Table 2.
Large randomised controlled cardiovascular outcome trials (CVOTs) in which renal events were measured during treatment of type 2 diabetes patients with an SGLT2 inhibitor. BMI body mass index, CVD cardiovascular disease, eGFR estimated glomerular filtration rate, GLD glucose-lowering drug, MACE major adverse cardiovascular event (cardiovascular death, non-fatal myocardial infarction or stroke), MI myocardial infarction, UACR urine albumin-creatinine ratio. Values for MACE, CV death, MI, stroke, heart failure, all deaths and renal composite are hazard ratio with 95% confidence intervals. *Renal composites varied between trials: EMPA-REG OUTCOMES, doubling of serum creatinine, eGFR ≤ 45 ml/min/1.73 m2, start renal replacement, renal death; CANVAS PROGRAM, > 40% decrease in eGFR, start renal replacement, renal death: DECLARE, > 40% decrease in eGFR, end stage kidney disease, renal or CV death; VERTIS, doubling of serum creatinine, start renal replacement, renal death; CREDENCE, double serum creatinine, end-stage kidney disease, renal death or CV death; SCORED, sustained (> 30 days) decrease of ≥ 50% in eGFR, dialysis and renal transplantation or sustained (> 30 days) eGFR of < 15 ml/min/1.73 m2. **Decline in long-term rate of eGFR
| Patients with type 2 diabetes | ||||||
|---|---|---|---|---|---|---|
| Cardiovascular outcome studies | Renal impairment studies | |||||
| Trial → | EMPA-REG | CANVAS (Program) | DECLARE | VERTIS | CREDENCE | SCORED |
| Agent | Empagliflozin | Canagliflozin | Dapagliflozin | Ertugliflozin | Canagliflozin renal | Sotagliflozin renal |
|
Follow-up (median years) Date of trial end |
3.1 yr 2015 |
2.4 yr 2017 |
4.5 2018 |
3.0 2019 |
2.6 2018 |
1.3 2020 |
| n | 7,020 | 10,142 | 17,160 | 8,246 | 4,401 | 10,584 |
| Age (yr) | 63 | 63.3 | 63.8 | 64.4 | 63.0 | 69 |
| BMI (kg/m2) | 30.6 | 32.0 | 32.1 | 31.9 | 31.3 | 31.8 |
| HbA1c (%) | 8.1 | 8.2 | 8.3 | 8.2 | 8.3 | 8.3 |
| Diabetes duration | 57% > 10y | 13.5y | 11.8y | 13.0y | 15.8y | - |
| Insulin ± GLD (%) | 48 | 50 | 41 | 46.5 | 65.5 | 64 |
| Prior CVD (%) | 100 | 65 | 41 | 100 | 50 | 50 |
| Heart failure (%) | 12 | 11 | 9.9 | 23.4 | 14.8 | 31 |
| MACE |
0.86 0,74, 0.99 |
0.86 0,75, 0.97 |
0.86 0,74, 0.99 |
0.97 0,85, 1.11 |
0.80 0.67, 0.95 |
0.77 0.65, 0.91 |
| CV death |
0.62 0.49, 0.77 |
0.87 0,72, 1.06 |
0.62 0.49, 0.77 |
0.92 0.77, 1.11 |
0.78* 0.61, 1.00 |
0.90 0.73, 1.12 |
| Non-fatal MI |
0.87 0.70, 1.09 |
0.85 0,69, 1.05 |
0.87 0.70, 1.09 |
1.04 0.86, 1.27 |
0.81 0.59, 1.10 |
0.68 0.52, 0.89 |
| Non-fatal stroke |
1.24 0.92, 1.67 |
0.90 0,71, 1.15 |
1.24 0.92, 1.67 |
1.00 0.76, 1.32 |
0.80 0.56, 1.15 |
0.66 0.48, 0.91 |
| Heart failure hospitalisation |
0.65 0.50, 0.85 |
0.67 0,52, 0.87 |
0.65 0.50, 0.85 |
0.70 0.54, 0.90 |
0.61 0.47, 0.80 |
0.67 0.55, 0.82 |
| All death |
0.68 0.57, 0.82 |
0.87 0,74, 1.01 |
0.68* 0.57, 0.82 |
0.93 0.80, 1.08 |
0.83 0.68, 1.02 |
0.99 0.83, 1.18 |
| eGFR range and mean eGFR (ml/min/1.73 m2) |
> 30 74.0 |
> 30 76.5 |
> 60 85.2 |
> 30 76.1 |
30–90 56.2 |
25–60 44.5 |
| Albuminuria UACR mg/g | 17 | 12 | 13 | 19 | 927 | 74 |
| Renal composite* |
0.54 0.70, 0.75 |
0.60 0.47, 0.77 |
0.53 0.43, 0.66 |
0.81 0.63, 1.04 |
0.70 0.59, 0.82 |
0.71 0.46, 1.08 |
| Decreased eGFR decline** | Yes | Yes | Yes | Yes | Yes | Yes |
| Decreased albuminuria | Yes | Yes | Yes | Yes | Yes | Yes |