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Dear Readers! I started this blog when my daughter was in the NICU. She had ventriculitis. Her CSF report grew E.coli. But, she was injected Teicoplanin directly into her brain. The doctors made two errors here:

Teicoplanin is for gram-positive bacteria only. It does not treat E.coli.
Teicoplanin is not for intraventricular use. The manufacturer strongly discourage injecting Teicoplanin into the brain.

My daughter bled into the brain. She lived for another two years and ultimately died.

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Invokana (canagliflozin) in CKD - The CREDENCE Trial

Invokana, the brand name of Canagliflozin, an SGLT2 inhibitor, after decades, has been proven to slow disease progression in Chronic Renal Failure. Diabetic Kidney disease is the leading cause of end-stage renal disease worldwide. The only medical therapy available until now, that has proven benefits in slowing and probably reversing the disease progression are the ACE inhibitors and ARBs. More than half of the patients develop Kidney disease and end up with either hemodialysis or kidney transplantation.

Stages of Diabetic Kidney disease:

Diabetic nephropathy is divided into five stages:

The first stage is Hyperfiltration
The incipient stage follows the stage of hyperfiltration
The stage of microalbuminuria: This is the most important stage as most patients who develop kidney disease are picked up at this stage. It is characterized by albumin to creatinine ratio of 30 to 300 mg/day

The "BAD NEWS" at this stage is that the patient has developed diabetic nephropathy.

However, the "GOOD NEWS" is that at this stage, with good glycemic control and the use of ACE inhibitors or ARBS, the kidney disease can be reversed.

The Stage of Macroalbuminuria characterized by albumin to creatinine ratio of more than 300 mg/ 24 hours. This stage is partially reversible with good glycemic control and the use of ACE inhibitors and ARBs. However, most patients progress to the stage of CKD and ultimately ESRD.
Stage 5 which is the last stage of diabetic nephropathy is characterized by elevated creatinine and reduction in the glomerular filtration rate. Most patients ultimately require Renal Replacement Therapy.

What is Invokana or Canagliflozin?

Invokana is the brand name of canagliflozin. It is an SGLT2 inhibitor that is used to treat patients with type 2 diabetes mellitus.

It inhibits the sodium and glucose reabsorption from the kidney tubules back into the blood. Thus, reducing the blood or plasma sugar levels.

Because of its unique mechanism of action, it is used as monotherapy or as an add-on therapy to metformin, DPP IV inhibitors, sulfonylureas, and Insulin for optimal glycemic control.

Although, theoretically, it can be used in type 1 Diabetes Mellitus as well. However, it is not recommended for use in type 1 DM patients until now because of the risk of euglycemic diabetic ketoacidosis.

Invokana (canagliflozin) reduces mortality and progression to ESRD by 30%!

The CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial evaluated the role of canagliflozin in patients with established Renal disease.

Patients who had an estimated GFR of 30 to 90 ml/min and albuminuria were enrolled in this study. Patients were given either placebo or canagliflozin in addition to standard treatment.

More than 4000 patients were enrolled in the study. The CREDENCE trial was stopped early because the benefits seen with canagliflozin were enormous. There was a 30% reduction in the primary endpoints compared to placebo.

The primary endpoints were:

1. Progression to end-stage renal disease defined as the need for a kidney transplant or hemodialysis
2. Doubling of the creatinine from baseline
3. Death due to cardiovascular or Renal cause.

Secondary endpoints included myocardial infarction, stroke, and hospitalization for heart failure. Compared to placebo, there was also a reduction in the secondary endpoints.

What are the side effects of Invokana/ Canagliflozin?

Like all other SGLT 2 inhibitors (dapagliflozin and empagliflozin), canagliflozin is associated with the following side effects:

It increases the risk of Genital Infections, some of which may be very serious. Serious genital infections include Fournier's gangrene and necrotizing fasciitis.
Dehydration: Since the SGLT2 inhibitors inhibit the reabsorption of sodium and glucose from the renal tubules, more glucose and sodium is lost in the urine. This leads to osmotic diuresis and dehydration.
Euglycemic ketoacidosis: Ketoacidosis is a serious acute complication of diabetes mellitus. Most of the patients who develop ketoacidosis are insulin deficient and have high blood sugars. Patients using SGLT2 inhibitors can develop ketoacidosis despite normal blood sugars.
Acute Renal Failure: Since Invokana may lead to volume loss and dehydration, it may result in renal failure. Patients who are at risk of developing acute renal failure should not be prescribed this medicine.
Bone Fractures: The CANVAS trial that evaluated the safety of canagliflozin in cardiac patients noted an increased risk of fractures in the canagliflozin group. Although, the CREDENCE trial did not show an increased risk of bone fractures with the use of canagliflozin, "the US Boxed Warning" still emphasizes caution in this regard.

In conclusion:

Diabetic kidney disease is a serious disease that affects almost half of diabetic patients. The addition of the newer class of drugs, the SGLT2 inhibitors, have shown promising results in patients with established renal disease. Along with the use of ACE inhibitors and ARBs, the use of Invokana (Canagliflozin) in diabetic patients with kidney disease will further delay the need for renal replacement therapy.

Empagliflozin - Dose, Side effects, contraindications