FOOTNOTES & REFERENCES:

Overall

*JARDIANCE is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise

- as monotherapy when metformin is considered inappropriate due to intolerance

- in addition to other medicinal products for the treatment of diabetes

For study results with respect to combinations, effects on glycaemic control and cardiovascular events, and the populations studied, see sections 4.4, 4.5 and 5.11

Additional CV protection driven by a significant reduction in death from cardiovascular causes.2 Standard of care included CV medications (ACEIs/ARBs, beta-blockers, statins or antiplatelets/anticoagulants) and glucose-lowering agents given at the discretion of physicians.1,2

CV death

The 38% RRR in CV death was achieved in the overall EMPA-REG OUTCOME® population for the duration of the trial2

Early impact

§ JARDIANCE demonstrated RRR in CV death in adult patients with insufficiently controlled type 2 diabetes (baseline HbA1c 7-10%) and established CV disease (CAD, PAD, or a history of MI or stroke).1,2,7

|| Empagliflozin versus placebo on top of standard of care (included CV medications and glucose-lowering agents given at the discretion of physicians).1,2

Consistency

A post-hoc analysis of data from the EMPA-REG OUTCOME ® trial by baseline HbA1c subgroups.5 EMPA-REG OUTCOME ® was not powered to show differences between subgroups.2,7

** Hazard ratios are related to CV death: HbA1c <7% HR=0.30 (95% CI: 0.12, 0.80); HbA1c 7% to <8% HR=0.59 (95% CI: 0.42, 0.83); HbA1c 8% to <9% HR=0.67 (95% CI: 0.45, 0.99); HbA1c ≥9% HR=0.76 (95% CI: 0.44, 1.31); P=0.4104 for interaction. The subgroup with HbA1c ≥9% had a 95% CI that crossed unity.

Heart failure

†† Heart failure requiring hospitalisation was a secondary CV outcome in the EMPA-REG OUTCOME® trial.2

Safety

‡‡ JARDIANCE is contraindicated in patients with a hypersensitivity to empagliflozin or any of its other components. JARDIANCE should not be used in patients with type 1 diabetes. JARDIANCE should be used with caution in patients who may be at higher risk of ketoacidosis while taking JARDIANCE. For discontinuation of JARDIANCE if DKA is suspected, please see the Full Prescribing Information. JARDIANCE is not recommended in patients with eGFR <60 mL/min/1.73 m2.1

For a complete list of AEs, contraindications, warnings, and precautions, please refer to the Full Prescribing Information.1

§§ Rare cases of DKA, a serious life-threatening condition that requires hospitalisation, including fatal cases, have been reported in postmarketing experience with empagliflozin.1

|||| The incidence of hypoglycaemia was similar to placebo when used as a monotherapy or added to metformin and was increased vs placebo when added to sulphonylurea or insulin (these agents are known to cause hypoglycaemia).1,2

ACEis=angiotensin-converting enzyme inhibitors; AEs=adverse events; ARBs=angiotensin II receptor blockers; CAD=coronary artery disease; CV=cardiovascular; DKA=diabetic ketoacidosis; eGFR=estimated glomerular filtration rate; HR=hazard ratio; MI=myocardial infarction; PAD=peripheral artery disease; RRR=relative risk reduction; HF=heart failure

1. JARDIANCE [summary of product characteristics]. Ingelheim am Rhein, Germany: Boehringer Ingelheim International GmbH; June 2018.

2. Zinman B, Wanner C, Lachin JM, et al; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-2128.

3. Data on file. Boehringer Ingelheim Pharmaceuticals, Inc.

4. Van de Borne, et al. Heart failure hospitalisation or cardiovascular death with empagliflozin in patients with type 2 diabetes and high cardiovascular risk: analysis over time in EMPA-REG OUTCOME®. Poster no. 1119 presented at: European Association for the Study of Diabetes Annual Meeting; September 12-16, 2016; Munich, Germany.

5. Inzucchi SE, Fitchett D, Wanner C, et al. Does baseline HbA1c or change in HbA1c predict the reduction in cardiovascular death with empagliflozin? Results from EMPA-REG OUTCOME®. Poster no. 916 presented at: 53rd Annual Meeting of the European Association for the Study of Diabetes; 11-15 September 2017; Lisbon, Portugal.

6. Kohler S, Zeller C, Iliev H, Kaspers S. Safety and tolerability of empagliflozin in patients with type 2 diabetes: pooled analysis of phase I-III clinical trials. Adv Ther. 2017;34(7):1707-1726.

7. Zinman B, Inzucchi SE, Lachin JM, et al. Rationale, design, and baseline characteristics of arandomized, placebo-controlled cardiovascular outcome trial of empagliflozin (EMPA-REG OUTCOMETM). Cardiovasc Diabetol. 2014;13(102). doi:10.1186/1475-2840-13-102.

