jardiance: newly approved drug to lower hba1c in type-2 diabetes
DESCRIPTION
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:09/25/2014. Disclosure. I, Rahul Patel, have no conflict of interest to disclose. - PowerPoint PPT PresentationTRANSCRIPT
JARDIANCE:Newly Approved Drug to Lower HbA1C in
Type-2 diabetes
Presented By: Rahul Patel, MS, PharmD. Candidate 2015
Dr. Sam Shimomura, Associate Dean,Western University of Health Sciences
Date:09/25/2014
Disclosure
I, Rahul Patel, have no conflict of interest to disclose.
Objectives
Pharmacists will be able to:
• Describe SGLT2 inhibitors
• Compare available SGLT-2 inhibitors
• Identify ideal candidates for SGLT2 inhibitors
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.
Introduction (Cont’d)
Type 2 diabetes is characterized by 3 factors
• Persistent hyperglycemia
• Impaired β-cell function
• Insulin resistance
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 SGLT1
Currently Approved SGLT2 Inhibitors
Invokana (canagliflozin) Mfg by: Janssen Pharmaceuticals, Inc.Licensed from Mitsubishi Tanabe Pharma CorporationApproved in Mar’2013
Farxiga (dapagliflozin)Mfg By: Bristol-Myers Squib CompanyMkt By: AstraZeneca Pharmaceuticals LPApproved in Jan’2014
Jardiance (empagliflozin)Mfg By: Eli Lilly and CompanyApproved in Aug’2014
Jardiance Efficacy as Monotherapy3
Results at Week 24 From a Placebo-Controlled Monotherapy Study of JARDIANCE
Efficacy in Combination3
Results at Week 24 From a Placebo-Controlled Study for JARDIANCE used in Combination with Metformin
Efficacy in Combination3
Results at Week 24 From a Placebo-Controlled Study for JARDIANCE in Combination
with Metformin and Sulfonylurea
Adverse Effects of Jardiance3
Adverse Reactions Reported in ≥2% of Patients Treated with JARDIANCE and Greater than Placebo in Pooled Placebo-Controlled Clinical Studies of JARDIANCE Monotherapy or Combination Therapy
Hypoglycemia3
Jardiance vs FarxigaJardiance 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/1.73m2, end-stage renal disease, or dialysis: contraindicated
GFR 30 to 60 ml/min/1.73m2: not recommended
GFR ≤ 30 ml/min/1.73m2, 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-glycoprotein
Jardiance vs Farxiga4
Jardiance FarxigaPharmacokinetics 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 transferase
Which SGLT-2 inhibitor to use ?
Efficacy comparison* as monotherapy compared to placebo in 24 weeks trial
Jardiance(10mg,25mg)
Farxiga(5mg,10mg)
Invokana5
(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 trials
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%)
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 diabetes
Current Place in Therapy• FDA 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.
Conclusion• Since 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.
Ideal patientWhich of the following is a candidate for therapy with Jardiance ?
a. A 25 year old pregnant woman with Type 2 diabetes.
b. A 38 year old male, obese patient with Type 2 diabetes
having normal kidney function
c. A 68 year old male patient with Type 2 diabetes.
d. A 25 year old male patient with Type 1 diabetes
References
1.
http://care.diabetesjournals.org/content/early/2013/03/05/d
c12-2625.full.pdf+html
2. 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 insert
Questions ?