1. EMPAGLIFLOZIN, CARDIOVASCULAR OUTCOMES, AND MORTALITY IN TYPE 2 DIABETES
Anurag Raghuvanshi and Satyendra K. Rajput
DEPARTMENT OF PHARMCOLOGY, AMITY INSTITUTE OF PHARMACY, EMAIL: anuragraghuvanshi3@gmail.com
ABSTRACT
Empagliflozin is a drug of the gliflozin class, third inhibitor of the sodium-glucose co-transporter 2 approved for the treatment of type 2 diabetes in adults in 2015 which acts by
inhibiting the reabsorption of glucose from proximal tubules (90%) into the bloodstream, leading to excretion of glucose in urine, which also resulted in lowering risk of
mortality (32% reduction) and hospitalization for heart failure (35% reduction), the results obtained during trial clearly show that patient receiving Empagliflozin are at lower
risk of death from cardiovascular causes, non-fatal myocardial infarction or non-fatal stroke compared to the placebo group at significantly higher rates of death from
cardiovascular causes 3.7% vs 5.9% in the placebo group; 38 % relative risk reduction.
Based on the reported study EMPA-REG OUTCOME Investigators (Funded by Boehringer Ingelheim and Eli Lilly), it appears that Empagliflozin could radically change the
way type 2 diabetes is managed.
Keywords:
Diabetes; Empagliflozin; phlorizin; SGLT; SGLT-2 inhibitor; type 2 diabetes, Jardiance
INTRODUCTION
Diabetes mellitus (DM) is the resulting metabolic disorder of diminished produc-
tion, bioavailability and sensitivity of insulin against increased plasma glucose level.
Despite, the presence of numerous anti-hyperglycemic agents, the incidence of
Type2 diabetes mellitus (T2DM) is alarmingly increasing worldwide.
In 2014, 387 million people were estimated to be living with diabetes, an alarming
number that is set to rise to 592 million within the next twenty years. A further 316
million with impaired glucose tolerance are at high risk from the disease, with pro-
jections indicating that over 1 billion people will be living with or at high risk of di-
abetes in 2035.
MECHANISM OF ACTION
Inhibition of renal tubular glucose reabsorption, leading to a reduction in blood
glucose concentration through enhanced urinary glucose excretion, provides a
novel insulin- independent therapy. . SGLT2 is responsible for the absorption of
approx. 80-90% of the filtered glucose load, while remaining 10-20% of filters
glucose is taken up by the SGLT1 transporter , Thus excreting glucose in urine
and subsequent reductions in plasma glucose and glycosylated haemoglobin con-
centrations
REPORTED BY EMPA-REG OUTCOME INVESTIGATORS (Funded by
Boehringer Ingelheim and Eli Lilly)
A total of 7020 patients were treated (median observation time, 3.1 years). The
primary outcome occurred in 490 of 4687 patients (10.5%) in the pooled em-
pagliflozin group and in 282 of 2333 patients (12.1%) in the placebo group
(hazard ratio in the Empagliflozin group, 0.86; 95.02% confidence interval, 0.74
to 0.99; P=0.04 for superiority). There were no significant between-group differ-
ences in the rates of myocardial infarction or stroke, but in the empagliflozin
group there were significantly lower rates of death from cardiovascular causes
(3.7%, vs. 5.9% in the placebo group; 38% relative risk reduction), hospitaliza-
tion for heart failure (2.7% and 4.1%, respectively; 35% relative risk reduction),
and death from any cause (5.7% and 8.3%, respectively; 32% relative risk re-
duction). There was no significant between-group difference in the key second-
ary outcome (P=0.08 for superiority). Among patients receiving empagliflozin,
there was an increased rate of genital infection but no increase in other adverse
events.
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.
REFERENCES
 Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes —
NEJM 2015, 373, 22, 2117-2128, Massachusetts Medical Society
 Diabetes Care June 2014 vol. 37no. 6 1650-1659
METHODS ADOPTED BY EMPA-REG OUTCOME INVESTIGATORS (Funded by
Boehringer Ingelheim and Eli Lilly)
Patients were randomly assigned to receive 10 mg or 25 mg of empagliflozin or
placebo once daily. The primary composite outcome was death from cardiovascular
causes, nonfatal myocardial infarction, or nonfatal stroke, as analyzed in the pooled
empagliflozin group versus the placebo group. The key secondary composite outcome
was the primary outcome plus hospitalization for unstable angina.
LIMITATION
 Empagliflozin may cause dizziness, light-headedness, or fainting; alcohol, hot weath-
er, exercise, or fever may increase these effects. To prevent them, sit up or stand
slowly, especially in the morning. Sit or lie down at the first sign of any of these ef-
fects.
 Be careful not to become dehydrated, especially during hot weather or while you are
being active. Dehydration may increase the risk of empagliflozin's side effects.
 Low blood sugar may occur when it is used along with certain other medicines for
diabetes (e.g., insulin, sulfonylureas).
NUMBER (%) OF PATIENTS
PLACEBO
N=995
JARDIANCE
10 MG
N=999
JARDIANCE 25
MG
N=977
Urinary tract infection 7.6% 9.3% 7.6%
Female genital mycotic infections 1.5% 5.4% 6.4%
Upper respiratory tract infection 3.8% 3.1% 4.0%
Increased urination 1.0% 3.4% 3.2%
Dyslipidemia 3.4% 3.9% 2.9%
Arthralgia 2.2% 2.4% 2.3%
Male genital mycotic infections 0.4% 3.1% 1.6%
Nausea 1.4% 2.3% 1.1%
ADVERSE EFFECT