Newly Approved Drug to Lower HbA1C in Type2 diabetes Presented By Rahul Patel MS PharmD C andidate 2015 Dr Sam Shimomura Associate Dean Western University of Health Sciences ID: 489521
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JARDIANCE:Newly Approved Drug to Lower HbA1C in Type-2 diabetes
Presented By:
Rahul Patel,
MS, PharmD.
C
andidate 2015
Dr. Sam Shimomura, Associate Dean,
Western University of Health Sciences
Date:09/25/2014Slide2
DisclosureI, Rahul Patel, have no conflict of interest to disclose.Slide3
ObjectivesPharmacists will be able to:Describe SGLT2 inhibitors
Compare available SGLT-2 inhibitors
Identify
ideal candidates for SGLT2 inhibitorsSlide4
Introduction1
Diabetes mellitus is a chronic disease often requiring complex treatment regimens to prevent long-term complications.
According to the 2012 statistics from CDC, 29.1 million people have diabetes.
The total direct and indirect estimated cost of the disease in 2014 is 245 billion. Slide5
Introduction (Cont’d)Type 2 diabetes is characterized by 3 factors Persistent hyperglycemia
Impaired
β
-cell function
Insulin resistanceSlide6
SGLT2 Inhibitors: A Novel Class2
Sodium-Glucose Co-transporter 2 (SGLT-2) inhibition works directly on glucose, independent of
β
-cell function and insulin
90% of the glucose is reabsorbed by SGLT2 , remaining 10% by SGLT1Slide7
Currently Approved SGLT2 InhibitorsInvokana (canagliflozin)
Mfg by: Janssen Pharmaceuticals, Inc.
Licensed from Mitsubishi Tanabe
Pharma
Corporation
Approved in Mar’2013
Farxiga
(
dapagliflozin
)
Mfg By: Bristol-Myers Squib Company
Mkt
By: AstraZeneca Pharmaceuticals LP
Approved in Jan’2014
Jardiance
(
empagliflozin
)
Mfg By: Eli Lilly and Company
Approved in Aug’2014 Slide8
Jardiance Efficacy as Monotherapy3
Results at Week 24 From a Placebo-Controlled Monotherapy Study of JARDIANCESlide9
Efficacy in Combination3Results at Week 24 From a Placebo-Controlled Study for JARDIANCE used in
Combination with MetforminSlide10
Efficacy in Combination3Results at Week 24 From a Placebo-Controlled Study for JARDIANCE in Combination
with Metformin and Sulfonylurea
Slide11
Adverse Effects of Jardiance3Adverse Reactions Reported in ≥2% of Patients Treated with JARDIANCE and Greater than Placebo in Pooled Placebo-Controlled Clinical Studies of JARDIANCE Monotherapy or Combination TherapySlide12
Hypoglycemia3Slide13
Jardiance vs Farxiga
Jardiance
Farxiga
Indication
As an adjunct to diet and exercise to improve
glycemic
control in adults with T2DM
As an adjunct to diet and exercise to improve
glycemic
control in adults with T2DM
Usual Dose
Starting dose: 10 mg by mouth daily
Maximum dose: 25 mg once daily
Starting dose: 5 mg by mouth daily
Maximum dose: 10 mg once daily
Dosing In Renal Impairment
GFR ≤ 45 ml/min/1.73m
2
,
end-stage renal disease, or dialysis: contraindicated
GFR 30 to 60 ml/min/1.73m
2
: not recommended
GFR ≤ 30 ml/min/1.73m
2
, end-stage renal disease, or dialysis: contraindicated
Dosing In Hepatic Impairment
No dosage adjustment necessary
Use is not recommended in severe hepatic impairment (has not been studied)
Drug Interactions
Insulin or Insulin Secretagogues: increases risk of hypoglycemia
No significant drug interactions
Administration
Take in the morning, with or without food
Take in the morning, with or without food
Metabolism
Primarily metabolized by UGT2B7, UTG1A3, UGT1A8, and UGT1A9
Primarily metabolized by UGT1A9 to an inactive
metabolite
Weak
substrate of P-glycoproteinSlide14
Jardiance vs Farxiga4
Jardiance
Farxiga
Pharmacokinetics
Onset of action: within 24 hours
Protein binding: 86.2%; not affected by renal or hepatic impairment
Oral bioavailability:
79%
Half-life elimination: 12.4 hours
Excretion: urine (54.4%; half as unchanged drug); feces (41.2%, primarily unchanged drug)
Onset of action: within 24 hours
Protein binding: 91%; not affected by renal or hepatic impairment
Oral bioavailability: 78%
Half-life elimination: 12.9 hours
Excretion: urine (75%; <2% as unchanged drug); feces (21%, 15% as unchanged drug)
Most common Adverse Reactions (Frequency)
Female genital infection (6.4% - 5.4%)
Urinary tract infection (7.6% - 9.3%)
Upper respiratory tract infections (4.0% - 3.1%)
Increased urination (3.4% - 3.2%)
Female genital infection (6.9% - 8.4%)
Urinary tract infection (4.3% - 5.7%)
Price
10 mg or 25 mg (30): $361.06
5 mg or 10 mg (30): $347.04
UGT enzyme inducers include
rifampin
,
phenytoin
,
phenobarbital
, and
ritonavir
.