* Adult patients with insufficiently controlled type 2 diabetes (HbA1c 7-10%) and coronary artery disease, peripheral artery disease, or a history of myocardial infarction or stroke (event > 2 months).2,3,5

The 38% RRR in CV death was achieved in the overall EMPA-REG OUTCOME® population for the duration of the trial.3

Standard of care included CV medications (ACEIs/ARBs, beta-blockers, statins or antiplatelets/anticoagulants) and glucose-lowering agents given at the discretion of physicians.2,3

§ Pooled data from 10-mg and 25-mg doses of JARDIANCE; both doses showed a comparable reduction in the risk of CV death.3

CV=cardiovascular; RRR=relative risk reduction; HR=hazard ratio; CI=confidence interval; ACEis=angiotensin-converting enzyme inhibitors; ARBs=angiotensin II receptor blockers

1. Piepoli MF, Hoes AW, Agewall S, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice. Eur Heart J. 2016;37(29):2315-2381.

2. JARDIANCE [summary of product characteristics]. Ingelheim am Rhein, Germany: Boehringer Ingelheim International GmbH; June 2018.

3. Zinman B, Wanner C, Lachin JM, et al; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-2128.

4. Van de Borne, et al. Heart failure hospitalisation or cardiovascular death with empagliflozin in patients with type 2 diabetes and high cardiovascular risk: analysis over time in EMPA-REG OUTCOME®;. Poster no. 1119 presented at: European Association for the Study of Diabetes Annual Meeting; September 12-16, 2016; Munich, Germany.

5. Zinman B, Inzucchi SE, Lachin JM, et al. Rationale, design, and baseline characteristics of a randomized, placebo-controlled cardiovascular outcome trial of empagliflozin (EMPA-REG OUTCOMETM). Cardiovasc Diabetol. 2014;13(102). doi:10.1186/1475-2840-13-102.

*Adult patients with insufficiently controlled type 2 diabetes (HbA1c 7-10%) and coronary artery disease, peripheral artery disease, or a history of myocardial infarction or stroke (event > 2 months).1,4,5

Standard of care included CV medications (ACEIs/ARBs, beta-blockers, statins or antiplatelets/anticoagulants) and glucose-lowering agents given at the discretion of physicians.1,4

CI=confidence interval; CV=cardiovascular; HR=hazard ratio; ACEis=angiotensin-converting enzyme inhibitors; ARBs=angiotensin II receptor blockers; RRR=relative risk reduction.

1. Zinman B, Wanner C, Lachin JM, et al; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-2128.

2. Data on file. Boehringer Ingelheim Pharmaceuticals, Inc.

3. Van de Borne, et al. Heart failure hospitalisation or cardiovascular death with empagliflozin in patients with type 2 diabetes and high cardiovascular risk: analysis over time in EMPA-REG OUTCOME®. Poster no. 1119 presented at: European Association for the Study of Diabetes Annual Meeting; September 12-16, 2016; Munich, Germany.

4. JARDIANCE [summary of product characteristics]. Ingelheim am Rhein, Germany: Boehringer Ingelheim International GmbH; June 2018.

5. Zinman B, Inzucchi SE, Lachin JM, et al. Rationale, design, and baseline characteristics of a randomized, placebo-controlled cardiovascular outcome trial of empagliflozin (EMPA-REG OUTCOME™). Cardiovasc Diabetol. 2014;13(102). doi:10.1186/1475-2840-13-102.

* A post-hoc analysis of data from the EMPA-REG OUTCOME® Trial by baseline HbA1c subgroups.2 EMPA-REG OUTCOME® was not powered to show differences between subgroups.1,3

Hazard ratios are related to CV death: HbA1c <7% HR=0.30 (95% CI: 0.12, 0.80); HbA1c 7% to <8% HR=0.59 (95% CI: 0.42, 0.83); HbA1c 8% to <9% HR=0.67 (95% CI: 0.45, 0.99); HbA1c ≥9% HR=0.76 (95% CI: 0.44, 1.31); P=0.4104 for interaction. The subgroup with HbA1c ≥9% had a 95% CI that crossed unity.2

CV = Cardiovascular; HR= Hazard ratio; CI= Confidence interval; ACEis=angiotensin-converting enzyme inhibitors; ARBs=angiotensin II receptor blockers

1. Zinman B, Wanner C, Lachin JM, et al; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-2128.

2. Inzucchi SE, Fitchett D, Wanner C, et al. Does baseline HbA1c or change in HbA1c predict the reduction in cardiovascular death with empagliflozin? Results from EMPA-REG OUTCOME®. Poster no. 916 presented at: 53rd Annual Meeting of the European Association for the Study of Diabetes; 11-15 September 2017; Lisbon, Portugal.

