FOR ADULT PATIENTS WITH TYPE 2 DIABETES, ALONG WITH DIET AND EXERCISE
The power of 2
active ingredients
in 1 pill
active ingredients
in 1 pill
Only SYNJARDY XR combines Jardiance® (empagliflozin) tablets with metformin
extended-release into multiple oral dosing options for adult patients with type 2 diabetes who need additional glycemic control along with diet and exercise. SYNJARDY XR is not recommended in patients with type 1 diabetes.
SYNJARDY XR is proven to reduce A1C, along with diet and exercise, as early as 24 weeks. In addition, some patients experienced weight and SBP reductions when taking empagliflozin, a component of SYNJARDY XR.*
Additionally, a study showed empagliflozin, a component of SYNJARDY XR, reduced risk of CV death in adults with type 2 diabetes and established CV disease by 38% (2.2% ARR).1
*SYNJARDY XR is not indicated for weight loss or blood pressure reduction. Changes in weight and SBP were
secondary endpoints.
Add-on to metformin trial design:
A Phase III, randomized, double-blind, placebo-controlled, parallel-group, efficacy and safety study of JARDIANCE (10 mg, 25 mg) administered orally once daily over 24 weeks in patients with type 2 diabetes mellitus with insufficient glycemic control despite treatment with metformin ≥1500 mg alone. Six hundred thirty-seven treated patients received placebo + metformin (N=207), JARDIANCE 10 mg + metformin (N=217), or JARDIANCE 25 mg + metformin (N=213). The primary endpoint was A1C change from baseline. Weight change and blood pressure change from baseline were secondary endpoints.
Empagliflozin initial combination with metformin:
A randomized, double-blind, active-controlled study to evaluate the efficacy and safety of empagliflozin in combination with metformin as initial therapy compared to the corresponding individual components over 24 weeks in adult patients with type 2 diabetes (N=1364). Treatment-naïve patients with inadequately controlled type 2 diabetes entered an open-label placebo run-in for 2 weeks. At the end of the run-in period, patients who remained inadequately controlled and had A1C between 7% and 10.5% were randomized to one of 8 active-treatment arms: empagliflozin 10 mg (N=169) or 25 mg (N=163); metformin hydrochloride 1000 mg (N=167) or 2000 mg (N=162); empagliflozin 10 mg in combination with metformin hydrochloride 1000 mg (N=161) or 2000 mg (N=167); or empagliflozin 25 mg in combination with metformin hydrochloride 1000 mg (N=165) or 2000 mg (N=169).
EMPA-REG OUTCOME trial:
A prospective study designed to investigate CV outcomes. It was not a treat-to-target study designed to evaluate glucose lowering. Investigators were encouraged to manage CV risk factors and blood glucose by actively adjusting all medications in order to achieve appropriate treatment goals in all treatment groups.
A randomized, double-blind, parallel-group trial comparing the risk of experiencing a major adverse cardiovascular event between JARDIANCE and placebo when these were added to and used concomitantly with standard of care treatments for type 2 diabetes and cardiovascular disease. A total of 7020 patients were treated (JARDIANCE 10 mg [N=2345]; JARDIANCE 25 mg [N=2342]; placebo [N=2333]) and followed for a median of 3.1 years. All patients had established atherosclerotic cardiovascular disease at baseline, including one or more of the following: a documented history of coronary artery disease, peripheral artery disease, myocardial infarction, or stroke. The primary outcome was reduction in risk of cardiovascular events, defined by the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.
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†
Source: Fingertip Formulary, health plan or state listed above, and/or data on file, Boehringer Ingelheim Pharmaceuticals, Inc. as of 10/23/2022. Placement on formulary does not establish clinical comparability of products, including safety and efficacy, and is not a guarantee of full or partial coverage and/or payment. Contact health plan, state, or www.medicare.gov for most current information, as it may change without notice. This is not intended to be an exhaustive list of all plans in your area. Boehringer Ingelheim Pharmaceuticals, Inc. and Lilly USA, LLC do not sponsor or endorse any particular plan, and the company/plan names listed do not imply their endorsement of Boehringer Ingelheim Pharmaceuticals, Inc., Lilly USA, LLC, or the product(s) referenced.
