1. A Brief Review of Jardiance:
An Antidiabetic Agent
Daniel Bediako, Pharm.D Candidate 2015
APPE Preceptor:
Tammy Hart, BS, Pharm.D
Jefferson Community Healthcare Center
March 2015
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2. Presentation Outline
• Introduction
• FDAApproved SGLT-2 Inhibitors
• Mechanism
• Dosage Forms
• Adult Dosing
• Pharmacokinetics
• Evidenced-Based Treatment
• Conclusion
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3. Introduction
• Jardiance
– Approved by FDA in August 2014
– Indication: Type-2 DM
– Manufacturer:
• Boehringer Ingelheim Pharmaceuticals, Inc.
– Pricing (30 tablets): $411.38
• Invokana: $411.41; Farxiga: $411.53
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4. FDAApproved SGLT-2 Inhibitors
Drug Canagliflozin
(Invokana)
Dapagliflozin
(Farxiga)
Empagliflozin
(Jardiance)
MOA inhibits SGLT2 in the proximal tubule increasing urinary glucose
excretion
Strengths Tab: 100 mg, 300 mg 5 mg, 10 mg 10 mg, 25 mg
Adverse Effects Increase LDL-C, weight loss, UTI, constipation, nausea, abdominal
pain, hypoglycemia
Drug Interactions Thiazide diuretics, MAOIs, Atypical antipsychotics
Contraindications GFR less than 45 mL/min, ESRD (Jardiance)
Efficacy About 1% A1c reduction
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5. Mechanism of Action
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6. Available Dosage Forms
http//:www.mims.co.uk,Jardiance:fSGLT2 inhibitor,3/8/2015
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7. Adult Dosing
• Renal Impairment
– eGFR ≥45 mL/minute/1.73 m2: No dosage adjustment necessary.
– eGFR <45 mL/minute/1.73 m2: discontinue therapy when eGFR
is persistently <45 mL/minute/1.73 m2
– eGFR <30 mL/minute/1.73 m2: Use is contraindicated.
– ESRD, dialysis: Use is contraindicated.
• Hepatic Impairment
• no dosage adjustments provided
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8. Pharmacokinetics
• Distribution: Vd: 73.8 L
• Protein binding: 86.2%
• Metabolism: primarily through glucuronidation
• Half-life Elimination: 12.4 hours
• Time to Peak: 1.5 hours
• Excretion: Urine (54.4%; as unchanged drug); feces (41.2%;
majority as unchanged drug)
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9. Brain Teaser
Question:
The active ingredients of Glyxambi are Jardiance and
A. Metformin
B. Linagliptin
C. Sitagliptin
D. Glimepiride
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10. Brain Teaser
Question:
The active ingredients of Glyxambi are Jardiance and
A. Metformin
B. Linagliptin
C. Sitagliptin
D. Glimepiride
Note: Glyxambi 10/5 mg and 25/5 mg
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11. Evidence-Based Treatment
• Title:
• Comparison of empagliflozin and glimepiride as add-on to
metformin in patient with type 2 diabetes: a 104-week
randomized, active controlled, double blind phase 3 trial
(EMPA-REG H2H-SU), Lancet Diabetes Endocrinology
2014,volume 2:691-700
• Source:
– Ridderstråle, M., Andersen, K. R., Zeller, C., Kim, G., Woerle, H. J., & Broedl, U. C. (2014).
Comparison of empagliflozin and glimepiride as add-on to metformin in patients with type 2
diabetes: a 104-week randomised, active-controlled, double-blind, phase 3 trial. The Lancet.
Diabetes & Endocrinology, 2(9), 691-700.
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12. Abstract
• Objective:
• to compare the safety and efficacy of glimepiride and
empagliflozin as a second-line option in type-2 diabetes
patients inadequately controlled on metformin
• Study design:
• A two-year, randomized trial, double-blind, active controlled,
parallel-group,
– Number of Patients: 1549: (Jardiance, n=769)
– Dosage: Jardiance (25 mg PO QD); Glimepiride (1-4
mg PO QD)
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13. Abstract continued
Primary Endpoint
Drug Jardiance Glimepiride
A1c <7% in week 52 267 (39%) 279 (39%)
A1c <7% in week 104 232 (34%) 221 (31%)
Secondary Endpoints:
 Adverse Events: Jardiance (86%), Glimepiride (86%)
o Jardiance (weight and BP reductions, hypoglycemia);
o Glimepiride (weight gain and hypoglycemia)
 Severe Adverse Events: Jardiance (16%), Glimepiride (11%)
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14. Inclusion criteria
• Age ≥ 18 years with type-2 diabetes
• BMI ≤ 45kg/m2
• HbA1c ≥ 7% to ≤ 10%
• Unchanged dose of immediate release metformin ≥ 1500 mg/day
for at least 12 weeks prior to randomization
• Provide written informed consent
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15. Exclusion criteria
• Estimated Glomerular Filtration Rate (eGFR) < 60 ml/min
• Blood Glucose concentration >240 mg/dl
• Use of other antidiabetic drug other than metformin 12 weeks
before trial
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16. Study strengths and weaknesses
• Strenghts
– Long duration
– Few patients lost to follow up
– Randomized trial and active control
– Up titration of glimepiride to half max daily dose as
recommended by ADA
• Weaknesses
– Study funded by Boehringer Ingelheim and Eli Lilly
– Boehringer Ingelheim was involved in study design, data
collection and analysis
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17. Clinical Conclusion
• Empagliflozin is a good second line option that should be
considered in patients who are obese and hypertensive
• Studies have also shown that individuals with type 2 DM lose
their beta cell function as the disease progresses
• Therefore the need for non-insulin dependent antidiabetic drugs is
highly relevant
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18. Personal Conclusion
• Empagliflozin can potentially be used as a second-line option for
patients who have not achieved optimal control with metformin as
a monotherapy
• It could be a good choice for obese patients with uncontrolled
hyperglycemia and hypertension
• BUT, more studies need to be done to address more of the
cardiovascular effects
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19. Works Cited
• Barnett AH. Impact of sodium glucose co-transporter 2(SGLT 2) inhibitors on weight in
patient with type 2 diabetes mellitus. Postgrad Med 2013;125: 92-100
• Lexicomp Online, Lexi-Drugs Online, Hudson, Ohio: Lexi-Comp Inc., 2014 12; August 2014
• Ridderstråle, M., Andersen, K. R., Zeller, C., Kim, G., Woerle, H. J., & Broedl, U. C.
(2014). Comparison of empagliflozin and glimepiride as add-on to metformin in patients
with type 2 diabetes: a 104-week randomised, active-controlled, double-blind, phase 3
trial. The Lancet. Diabetes & Endocrinology, 2(9), 691-700.
• Tikkanen, I., Narko, K., Zeller, C., Green, A., Salsali, A., Broedl, U. C., & Woerle, H. J.
(2015). Empagliflozin reduces blood pressure in patients with type 2 diabetes and
hypertension. Diabetes Care, 38(3), 420-428
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