliflozin-induced glucosuria also led to body weight reduction. Small changes from baseline in mean lipid parameters and reductions in serum uric acid levels were observed in patients taking dapagliflozin. Blood pressure reductions were also noted, consistent with modest drug-induced diuresis and weight loss.

Dose‐ranging study with the glucokinase activator AZD1656 in patients with type 2 diabetes mellitus on metformin

To investigate the effect of glucokinase activator AZD1656 on glycated haemoglobin (HbA1c) as an add‐on to metformin in patients with type 2 diabetes.

Durability and tolerability of dapagliflozin over 52 weeks as add-on to metformin and sulphonylurea in type 2 diabetes

To evaluate the safety and efficacy of dapagliflozin as add‐on therapy to metformin plus sulphonylurea over 52 weeks.

Dapagliflozin-induced weight loss affects 24-week glycated haemoglobin and blood pressure levels

The aim of this study was to investigate the associations between dapagliflozin‐mediated reductions in body weight and reductions in glycated haemoglobin (HbA1c) and blood pressure. Data were pooled from seven studies evaluating dapagliflozin 10 mg as monotherapy or combination therapy over 24 weeks. Using linear regression to estimate the contribution of weight loss to HbA1c and blood pressure reductions, the β‐value estimate for HbA1c (%)/kg was 0.028 (p < 0.0001). Weight loss of 2 kg with dapagliflozin contributed to 6% of the total HbA1c reduction. For systolic (SBP) and diastolic blood pressure (DBP), the β‐value (mmHg/kg) estimates were 0.606 (p < 0.0001) and 0.253 (p < 0.0001), respectively. Weight loss of 2 kg contributed to 28% of the overall SBP reduction, and 24% of the overall DBP reduction. In conclusion, dapagliflozin‐mediated weight loss may contribute to overall reductions in HbA1c and blood pressure.

Dapagliflozin lowers blood pressure in hypertensive and non-hypertensive patients with type 2 diabetes

The effect of dapagliflozin on blood pressure was evaluated in non-hypertensive (<140 mm Hg) and hypertensive (⩾140 mm Hg) patients with type 2 diabetes mellitus. Data were pooled from 13 placebo-controlled studies. Patients received dapagliflozin 10 mg/day (n = 2360) or placebo (n = 2295) for up to 24 weeks. Dapagliflozin was associated with placebo-subtracted changes from baseline in systolic and diastolic blood pressures of −3.6 and −1.2 mm Hg, respectively, in hypertensive patients and −2.6 and −1.2 mm Hg, respectively, in non-hypertensive patients. At 24 weeks, a similar proportion of patients experienced measured orthostatic reactions with dapagliflozin versus placebo in hypertensive (6.1% and 6.6%, respectively) and non-hypertensive (4.0% and 4.2%) patients. No clinically relevant difference was observed between dapagliflozin and placebo in heart rate. In conclusion, dapagliflozin 10 mg induces a modest reduction in blood pressure compared with placebo in patients with diabetes with a low risk of orthostatic reactions, regardless of baseline blood pressure.

Efficacy and safety of dapagliflozin in addition to insulin therapy in Japanese patients with type 2 diabetes: Results of the interim analysis of 16‐week double‐blind treatment period

Dapagliflozin treatment when added to insulin therapy in Japanese patients with type 2 diabetes remains to be evaluated.

Efficacy and safety of triple therapy with dapagliflozin add-on to saxagliptin plus metformin over 52 weeks in patients with type 2 diabetes

We previously reported that dapagliflozin versus placebo as add‐on to saxagliptin plus metformin resulted in greater reductions in glycated haemoglobin (A1C), fasting plasma glucose (FPG) and body weight (BW) after 24 weeks of treatment in patients with type 2 diabetes (T2D). Here we report results after 52 weeks of treatment. Patients stabilized on open‐label metformin and saxagliptin 5 mg/day for 8‐16 weeks were randomized to placebo or dapagliflozin 10 mg/day plus open‐label saxagliptin plus metformin for 52 weeks. Changes from baseline to week 52 were greater with dapagliflozin versus placebo in A1C (−0.74% vs. 0.07%), FPG (−27 vs. 10 mg/dL) and BW (−2.1 vs. −0.4 kg). More patients achieved A1C <7% with dapagliflozin (29.4%) versus placebo (12.6%). Adverse events were similar with dapagliflozin (66%) and placebo (71%), and hypoglycaemia was rare (≤2%). Genital infections occurred more often with dapagliflozin (6%) than with placebo (1%); frequency of urinary tract infections was similar between the two groups (9% vs. 10%). Triple therapy with dapagliflozin add‐on to saxagliptin plus metformin is a durable, effective and well‐tolerated intervention for the treatment of T2D.

Dapagliflozin once-daily and exenatide once-weekly dual therapy: A 24-week randomized, placebo-controlled, phase II study examining effects on body weight and prediabetes in obese adults without diabetes.

To explore the effects of dual therapy with dapagliflozin and exenatide on body weight, body composition, glycaemic variables and systolic blood pressure (SBP) in obese adults without diabetes.