Jardiance Drug Information
Generic name: EMPAGLIFLOZIN
Sodium-Glucose Cotransporter 2 Inhibitor [EPC]
Uses of Jardiance
- JARDIANCE is indicated: to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure. to reduce the risk of cardiovascular death in adults with type 2 diabetes mellitus and established cardiovascular disease. as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. JARDIANCE is a sodium-glucose co-transporter 2 (SGLT2) inhibitor indicated: To reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure.
- Limitations of Use: Not recommended in patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients. JARDIANCE is not recommended for use to improve glycemic control in adults with type 2 diabetes mellitus with an eGFR less than 30 mL/min/1.73 m 2. JARDIANCE is likely to be ineffective in this setting based upon its mechanism of action.
Dosage & Administration of Jardiance
Prior to Initiation of JARDIANCE
Assess renal function before initiating JARDIANCE and as clinically indicated. In patients with volume depletion, correct this condition before initiating JARDIANCE.
Recommended Dosage
The recommended dose of JARDIANCE is 10 mg once daily in the morning, taken with or without food. For additional glycemic control, the dose may be increased to 25 mg in patients tolerating JARDIANCE. Use for glycemic control is not recommended in patients with an eGFR less than 30 mL/min/1.73 m 2.
Data are insufficient to provide a dosing recommendation in patients; who have type 2 diabetes and established cardiovascular disease with an eGFR less than 30 mL/min/1.73 m 2, or who have heart failure with an eGFR less than 20 mL/min/1.73 m 2. JARDIANCE is contraindicated in patients on dialysis.
Side Effects of Jardiance
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. JARDIANCE has been evaluated in clinical trials in patients with type 2 diabetes mellitus and in patients with heart failure. The overall safety profile of JARDIANCE was generally consistent across the studied indications.
Clinical Trials in Patients with Type 2 Diabetes Mellitus The data in Table 1 are derived from a pool of four 24-week placebo-controlled trials and 18-week data from a placebo-controlled trial with insulin in patients with type 2 diabetes. JARDIANCE was used as monotherapy in one trial and as add-on therapy in four trials. These data reflect exposure of 1976 patients to JARDIANCE with a mean exposure duration of approximately 23 weeks.
Patients received placebo (N=995), JARDIANCE 10 mg (N=999), or JARDIANCE 25 mg (N=977) once daily. The mean age of the population was 56 years and 3% were older than 75 years of age. At baseline, 57% of the population had diabetes more than 5 years and had a mean hemoglobin A1c (HbA1c) of 8%.
Established microvascular complications of diabetes at baseline included diabetic nephropathy (7%), retinopathy (8%), or neuropathy (16%). Table 1 shows common adverse reactions (excluding hypoglycemia) associated with the use of JARDIANCE. The adverse reactions were not present at baseline, occurred more commonly on JARDIANCE than on placebo and occurred in greater than or equal to 2% of patients treated with JARDIANCE 10 mg or JARDIANCE 25 mg.
Volume Depletion JARDIANCE causes an osmotic diuresis, which may lead to intravascular volume contraction and adverse reactions related to volume depletion. In the pool of five placebo-controlled clinical trials, adverse reactions related to volume depletion (e.g., blood pressure (ambulatory) decreased, blood pressure systolic decreased, dehydration, hypotension, hypovolemia, orthostatic hypotension, and syncope) were reported by 0.3%, 0.5%, and 0.3% of patients treated with placebo, JARDIANCE 10 mg, and JARDIANCE 25 mg, respectively. JARDIANCE may increase the risk of hypotension in patients at risk for volume contraction.
Increased Urination In the pool of five placebo-controlled clinical trials, adverse reactions of increased urination (e.g., polyuria, pollakiuria, and nocturia) occurred more frequently on JARDIANCE than on placebo (see Table 1 ). Hypoglycemia The incidence of hypoglycemia by study is shown in Table 2. The incidence of hypoglycemia increased when JARDIANCE was administered with insulin or sulfonylurea.
Table 2 Incidence of Overall a and Severe b Hypoglycemic Events in Placebo-Controlled Clinical Studies c Genital Mycotic Infections In the pool of five placebo-controlled clinical trials, the incidence of genital mycotic infections (e.g., vaginal mycotic infection, vaginal infection, genital infection fungal, vulvovaginal candidiasis, and vulvitis) was increased in patients treated with JARDIANCE compared to placebo, occurring in 0.9%, 4.1%, and 3.7% of patients randomized to placebo, JARDIANCE 10 mg, and JARDIANCE 25 mg, respectively. Genital mycotic infections occurred more frequently in female than male patients (see Table 1 ). Urinary Tract Infections In the pool of five placebo-controlled clinical trials, the incidence of urinary tract infections (e.g., urinary tract infection, asymptomatic bacteriuria, and cystitis) was increased in patients treated with JARDIANCE compared to placebo (see Table 1 ).