3. Zinman B, Inzucchi SE, Lachin JM, et al. Rationale, design, and baseline characteristics of a randomized, placebo-controlled cardiovascular outcome trial of empagliflozin (EMPA-REG OUTCOMETM). Cardiovasc Diabetol. 2014;13(102). doi:10.1186/1475-2840-13-102.

* Adult patients with type 2 diabetes and CAD, PAD, or a history of MI or stroke.1,2,4

Standard of care included CV medications (ACEIs/ARBs, beta-blockers, statins or antiplatelets/anticoagulants) and glucose-lowering agents given at the discretion of physicians.1,2

Pooled data from 10-mg and 25-mg doses of JARDIANCE; both doses showed a comparable reduction in the risk of hospitalisation for heart failure.2

§ Heart failure requiring hospitalisation was a secondary CV outcome in the EMPA-REG OUTCOME® trial.2

RRR=relative risk reduction; HR=hazard ratio; CI=confidence interval; ACEis=angiotensin-converting enzyme inhibitors; ARBs=angiotensin II receptor blockers; HHF=hospitalisation for heart failure

1. JARDIANCE (Full Prescribing Information). Mexico: Boehringer Ingelheim Pharmaceuticals, Inc; 2017.

2. Zinman B, Wanner C, Lachin JM, et al; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-2128.

3. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Eur J Heart Fail. 2016;18(8):891- 975.

4. Zinman B, Inzucchi SE, Lachin JM, et al. Rationale, design, and baseline characteristics of a randomized, placebo-controlled cardiovascular outcome trial of empagliflozin (EMPA-REG OUTCOMETM). Cardiovasc Diabetol. 2014;13(102). doi:10.1186/1475-2840-13-102.

JARDIANCE is contraindicated in patients with a hypersensitivity to empagliflozin or any of its other components. JARDIANCE should not be used in patients with type 1 diabetes. JARDIANCE should be used with caution in patients who may be at higher risk of ketoacidosis while taking JARDIANCE. For use in renally impaired patients, please refer to the Summary of Product Characteristics. For discontinuation of JARDIANCE if DKA is suspected, please see the Full Prescribing Information.2

JARDIANCE should not be initiated if eGFR is <60 mL/min/1.73 m2 or CrCl is <60 mL/min2
• Should be adjusted to or maintained at 10 mg once daily in patients who tolerate JARDIANCE, whose eGFR falls persistently below 60 mL/min/1.73 m2 or CrCl below 60 mL/min
• Should be discontinued if eGFR is persistently below 45 mL/min/1.73 m2 or CrCl is persistently below 45 mL/min
• Should not be used in patients with ESRD or in patients on dialysis as it is not expected to be effective
For a complete list of AEs, contraindications, warnings, and precautions, please refer to the Full Prescribing Information.

*Data on file, estimated based on ex-factory sales.4

Rare cases of DKA, a serious life-threatening condition that requires hospitalisation, including fatal cases, have been reported in postmarketing experience with empagliflozin.2

Adult patients with insufficiently controlled type 2 diabetes (HbA1c 7-10%) and coronary artery disease, peripheral artery disease, or a history of myocardial infarction or stroke.1-3,5

§Data are for patients who had one or more event and who had received at least one dose of a study drug. All events occurred within 7 days after the last receipt of the study drug.1

||P<0.001 for the comparison with placebo.1

P<0.05 for the comparison with placebo.1

**P<0.01 for the comparison with placebo.1

††A confirmed hypoglycaemic adverse event was a plasma glucose level of less than 70 mg per deciliter (3.9 mmol per liter) or an event requiring assistance.1

‡‡The definition of urinary tract infection was based on 79 preferred terms in the Medical Dictionary for Regulatory Activities (MedDRA). Percentages were calculated as the proportions of all men and all women with the event.1

§§Complicated urinary tract infection was defined as pyelonephritis, urosepsis, or a serious adverse event consistent with urinary tract infection.1

||||The definition of genital infection was based on 88 MedDRA preferred terms. Percentages were calculated as the proportions of all men and all women with the event.1

¶¶The definition of volume depletion was based on 8 MedDRA preferred terms.1

***The definitions of acute renal failure and thromboembolic event were based on 1 standardized MedDRA query for each.1

†††The definition of ketoacidosis was based on 4 MedDRA preferred terms.1

‡‡‡The definition of bone fracture was based on 62 MedDRA preferred terms.1

AEs=adverse events; DKA=diabetic ketoacidosis; HR=hazard ratio

1. Zinman B, Wanner C, Lachin JM, et al; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-2128.

2. JARDIANCE [summary of product characteristics]. Ingelheim am Rhein, Germany: Boehringer Ingelheim International GmbH; June 2018.

