Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Volume and market share of anti-epileptic drugs in The Netherlands: impact of new drugs.

Item does not contain fulltextOBJECTIVE: In the past decade, several new anti-epileptic drugs (AEDs) were introduced in The Netherlands. These new drugs, one of which is lamotrigine, are 6 to 10 times more expensive than conventional anti-convulsants. In 1997, the high cost of lamotrigine, together with a lack of clinical data supporting its superiority over conventional drugs, prompted the Dutch Health Insurance Board to release a guideline in which the use of lamotrigine was restricted to difficult-to-treat patients. Other new drugs that were marketed after 1997 also became subject to this guideline. The utilisation of new AEDs and the cost consequences are the subject of this paper. METHODS: Data from extramurally prescribed AEDs was obtained from the Dutch Drug Information Project, which is a database containing prescriptions for about 5.5 million inhabitants of the Netherlands. This data was used to study the impact of new AEDs on volume and market share of AEDs in the period from 1995 to 2001 in The Netherlands. RESULTS: Between 1995 and 2001, the total volume of AEDs increased by 130%, 60% of which consisted of new AEDs. Gabapentin, lamotrigine and oxcarbazepine were the most frequently prescribed new compounds. The volume share of new AEDs increased from 5% in 1995 to 18% in 2001. The market share amounted to 21.5 million euros in 1995 and rose to 47 million euros in 2001; 80% of this increase was due to the introduction of new AEDs. DISCUSSION: Although in 2001 the volume share of new AEDs was still modest, their introduction has led to a strong increase in the cost. New data is emerging on the effectiveness and cost-benefit sum of the new AEDs; this may change the place in therapy of these drugs. Because of their strong potential to force up cost, the positioning of new AEDs requires further attention

An international perspective on preceding infections in Guillain-Barré Syndrome: the IGOS-1000 cohort

Background and objectives: Infections play a key role in the development of Guillain-Barré syndrome (GBS) and have been associated with specific clinical features and disease severity. The clinical variation of GBS across geographical regions has been suggested to be related to differences in the distribution of preceding infections, but this has not been studied on a large scale. Methods: We analysed the first 1000 patients included in the International GBS Outcome Study with available biosamples (n=768) for the presence of a recent infection with: Campylobacter jejuni, hepatitis E virus, Mycoplasma pneumoniae, cytomegalovirus, and Epstein-Barr virus. Results: Serological evidence of a recent infection with C. jejuni was found in 228 (30%), M. pneumoniae in 77 (10%), hepatitis E virus in 23 (3%), cytomegalovirus in 30 (4%) and Epstein-Barr virus in 7 (1%) patients. Evidence of more than one recent infection was found in 49 (6%) of these patients. Symptoms of antecedent infections were reported in 556 patients (72%), and this proportion did not significantly differ between those testing positive or negative for a recent infection. The proportions of infections were similar across continents. The sensorimotor variant and the demyelinating electrophysiological subtype were most frequent across all infection groups, although proportions were significantly higher in patients with a cytomegalovirus and significantly lower in those with a C. jejuni infection. C. jejuni–positive patients were more severely affected, indicated by a lower MRC sum score at nadir (P=0.004), and a longer time to regain the ability to walk independently (P=0.005). The pure motor variant and axonal electrophysiological subtype were more frequent in Asian compared to American or European C. jejuni-positive patients (P<0.001, resp. P= 0.001). Time to nadir was longer in the cytomegalovirus-positive patients (P=0.004). Conclusion: Across geographical regions, the distribution of infections was similar but the association between infection and clinical phenotype differed. A mismatch between symptom reporting and serological results and the high frequency of co-infections, demonstrate the importance of broad serological testing in identifying the most likely infectious trigger. The association between infections and outcome indicates their value for future prognostic models