Patients with a history of chronic or recurrent urinary tract infections were more likely to experience a urinary tract infection. Urinary tract infections occurred more frequently in female patients. In both studies, patients were randomized to JARDIANCE 10 mg or placebo.
The safety profile in patients with heart failure was generally consistent with that observed in patients with type 2 diabetes mellitus. Laboratory Tests Increases in Serum Creatinine and Decreases in eGFR Initiation of JARDIANCE causes an increase in serum creatinine and decrease in eGFR within weeks of starting therapy and then these changes stabilize. In a study of patients with moderate renal impairment, larger mean changes were observed.
In a long-term cardiovascular outcomes trial, the increase in serum creatinine and decrease in eGFR generally did not exceed 0.1 mg/dL and -9.0 mL/min/1.73 m 2, respectively, at Week 4, and reversed after treatment discontinuation, suggesting acute hemodynamic changes may play a role in the renal function changes observed with JARDIANCE. Increase in Low-Density Lipoprotein Cholesterol (LDL-C) Dose-related increases in low-density lipoprotein cholesterol (LDL-C) were observed in patients treated with JARDIANCE. The range of mean baseline LDL-C levels was 90.3 to 90.6 mg/dL across treatment groups.
At the end of treatment, 0.6%, 2.7%, and 3.5% of patients with hematocrits initially within the reference range had values above the upper limit of the reference range with placebo, JARDIANCE 10 mg, and JARDIANCE 25 mg, respectively.
Postmarketing Experience
Additional adverse reactions have been identified during postapproval use of JARDIANCE. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Gastrointestinal Disorders: Constipation Infections: Necrotizing fasciitis of the perineum (Fournier's gangrene), urosepsis and pyelonephritis Metabolism and Nutrition Disorders: Ketoacidosis Renal and Urinary Disorders: Acute kidney injury Skin and Subcutaneous Tissue Disorders: Angioedema, skin reactions (e.g., rash, urticaria)
| Adverse Reactions | Placebo (%) N=995 | JARDIANCE 10 mg (%) N=999 | JARDIANCE 25 mg (%) N=977 |
|---|---|---|---|
| a Predefined adverse event grouping, including, but not limited to, urinary tract infection, asymptomatic bacteriuria, cystitis b Female genital mycotic infections include the following adverse reactions: vulvovaginal mycotic infection, vaginal infection, vulvitis, vulvovaginal candidiasis, genital infection, genital candidiasis, genital infection fungal, genitourinary tract infection, vulvovaginitis, cervicitis, urogenital infection fungal, vaginitis bacterial. Percentages calculated with the number of female subjects in each group as denominator: placebo (N=481), JARDIANCE 10 mg (N=443), JARDIANCE 25 mg (N=420). c Predefined adverse event grouping, including, but not limited to, polyuria, pollakiuria, and nocturia d Male genital mycotic infections include the following adverse reactions: balanoposthitis, balanitis, genital infections fungal, genitourinary tract infection, balanitis candida, scrotal abscess, penile infection. Percentages calculated with the number of male subjects in each group as denominator: placebo (N=514), JARDIANCE 10 mg (N=556), JARDIANCE 25 mg (N=557). | |||
| Urinary tract infection a | 7.6 | 9.3 | 7.6 |
| Female genital mycotic infections b | 1.5 | 5.4 | 6.4 |
| Upper respiratory tract infection | 3.8 | 3.1 | 4.0 |
| Increased urination c | 1.0 | 3.4 | 3.2 |
| Dyslipidemia | 3.4 | 3.9 | 2.9 |
| Arthralgia | 2.2 | 2.4 | 2.3 |
| Male genital mycotic infections d | 0.4 | 3.1 | 1.6 |
| Nausea | 1.4 | 2.3 | 1.1 |
| a Overall hypoglycemic events: plasma or capillary glucose of less than or equal to 70 mg/dL b Severe hypoglycemic events: requiring assistance regardless of blood glucose c Treated set (patients who had received at least one dose of study drug) d Insulin dose could not be adjusted during the initial 18-week treatment period | |||
| Monotherapy (24 weeks) | Placebo (n=229) | JARDIANCE 10 mg (n=224) | JARDIANCE 25 mg (n=223) |
| Overall (%) | 0.4 | 0.4 | 0.4 |
| Severe (%) | 0 | 0 | 0 |
| In Combination with Metformin (24 weeks) | Placebo + Metformin (n=206) | JARDIANCE 10 mg + Metformin (n=217) | JARDIANCE 25 mg + Metformin (n=214) |
| Overall (%) | 0.5 | 1.8 | 1.4 |
| Severe (%) | 0 | 0 | 0 |
| In Combination with Metformin + Sulfonylurea (24 weeks) | Placebo (n=225) | JARDIANCE 10 mg + Metformin + Sulfonylurea (n=224) | JARDIANCE 25 mg + Metformin + Sulfonylurea (n=217) |
| Overall (%) | 8.4 | 16.1 | 11.5 |
| Severe (%) | 0 | 0 | 0 |
| In Combination with Pioglitazone +/- Metformin (24 weeks) | Placebo (n=165) | JARDIANCE 10 mg + Pioglitazone +/- Metformin (n=165) | JARDIANCE 25 mg + Pioglitazone +/- Metformin (n=168) |
