The EMPA-REG Outcome trial studied the effects of empagliflozin, a SGLT2 inhibitor, on cardiovascular outcomes in patients with type 2 diabetes at high risk of cardiovascular events. Over 7000 patients were randomly assigned to receive empagliflozin 10mg, empagliflozin 25mg or placebo. The primary outcome was a composite of death from cardiovascular causes, nonfatal heart attack or nonfatal stroke. The study found that patients receiving empagliflozin had a lower rate of the primary composite cardiovascular outcome and lower all-cause mortality compared to placebo when added to standard care. Empagliflozin was also associated with weight loss and reduced blood pressure without increased heart rate but risks

1. New England Journal of Medicine
BernardZinman,M.D.,ChristophWanner,M.Detal
September17,2015
EMPA-REG Outcome trial
Empagliflozin,
Cardiovascular Outcomes, and Mortality
in Type 2 Diabetes
-Anirudhya J

2. SGLT2 Inhibitors
• New class of oral anti-diabetic drugs which act by inhibiting
Sodium-glucose transporter 2 in the proximal tubule, thereby
decreasing renal glucose re-absorption and increasing urinary
glucose excretion.
• Includes Canagliflozin, Dapagliflozin and Empagliflozin.
• Empagliflozin was approved by FDA in Aug, 2014.

3. Empagliflozin
Advantages:
• Lower rate of the primary composite cardiovascular
outcome and of death from any cause
• Weight loss and reduction in BP without increase in heart
rate
• Disadvantages :
• Genital infection and UTI
• Not to be used in CKD > Stage 3

4. Aim
To study the effects of empagliflozin in addition to
standard care, on cardiovascular morbidity and
mortality in patients with type 2 diabetes at high
cardiovascular risk.

5. Why this trial ?
• Several health authorities have stressed on the need to
demonstrate cardiovascular safety of new antidiabetes drugs.
• In Sep 2010, US FDA and EMA implemented an immediate
suspension of Rosiglitazone as it was found to have increased
risk of cardiovascular events including acute MI and CVA.

6. • Study population :7020
• Study period : September 2010 - April 2013
• Study place : Multi-centric study conducted in
various hospitals in USA and Europe
• Type of study : Randomized, double-blind, placebo-
controlled trial

7. Inclusion criteria
Eligible patients with type 2 diabetes were :
• Adults (≥18 years of age)
• With a BMI of 45 or less
• Estimated GFR of at least 30 ml per minute per
1.73 m2 of body-surface area.

8. Method
Patients meeting the inclusion criteria were
randomly assigned in a 1:1:1 ratio to receive
1.10 mg Empagliflozin
2.25 mg Empagliflozin
3.Placebo

9. Methodologycontd…
• Background glucose-lowering therapy was to
remain unchanged for the first 12 weeks after
randomization.
• Other cardiovascular risk factors including
dyslipidemia and hypertension were treated
throughout the trial.
• Patients were instructed to attend the clinic at
prespecified times, which included a follow-up
visit 30 days after the end of treatment.

10. Study outcomes
The primary outcome was a composite of death
from cardiovascular causes, nonfatal myocardial
infarction, or nonfatal stroke.
The key secondary outcome was a composite of the
primary outcome plus hospitalization for unstable
angina.

15. Hence we infer
• that the mechanisms behind the cardiovascular
benefits of empagliflozin are multidimensional and
possibly involve changes in arterial stiffness, cardiac
function, and cardiac oxygen demand as well as
cardiorenal effects- reduction in albuminuria,
reduction in uric acid, and established effects on
hyperglycemia, weight, visceral adiposity, and blood
pressure.
• It was observed that genital infection and UTI was
more common in patients treated with empagliflozin.

16. • The proportions of patients with confirmed
hypoglycemic adverse events, acute renal failure,
diabetic ketoacidosis, thromboembolic events, bone
fracture, and events consistent with volume depletion
were similar in the two study groups.

17. Conclusion
Patients with type 2 diabetes at high risk for
cardiovascular events who received empagliflozin,
as compared with placebo, had a lower rate of the
primary composite cardiovascular outcome and of
death from any cause when the study drug was
added to standard care.

18. Thank you