3. Kohler S, Zeller C, Iliev H, Kaspers S. Safety and tolerability of empagliflozin in patients with type 2 diabetes: pooled analysis of phase I-III clinical trials. Adv Ther. 2017;34(7):1707-1726.

4.Data on file. Boehringer Ingelheim Pharmaceuticals, Inc.

5. Zinman B, Inzucchi SE, Lachin JM, et al. Rationale, design, and baseline characteristics of a randomized, placebo-controlled cardiovascular outcome trial of empagliflozin (EMPA-REG OUTCOMETM). Cardiovasc Diabetol. 2014;13(102). doi:10.1186/1475-2840-13-102.

PRESCRIBING INFORMATION:

Jardiance 10/25mg film-coated tablets. Active Ingredient: Empagliflozin. Composition: Each tablet contains 10 mg or 25 mg empagliflozin, respectively. Further excipients: Each tablet contains lactose monohydrate microcrystalline cellulose, hydroxypropylcellulose, croscarmellose sodium, colloidal anhydrous silica, magnesium stearate, hypromellose, titanium dioxide (E171), talc, macrogol (400), iron oxide yellow (E172). Therapeutic Indications: Jardiance is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise: as monotherapy when metformin is considered inappropriate due to intolerance and in addition to other medicinal products for the treatment of diabetes. For study results with respect to combinations, effects on glycaemic control and cardiovascular events, and the populations studied, see SmPC sections 4.4, 4.5 and 5.1. Contraindications: Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Undesirable Effects: Very common: Hypoglycaemia (when used with sulphonylurea or insulin). Common: Vaginal moniliasis, vulvovaginitis, balanitis and other genital infection, urinary tract infection (including pyelonephritis and urosepsis), thirst, pruritus (generalised) rash, increased urination, serum lipids increased. Uncommon: urticaria, volume depletion, dysuria, blood creatinine increased/glomerular filtration rate decreased, haematocrit increased. Rare: Diabetic ketoacidosis. Not known: Angioedema, Fournier´s gangrene. Special Warning: Keep out of the sight and reach of children. Further Information: see SmPC, prescription only. Date: February 2019

Pharmaceutical Company: Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Str. 173, 55216 Ingelheim am Rhein, Tel.: 08 00 / 77 90 90 0, Fax: 0 61 32 / 72 99 99, E-Mail: info@boehringer-ingelheim.com

LOADING HEART BASE
CV Death

38%
RELATIVE RISK REDUCTION IN CV DEATH1,2‡

JARDIANCE reduced the risk of CV death on top of CV standard of care1,2†‡

EXAMINE THE DATA
Early Impact

EARLY IMPACT ON RISK REDUCTION OF CV DEATH2-4§‖

Impact on CV death was seen early in the EMPA-REG OUTCOME® trial2-4§‖

EXAMINE THE DATA
Consistency

DATA SUGGESTS SUGGESTS CV DEATH RISK REDUCTION WAS INDEPENDENT OF BASELINE HBA1C2,5 ¶**

CV death reduction was generally consistent across baseline HbA1c5

EXAMINE THE DATA
Heart Failure

RISK REDUCTION OF HOSPITALISATION FOR HEART FAILURE1,2††

JARDIANCE reduced patients’ risk of hospitalisation due to heart failure1,2††

EXAMINE THE DATA
Safety

DEMONSTRATED SAFETY AND TOLERABILITY PROFILE1,2,6‡‡§§

JARDIANCE has demonstrated a positive benefit-risk profile||||

EXAMINE THE DATA

In patients with established CV disease and type 2 diabetes*

JARDIANCE PROVIDED ADDITIONAL CV PROTECTION ON TOP OF STANDARD OF CARE1-5*†

Enter Heart Mode

FOOTNOTES
& REFERENCES

PRESCRIBING INFORMATION

YOU ARE ABOUT TO LEAVE THIS WEBSITE

Using this link will let you leave a website of Boehringer Ingelheim International GmbH (“BI”) or to a different domain under the control of BI. In the event that the linked site is not under the control of BI but under the control of a third party or an affiliate in the Boehringer Ingelheim group of companies, BI shall not be responsible for the contents, processing of personal data of any linked site or any link contained in a linked site, or any changes or updates to such sites. This link is provided to you only as a convenience, and the inclusion of any link does not imply endorsement by BI of the site.

 

Your browser is not supported. This application runs on Chrome, Safari and Firefox. Please use a different browser.