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

1

Presentation Outline

• Introduction

• FDA Approved SGLT-2 Inhibitors

• Mechanism

• Dosage Forms

• Adult Dosing

• Pharmacokinetics

• Evidenced-Based Treatment

• Conclusion

2

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

3

FDA Approved 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

4

Mechanism of Action

5

Available Dosage Forms

http//:www.mims.co.uk,Jardiance:fSGLT2 inhibitor,3/8/2015

6

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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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)

8

Brain Teaser

Question:

The active ingredients of Glyxambi are Jardiance and

A. Metformin

B. Linagliptin

C. Sitagliptin

D. Glimepiride

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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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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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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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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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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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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

15

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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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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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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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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