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SODIUM-GLUCOSE COTRANSPORTER TYPE 2 (SGLT2) INHIBITORS

> CANAGLIFLOZIN

STUDY DETAILS

Title: Canagliflozin and renal outcomes in type 2 diabetes and nephropathy [ver Ref. 1].

Year of Publication: 2019

Journal: The New England Journal of Medicine

Study Type: Randomized, double-blind study comparing canagliflozin with placebo.

Sponsored by: Janssen Research and Development

​

Number of Patients: 4,401 (2,202 in the canagliflozin group and 2,199 in the placebo group)

Evaluation Period: Average of 2.62 years

Inclusion Criteria: Patients older than 30 years with type 2 diabetes and nephropathy, with:

  • eGFR of 30–90 ml/min/1.73 m²

  • Albuminuria

  • Glycated hemoglobin (HbA1c) between 6.5% and 12%

  • Treatment with canagliflozin 100 mg/day or placebo

  • Receiving therapeutic doses of renin-angiotensin system inhibitors for at least 4 weeks prior to randomization

Exclusion Criteria: Patients with non-diabetic CKD, type 1 diabetes, those treated with immunosuppressants for kidney disease, or with a history of dialysis or kidney transplantation

​

Patient Characteristics:

  • Average age: 63 years

  • Women: 33.9%

  • Average HbA1c: 8.3%

  • Albumin-to-creatinine ratio: 927

  • eGFR distribution (canagliflozin group):

29.8%: eGFR 30 to <45 ml/min  |  29%: eGFR 45 to <60 ml/min  |  41%: eGFR 60 to <90 ml/min

  • Baseline mean eGFR (canagliflozin group): 56.3 ml/min/1.73 m² (Stage 3a)​

RESULTS

The canagliflozin group had 43.2 events per 1,000 patients per year, compared to 61.2 events in the placebo group. This represents a 30% lower relative risk in the canagliflozin group for the primary composite outcome:

  1. End-stage renal disease

  2. Doubling of serum creatinine

  3. Death from renal or cardiovascular causes

 

Renal Composite Outcome

For the renal-specific composite outcome (ESRD, doubling of creatinine, or death from renal causes), the relative risk was 34% lower in the canagliflozin group:

  • 153/2,202 patients (6.9%) in the canagliflozin group

  • 224/2,199 patients (10.1%) in the placebo group

 

eGFR Findings

The canagliflozin group had an average annual decline of 3.19 ml/min/1.73 m², compared to 4.71 ml/min/1.73 m² in the placebo group, with an intergroup difference of 1.52 ml/min/1.73 m² per year.

Cited References

  1. Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380(24): 2295-2306. https://www.nejm.org/doi/full/10.1056/NEJMoa1811744

  2. Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436-1445. https://www.nejm.org/doi/full/10.1056/NEJMoa2024816

  3. Herrington WG, Staplin N, Wanner C, et al. Empagliflozin in patients with chronic kidney disease. N Engl J Med. 2023;388(2):117-126. https://www.nejm.org/doi/full/10.1056/NEJMoa2204233

> EMPAGLIFLOZIN

STUDY DETAILS

Title: Empagliflozin in patients with chronic kidney disease [see Ref. 3].

Year of Publication: 2023

Journal: The New England Journal of Medicine

Study Type: Randomized, double-blind study comparing empagliflozin with placebo.

Sponsored by: Boehringer Ingelheim

​

Number of Patients: 6,609 (3,304 in the empagliflozin group and 3,305 in the placebo group)

Evaluation Period: Average of 2 years

Inclusion Criteria: Adult patients with or without type 2 diabetes, with chronic kidney disease, with:

  • eGFR of 20–45 ml/min/1.73 m², or

  • eGFR of 45–90 ml/min/1.73 m² with an albumin-to-creatinine ratio ≥200

  • Treated with empagliflozin 10 mg/day or placebo

  • All patients were receiving renin-angiotensin system inhibitors at therapeutic doses

Exclusion Criteria: Patients with polycystic kidney disease or kidney transplantation

