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Diabetic nephropathy is one of the comorbidities of diabetic systemic microangiopathy. Therefore, when diabetic nephropathy occurs, it is often accompanied by microangiopathy of other organs or systems such as diabetic retinopathy and peripheral neuropathy. Diabetic nephropathy has now become the second cause of end-stage renal disease, second only to various glomerulonephritis. Type 1 diabetes patients often develop diabetic nephropathy in about 10 to 15 years, while type 2 diabetes patients have a shorter time to develop diabetic nephropathy, which is related to the older age and the combination of other basic diseases. Due to its complex metabolic disorder, once it has developed into end-stage renal disease, it is often more difficult than the treatment of other kidney diseases, so timely prevention and treatment is of great significance to delay diabetic nephropathy.
Recently, Johnson & Johnson's hypoglycemic drug Invokana (canagliflozin, cagliflozin) was approved in the European Union for the treatment of diabetic nephropathy (DKD) in patients with type 2 diabetes (T2D). The drug label will include important renal prognostic data for the milestone CREDENCE trial .
The CREDENCE trial is the first kidney outcome trial specifically for T2D adult patients with DKD. A total of 4401 patients were estimated to have a glomerular filtration rate (eGFR) of 30 to <90mL/min/1.73m2, proteinuria ( Patients with urinary albumin: creatinine ratio> 300 to 5000 mg/g). All patients are receiving DKD standard nursing background treatment.
The results showed that the Invokana group had a significantly lower risk of the primary composite endpoint compared to the placebo group by 30% (composite event rate: 43.2 vs 61.2/1000 patient-years; HR=0.70; 95%CI: 0.57-0.84 ; P <0.0001). The main composite endpoint consisted of end-stage renal disease (ESRD), double serum creatinine, and kidney or cardiovascular (CV) death.
In terms of safety, the incidence of adverse events and serious adverse events was similar between the Invokana group and the placebo group. There was no statistical difference in the incidence of lower limb amputation (HR=1.11) or judgment fracture (HR=0.98). Compared with the placebo group, the risk of diabetic ketoacidosis in the Invokana group was small but increased (HR=10.80, ARR: an increase of 2.0 events/1000 patient-years).
Invokana is a member of the SGLT2 inhibitor family. These drugs work independently of insulin. SGLT2 is a transporter protein involved in glucose reabsorption of the proximal renal tubules. Invokana suppresses SGLT2 expressed in the kidney, reduces the reabsorption of glucose by the kidney, increases the excretion of glucose in the urine, and reduces blood glucose levels. In Europe, Invokana was approved for marketing in 2013 to assist diet and exercise to improve blood glucose control in adult T2D patients.
Diabetes patients are 5 times more likely to need dialysis or kidney transplantation than those without diabetes. Diabetes is the main cause of kidney failure. Therefore, slowing down the rate of DKD progression is critical to the successful treatment of type 2 diabetes and its known comorbidities.
The impressive results from the CREDENCE study have important clinical significance for preventing renal failure. These data have now been incorporated into the world’s leading guidelines for kidney, diabetes, and cardiovascular treatment for millions of patients with chronic kidney disease and type 2 diabetes Provide an opportunity to improve health.
Invokana (canagliflozin) is a type 2 diabetes drug. It belongs to a class of drugs called sodium glucose cotransporter 2 (SGLT2) inhibitors. Some rare but characteristic side effects of Invokana include amputation, diabetic ketoacidosis (too much acid in the blood) and kidney damage.
Invokana slows down the functionality of SGLT2. SGLT2 is a special protein in the kidney. It is responsible for returning 90% of the glucose in the urine to the kidneys.
By slowing down the speed of SGLT2, Invokana can excrete more sugar through the urine. This causes the glucose level in the blood to decrease.
Reference source: Napp Pharmaceuticals Announces European Commission Approval of Invokana (canagliflozin) Label Update to Reflect Improved Renal Outcomes in Patients With Diabetic Kidney Disease and Type 2 Diabetes
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