Patients with type 2 diabetes receiving Invokana experienced 30% and 20% lower rates of kidney disease progression and cardiovascular events respectively, when compared to the placebo group.

Results were so obvious and significant that the study was terminated early. About 4500 subjects with DM2 were followed for about 2.5 years. No increased rates of fractures or amputations were seen with Invokana.

Dr. Tashko

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Credence

April 2019

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 CKD to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo.

All patients had an eGFR of 30-90 and albuminuria 300-5,000 mg/day and were treated with renin–angiotensin system blockade.

CV death, MI, or stroke (HR, 0.80; p=0.01)
Hospitalization for heart failure (HR, 0.61; 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.

Primary outcome was a composite of ESRD (dialysis, transplantation, or a sustained estimated GFR of <15), a doubling of the serum creatinine level, or death from renal or cardiovascular causes.

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 (HR, 0.70; 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% (HR, 0.66; p<0.001)
The relative risk of end-stage kidney disease was lower by 32% (HR, 0.68; p=0.002).
The canagliflozin group also had a lower risk of:
- CV death, MI, or stroke (HR, 0.80; p=0.01)
- Hospitalization for heart failure (HR, 0.61; p<0.001).
There were no significant differences in rates of amputation or fracture.