​

Patient Characteristics:

  • Average age: 63.8 years

  • Women: 33.2%

  • CKD etiology:

31% diabetes mellitus  |  22% hypertension  |  25% glomerular disease  |  13% other causes  |  9% unknown

  • eGFR distribution (empagliflozin group):

34.2%: eGFR <30 ml/min  |  44.4%: eGFR 30 to <45 ml/min  |  21.4%: eGFR ≥45 ml/min

  • Baseline mean eGFR (empagliflozin group): 37.4 ml/min/1.73 m² (Stage 3b)

RESULTS

In the empagliflozin group, 432 of 3,304 patients (13.1%) experienced one of the composite renal outcomes, compared to 558 of 3,305 patients (16.9%) in the placebo group.

The primary outcome was a composite of kidney disease progression, defined as:

a.1. End-stage renal disease (ESRD)
a.2. Sustained decline in eGFR to <10 ml/min/1.73 m²
a.3. Sustained decline in eGFR ≥40% from baseline
a.4. Death from renal causes

or

b.1. Death from cardiovascular causes

In other terms, the empagliflozin group had 6.8 events per 100 patients per year, compared to 8.9 events in the placebo group.

​

  • Hospitalizations for any cause were lower in the empagliflozin group compared to placebo

  • Empagliflozin reduced the risk of kidney disease progression or cardiovascular death by 28% compared to placebo

 

eGFR Findings

The empagliflozin group had an average annual decline of 2.16 ml/min/1.73 m², compared to 2.92 ml/min/1.73 m² in the placebo group, with an intergroup difference of 0.75 ml/min/1.73 m² per year.

KDIGO 2024 Guidelines

The KDIGO 2024 guidelines recommend treatment with SGLT2 inhibitors for patients with:

  • Type 2 diabetes

  • Chronic kidney disease

  • eGFR >20 ml/min/1.73 m²

as well as for patients without diabetes.

> DAPAGLIFLOZIN

STUDY DETAILS

Title: Dapagliflozin in patients with chronic kidney disease [see Ref. 2].

Year of Publication: 2020

Journal: The New England Journal of Medicine

Study Type: Randomized, double-blind study comparing dapagliflozin with placebo.

Sponsored by: AstraZeneca

​

Number of Patients: 4,304 (2,152 in the dapagliflozin group and 2,152 in the placebo group)

Evaluation Period: Average of 2.4 years

Inclusion Criteria: Patients with or without type 2 diabetes and nephropathy, with:

  • eGFR of 25–75 ml/min/1.73 m²

  • Albumin-to-creatinine ratio of 200–5000

  • Treatment with dapagliflozin 10 mg/day or placebo

​

Patient Characteristics:

  • Average age: 61.8 years

  • Women: 33.1%

  • Albumin-to-creatinine ratio: 949

  • eGFR distribution (dapagliflozin group):

13.6%: eGFR <30 ml/min  |  45.5%: eGFR 30 to <45 ml/min  |  30%: eGFR 45 to <60 ml/min  |  10.9%: eGFR ≥60 ml/min

  • Baseline mean eGFR (dapagliflozin group): 43.2 ml/min/1.73 m² (Stage 3b)

RESULTS

The effect of dapagliflozin was similar in patients with or without type 2 diabetes.

In the dapagliflozin group, 197 of 2,152 patients (9.2%) experienced one of the composite renal outcomes, compared to 312 of 2,152 patients (14.5%) in the placebo group. These outcomes included:

  1. Sustained decline in eGFR of at least 50%

  2. End-stage renal disease (ESRD)

  3. Death from renal causes

  4. Death from cardiovascular causes

 

In other terms, the dapagliflozin group had 4.6 events per 100 patients per year, compared to 7.5 events in the placebo group.

 

eGFR Findings

The dapagliflozin group had an average annual decline of 2.86 ml/min/1.73 m², compared to 3.79 ml/min/1.73 m² in the placebo group, with an intergroup difference of 0.93 ml/min/1.73 m² per year.

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