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‡
Percentage of covered lives represent a weighted average of both commercial and Part D availability. “Patients” consists of commercially and Medicare Part D insured lives.
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ARR=absolute risk reduction; CV=cardiovascular; SBP=systolic blood pressure.
JARDIANCE is indicated to reduce the risk of cardiovascular (CV) death and hospitalization for heart failure in adults with heart failure; to reduce the risk of sustained decline in eGFR, end-stage kidney disease, CV death, and hospitalization in adults with chronic kidney disease at risk of progression; to reduce the risk of CV death in adults with type 2 diabetes mellitus and established CV disease; as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus.
JARDIANCE is not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus. It may increase their risk of diabetic ketoacidosis.
JARDIANCE is not recommended for use to improve glycemic control in patients with type 2 diabetes mellitus with an eGFR <30 mL/min/1.73 m2. JARDIANCE is likely to be ineffective in this setting based upon its mechanism of action.
JARDIANCE is not recommended for the treatment of chronic kidney disease in patients with polycystic kidney disease or patients requiring or with a recent history of intravenous immunosuppressive therapy or greater than 45 mg of prednisone or equivalent for kidney disease. JARDIANCE is not expected to be effective in these populations.
SYNJARDY is indicated as adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus.
SYNJARDY XR is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Empagliflozin, when used as a component of SYNJARDY or SYNJARDY XR, is indicated in adults with type 2 diabetes mellitus to reduce the risk of:
- Cardiovascular death in adults with established cardiovascular disease
- Cardiovascular death and hospitalization for heart failure in adults with heart failure
SYNJARDY and SYNJARDY XR are not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus. It may increase their risk of diabetic ketoacidosis.
Because of the metformin component, the use of SYNJARDY or SYNJARDY XR is limited to patients with type 2 diabetes mellitus for all indications.
WARNING: LACTIC ACIDOSIS WITH SYNJARDY AND SYNJARDY XR
Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Symptoms included malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Laboratory abnormalities included elevated blood lactate levels, anion gap acidosis, increased lactate/pyruvate ratio, and metformin plasma levels generally >5 mcg/mL.
Risk factors include renal impairment, concomitant use of certain drugs, age ≥65 years old, radiological studies with contrast, surgery and other procedures, hypoxic states, excessive alcohol intake, and hepatic impairment. Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided in the full Prescribing Information.
If lactic acidosis is suspected, discontinue SYNJARDY or SYNJARDY XR and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.
CONTRAINDICATIONS
JARDIANCE: Hypersensitivity to empagliflozin or any of the excipients in JARDIANCE, reactions such as angioedema have occurred.
SYNJARDY and SYNJARDY XR: Severe renal impairment (eGFR 30 mL/min/1.73 m2), end-stage renal disease, or dialysis; acute or chronic metabolic acidosis, including diabetic ketoacidosis; hypersensitivity to empagliflozin, metformin, or any of the excipients in SYNJARDY or SYNJARDY XR, reactions such as angioedema have occurred.
WARNINGS AND PRECAUTIONS
Lactic Acidosis: SYNJARDY, SYNJARDY XR
There have been cases of metformin-associated lactic acidosis, including fatal cases. These cases had a subtle onset and were accompanied by nonspecific symptoms such as malaise, myalgias, abdominal pain, respiratory distress, or increased somnolence; however, hypothermia, hypotension, and resistant bradyarrhythmias have occurred with severe acidosis. Additional findings included elevated blood lactate concentrations (>5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), and an increased lactate: pyruvate ratio, metformin plasma levels generally >5 mcg/mL.
If lactic acidosis is suspected, immediately discontinue SYNJARDY or SYNJARDY XR and institute general supportive measures promptly in a hospital setting. Prompt hemodialysis is recommended to correct the acidosis.
Educate patients and their families about the symptoms of lactic acidosis and, if these symptoms occur, instruct them to discontinue SYNJARDY or SYNJARDY XR and promptly notify their healthcare provider.