UGT =
uridine
glucuronyl
transferaseSlide15
Which SGLT-2 inhibitor to use ?Efficacy comparison* as monotherapy
compared to placebo in 24 weeks trial
Jardiance
(10mg,25mg)
Farxiga
(5mg,10mg)
Invokana
5
(100mg,300mg)
HbA1C
reduction (%)
0.7-0.9
0.5-0.7
0.91-1.16
FPG reduction (mg/
dL
)
31-36
19.9-24.7
36-43
Weight Loss (in Kg)
2.5-2.8
2.8-3.2
2.2-3.3
SBP reduction (mmHg)
2.6-3.4
2.3-3.6
3.7-5.4
*
Note: comparison in individual trials and not in head to head clinical trialsSlide16
Which SGLT-2 inhibitor to use ?Farxiga :
Carries a warning of Bladder cancer risk.
Newly diagnosed Bladder cancer has been reported in 0.17% of subjects
Use not recommended in Hepatic Impairment (not
studied )
Jardiance
:
Can be used in Hepatic Impairment
Invokana
:
Use not recommended in Hepatic Impairment( not studied)
Dose related
Hyperkalemia
>5.4mEq/
mL
(12%-27%), ≥6.5mEq/
mL
(2%)Slide17
Effects of SGLT-2 inhibitorsBenefits:HbA1C decrease 0.5-1%
Weight Loss
No edema
Once a day dosing
A little decrease of SBP
Minimal Hypoglycemia
Drawbacks
:
UTI,
balanitis
,
mycotic
vulvovaginal
infection
Mild transient decrease in
eGFR
Not studied in Type 1 diabetesSlide18
Current Place in TherapyFDA approved as adjunct to diet and exercise to control blood glucose.
Also studied in combination with
metformin
, SU, insulin,
pioglitazone
Can be used as second line, after
metformin
( because
metformin
is more studied and approved as first line), however, its cost should be considered.Slide19
ConclusionSince the mechanism of action is independent of the insulin and β-cell function, theoretically it can be used as long as renal function is okay.
It is a new drug ,therefore should be used with extra monitoring, renal function especially.
Long term effects unknown
No studies have been done to see that if the decrease in HbA1C correlates with the decrease in macro and micro vascular complications associated with diabetes.Slide20
Ideal patientWhich of the following is a candidate for therapy with Jardiance ?
A 25 year old pregnant woman with Type 2 diabetes.
A 38 year old male, obese patient with Type 2 diabetes having normal kidney function
A 68 year old male patient with Type 2 diabetes.
A 25 year old male patient with Type 1 diabetesSlide21
References1. http://care.diabetesjournals.org/content/early/2013/03/05/dc12-2625.full.pdf+html2. Ele
Ferrannini
& Anna
Solini
,
SGLT2
inhibition in diabetes mellitus: rationale and clinical prospects
,
Nature Reviews Endocrinology
8, 495-502 (August 2012)
3.
Jardiance
package insert
4.
Farxiga
package insert
5.
Invoka
package insertSlide22
Questions ?