SGLT2 inhibitors and the changing landscape for treatment of diabetes

Figures & data

Table 1 Inclusion criteria and baseline characteristics of EMPA-REG OUTCOME, CANVAS, and DECLARE-TIMI 58

Study	EMPA-REG OUTCOME (2015)^Citation12	CANVAS (2017)^Citation18	DECLARE-TIMI 58 (2018)^Citation19
Medication	Empagliflozin 10–25 mg daily	Canagliflozin 100–300 mg daily	Dapagliflozin 10 mg daily
Study size	n=7,028	n=10,142	n=17,160
Inclusion criteria	T2DM with insufficient glycemic control (drug naïve: A1C=7–9%; on therapy: A1C=7–10%) and high risk of CV events (prior MI, CAD, unstable angina, stroke, or PAD)	T2DM with insufficient glycemic control (A1C=7–10.5%) and either >30 years old with a history of symptomatic CVD or >50 years old with >2 CV risk factors (T2DM >10 years, SBP >140 mmHg on medication; smoking; albuminuria, HDL <1 mmol/L)	T2DM>40 years old, insufficient glycemic control (A1C=6.5–12%), creatinine clearance >60 mL/min and established atherosclerotic disease or multiple risk factors (men >55 years old, women >60 years old, hypertension, dyslipidemia, smoking)
Median follow-up (years)	3.1	2.4	4.2
Mean age (years)	63±9	63±8	64±7
Male (%)	72	64	63
A1C (%)	8.08±0.85	8.2±0.9	8.3±1.2
Insulin use	48	50	41
ASA/Antiplatelet (%)	83	74	61
ACEI/ARB (%)	80	80	81
Statin (%)	77	54	75
Mean GFR (mL/min/1.73 m^2)	74±21	77±21	86±22

Abbreviations: A1C, glycated hemoglobin; ACEI, angiotensin convertase enzyme inhibitor; ARB, angiotensin-receptor blocker; ASA, aspirin; CANVAS, Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes; CAD, coronary artery disease; CV, cardiovascular; CVD, cardiovascular disease; DECLARE-TIMI 58, Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes; EMPA-REG OUTCOME, Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes; GFR, glomerular flow rate; HDL, high-density lipoproteins; MI, myocardial infarction; PAD, peripheral arterial disease; SBP, systolic blood pressure; T2DM, type 2 diabetes mellitus.

Table 2 Study endpoints of EMPA-REG OUTCOME, CANVAS, and DECLARE-TIMI 58

Study	EMPA-REG OUTCOME (2015)^Citation12		CANVAS (2017)^Citation18		DECLARE-TIMI 85 (2018)^Citation19
	Empagliflozin (%)	Placebo (%)	Canagliflozin (%)	Placebo (%)	Dapagliflozin (%)	Placebo (%)
Primary endpoint: CV death, non-fatal MI, or non-fatal stroke	12.1	10.5	2.69	3.15	8.8	9.4
HR (95% CI)	0.86 (0.74–0.99)		0.86 (0.75–0.97)		0.93 (0.84–1.03)
Secondary endpoints
CV death and hospitalization from heart failure	5.7	8.5	16.3	20.8	4.9	5.8
HR (95% CI)	0.66 (0.55–0.79)		0.78 (0.67–0.91)		0.83 (0.73–0.95)
Heart failure	2.7	4.1	5.5	8.7	2.5	3.3
HR (95% CI)	0.66 (0.55–0.79)		0.67 (0.52–0.87)		0.73 (0.61–0.88)
CV death	3.7	5.9	1.2	1.3	2.9	2.9
HR (95% CI)	0.62 (0.49–0.77)		0.87 (0.72–1.06)		0.98 (0.82–1.17)
All-cause death	5.7	8.3	1.2%	1.3%	6.2	6.6
HR (95% CI)	0.68 (0.57–0.82)		0.94 (0.88–1.00)		0.93 (0.82–1.04)

Abbreviations: CANVAS, Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes; CV, cardiovascular; DECLARE-TIMI 58, Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes; EMPA-REG OUTCOME, Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes; HR, hazard ratio; MI, myocardial infarction.

Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373:2117–2128. doi:10.1056/NEJMoa150472026378978

 PubMed Web of Science ®Google Scholar

Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in Type 2 diabetes. N Engl J Med. 2017;377:644–657. doi:10.1056/NEJMoa161192528605608

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Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in Type 2 diabetes. N Engl J Med. 2019;380(4):347–357.

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