Recommendations to reduce the risk include:
- Renal Impairment: Obtain eGFR prior to initiating and annually, or more frequently, in patients at increased risk of developing renal impairment
- Drug Interactions: More frequent monitoring is recommended when administered with drugs that impair renal function, result in hemodynamic change, interfere with acid-base balance, or increase metformin accumulation
- Age 65 or Greater: Assess renal function more frequently
- Radiological Studies with Contrast: Stop SYNJARDY or SYNJARDY XR at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR of <60 mL/min/1.73 m2; patients with a history of hepatic impairment, alcoholism or heart failure; or patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the procedure and restart SYNJARDY or SYNJARDY XR if renal function is stable
- Surgery and Other Procedures: Discontinue while patients have restricted food and fluid intake
- Hypoxic States: Discontinue in conditions associated with hypoxemia
- Excessive Alcohol Intake: Warn patients against excessive alcohol intake
- Hepatic Impairment: Avoid use in patients with hepatic disease
Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis: JARDIANCE, SYNJARDY, SYNJARDY XR Empagliflozin increases the risk of life-threatening ketoacidosis in patients with type 1 diabetes and fatal ketoacidosis has occurred with empagliflozin. Type 2 diabetes and pancreatic disorders are also risk factors for ketoacidosis and fatal events of ketoacidosis have been reported in patients with type 2 diabetes using JARDIANCE, SYNJARDY, or SYNJARDY XR. Precipitating conditions for diabetic ketoacidosis or other ketoacidosis include under-insulinization due to insulin dose reduction or missed insulin doses, acute febrile illness, reduced caloric intake, ketogenic diet, surgery, volume depletion, and alcohol abuse. Signs and symptoms of diabetic ketoacidosis are consistent with dehydration and severe metabolic acidosis and include nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath. Assess patients who present with signs and symptoms of metabolic ketoacidosis, regardless of blood glucose levels. If suspected, discontinue JARDIANCE, SYNJARDY, or SYNJARDY XR, treat promptly and monitor for resolution before restarting. Consider ketone monitoring in patients with type 1 diabetes mellitus as well as in others at risk for ketoacidosis. Withhold JARDIANCE, SYNJARDY, or SYNJARDY XR in clinical situations known to predispose to ketoacidosis and resume when clinically stable. Educate all patients on the signs and symptoms of ketoacidosis and instruct patients to discontinue JARDIANCE, SYNJARDY, or SYNJARDY XR and seek medical attention immediately if signs and symptoms occur.
Volume Depletion: JARDIANCE, SYNJARDY, SYNJARDY XR
Empagliflozin can cause intravascular volume depletion which may manifest as symptomatic hypotension or acute transient changes in creatinine. Acute kidney injury requiring hospitalization and dialysis has been reported in patients with type 2 diabetes receiving SGLT2 inhibitors, including empagliflozin. Before initiating, assess volume status and renal function in patients with impaired renal function (eGFR <60 mL/min/1.73 m2), elderly patients or patients on loop diuretics. In patients with volume depletion, correct this condition before initiating JARDIANCE, SYNJARDY, or SYNJARDY XR. After initiating, monitor for signs and symptoms of volume depletion and renal function.
Urosepsis and Pyelonephritis: JARDIANCE, SYNJARDY, SYNJARDY XR
Serious urinary tract infections, including urosepsis and pyelonephritis, requiring hospitalization have been identified in patients receiving empagliflozin. Treatment with empagliflozin increases the risk of urinary tract infections. Evaluate for signs and symptoms of urinary tract infections and treat promptly.
Hypoglycemia: JARDIANCE, SYNJARDY, SYNJARDY XR
In adults, the use of JARDIANCE, SYNJARDY or SYNJARDY XR in combination with insulin or insulin secretagogues can increase the risk of hypoglycemia. In pediatric patients aged 10 years and older (JARDIANCE and SYNJARDY), the risk of hypoglycemia was higher with empagliflozin regardless of insulin use. The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly administered insulin secretagogues) or insulin.
Lower Limb Amputation: JARDIANCE, SYNJARDY, SYNJARDY XR
Lower limb amputations have been observed in patients with chronic kidney disease taking JARDIANCE. SYNJARDY and SYNJARDY XR are not indicated for the treatment of chronic kidney disease. Peripheral artery disease, and diabetic foot infection (including osteomyelitis), were the most common precipitating medical events leading to the need for an amputation. The risk of amputation was highest in patients with a baseline history of diabetic foot, peripheral artery disease (including previous amputation) or diabetes. Counsel patients receiving JARDIANCE, SYNJARDY, or SYNJARDY XR about the importance of routine preventative foot care and monitor for signs and symptoms of diabetic foot infection (including osteomyelitis), new pain or tenderness, sores or ulcers involving the lower limbs, and institute appropriate treatment.
Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene): JARDIANCE, SYNJARDY, SYNJARDY XR
Serious, life-threatening cases requiring urgent surgical intervention have occurred in both females and males. Serious outcomes have included hospitalization, multiple surgeries, and death. Assess patients presenting with pain or tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise. If suspected, institute prompt treatment and discontinue JARDIANCE, SYNJARDY or SYNJARDY XR.
Genital Mycotic Infections: JARDIANCE, SYNJARDY, SYNJARDY XR
Empagliflozin increases the risk of genital mycotic infections, especially in patients with prior infections. Monitor and treat as appropriate.
Hypersensitivity Reactions: JARDIANCE, SYNJARDY, SYNJARDY XR
Serious hypersensitivity reactions have occurred with empagliflozin (angioedema). If hypersensitivity reactions occur, discontinue JARDIANCE, SYNJARDY or SYNJARDY XR, treat promptly, and monitor until signs and symptoms resolve.
Vitamin B12 Deficiency: SYNJARDY, SYNJARDY XR
Metformin may lower vitamin B12 levels. Measure hematologic parameters annually and vitamin B12 at 2- to 3-year intervals and manage any abnormalities.
MOST COMMON ADVERSE REACTIONS (≥5%)
JARDIANCE: urinary tract infections and female genital mycotic infections.
SYNJARDY and SYNJARDY XR: urinary tract infections and female genital mycotic infections, diarrhea, nausea/vomiting, flatulence, abdominal discomfort, indigestion, asthenia, and headache.
DRUG INTERACTIONS
Carbonic Anhydrase Inhibitors: The concomitant use of carbonic anhydrase inhibitors (e.g., topiramate) and metformin may increase the risk of lactic acidosis. Consider more frequent monitoring.
Drugs that reduce metformin clearance such as ranolazine, vandetanib, dolutegravir, or cimetidine may increase the accumulation of metformin and increase the risk of lactic acidosis. Consider the benefits and risks of concomitant use.
Alcohol: Alcohol is known to potentiate the effect of metformin on lactate metabolism. Warn patients against excessive alcohol intake while taking SYNJARDY or SYNJARDY XR.
Diuretics: Coadministration of empagliflozin with diuretics may enhance the potential for volume depletion. Monitor for signs and symptoms.
Lithium: Concomitant use of empagliflozin with lithium may decrease serum lithium concentrations. Monitor more frequently during JARDIANCE, SYNJARDY or SYNJARDY XR initiation and dosage changes.
USE IN SPECIAL POPULATIONS
Pregnancy: JARDIANCE, SYNJARDY, and SYNJARDY XR are not recommended during the second and third trimesters. With SYNJARDY or SYNJARDY XR, discuss the potential for unintended pregnancy with premenopausal women as therapy with metformin may result in ovulation in some anovulatory women.
Lactation: JARDIANCE, SYNJARDY, and SYNJARDY XR are not recommended while breastfeeding.
Geriatric Use: Empagliflozin is expected to have diminished glycemic efficacy in elderly patients with renal impairment. Assess renal function more frequently in elderly patients. For SYNJARDY and SYNJARDY XR, dose selection should be cautious, starting at the lowest dose. The incidence of volume depletion-related adverse reactions and urinary tract infections increased in T2D patients ≥75 years treated with empagliflozin.
CL-JAR-100189 10.30.2023
Please see SYNJARDY Prescribing Information, including Boxed Warning and Medication Guide.
Please see SYNJARDY XR Prescribing Information, including Boxed Warning and Medication Guide.
Please see JARDIANCE Prescribing Information and Medication Guide.
References
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Zinman B, Wanner C, Lachin JM, et al; the EMPA-REG OUTCOME Trial Investigators. N Engl J Med. 2015; 373(22):2117-2128.
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Data on file. Boehringer Ingelheim Pharmaceuticals, Inc.