| Overall (%) | 1.8 | 1.2 | 2.4 |
| Severe (%) | 0 | 0 | 0 |
| In Combination with Basal Insulin +/- Metformin (18 weeks d ) | Placebo (n=170) | JARDIANCE 10 mg (n=169) | JARDIANCE 25 mg (n=155) |
| Overall (%) | 20.6 | 19.5 | 28.4 |
| Severe (%) | 0 | 0 | 1.3 |
| In Combination with MDI Insulin +/-Metformin (18 weeks d ) | Placebo (n=188) | JARDIANCE 10 mg (n=186) | JARDIANCE 25 mg (n=189) |
| Overall (%) | 37.2 | 39.8 | 41.3 |
| Severe (%) | 0.5 | 0.5 | 0.5 |
Warnings & Cautions for Jardiance
Ketoacidosis Reports of ketoacidosis, a serious life-threatening condition requiring urgent hospitalization have been identified in clinical trials and postmarketing surveillance in patients with type 1 and type 2 diabetes mellitus receiving sodium glucose co-transporter-2 (SGLT2) inhibitors, including JARDIANCE. Fatal cases of ketoacidosis have been reported in patients taking JARDIANCE. In placebo-controlled trials of patients with type 1 diabetes, the risk of ketoacidosis was increased in patients who received SGLT2 inhibitors compared to patients who received placebo.
JARDIANCE is not indicated for the treatment of patients with type 1 diabetes mellitus. Patients treated with JARDIANCE who present with signs and symptoms consistent with severe metabolic acidosis should be assessed for ketoacidosis regardless of presenting blood glucose levels, as ketoacidosis associated with JARDIANCE may be present even if blood glucose levels are less than 250 mg/dL. If ketoacidosis is suspected, JARDIANCE should be discontinued, patient should be evaluated, and prompt treatment should be instituted.
Treatment of ketoacidosis may require insulin, fluid and carbohydrate replacement. In many of the postmarketing reports, and particularly in patients with type 1 diabetes, the presence of ketoacidosis was not immediately recognized and institution of treatment was delayed because presenting blood glucose levels were below those typically expected for diabetic ketoacidosis (often less than 250 mg/dL). Signs and symptoms at presentation were consistent with dehydration and severe metabolic acidosis and included nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath.
In some but not all cases, factors predisposing to ketoacidosis such as insulin dose reduction, acute febrile illness, reduced caloric intake, surgery, pancreatic disorders suggesting insulin deficiency (e.g., type 1 diabetes, history of pancreatitis or pancreatic surgery), and alcohol abuse were identified. Before initiating JARDIANCE, consider factors in the patient history that may predispose to ketoacidosis including pancreatic insulin deficiency from any cause, caloric restriction, and alcohol abuse. For patients who undergo scheduled surgery, consider temporarily discontinuing JARDIANCE for at least 3 days prior to surgery.
Consider monitoring for ketoacidosis and temporarily discontinuing JARDIANCE in other clinical situations known to predispose to ketoacidosis (e.g., prolonged fasting due to acute illness or post-surgery). Ensure risk factors for ketoacidosis are resolved prior to restarting JARDIANCE. Educate patients on the signs and symptoms of ketoacidosis and instruct patients to discontinue JARDIANCE and seek medical attention immediately if signs and symptoms occur.
Volume Depletion JARDIANCE can cause intravascular volume depletion which may sometimes manifest as symptomatic hypotension or acute transient changes in creatinine. There have been post-marketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients with type 2 diabetes mellitus receiving SGLT2 inhibitors, including JARDIANCE. Patients with impaired renal function (eGFR less than 60 mL/min/1.73 m 2 ), elderly patients, or patients on loop diuretics may be at increased risk for volume depletion or hypotension.
Before initiating JARDIANCE in patients with one or more of these characteristics, assess volume status and renal function. In patients with volume depletion, correct this condition before initiating JARDIANCE. Monitor for signs and symptoms of volume depletion, and renal function after initiating therapy.
Urosepsis and Pyelonephritis There have been reports of serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization in patients receiving SGLT2 inhibitors, including JARDIANCE. Treatment with SGLT2 inhibitors increases the risk for urinary tract infections. Evaluate patients for signs and symptoms of urinary tract infections and treat promptly, if indicated.
Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues Insulin and insulin secretagogues are known to cause hypoglycemia. The risk of hypoglycemia is increased when JARDIANCE is used in combination with insulin secretagogues (e.g., sulfonylurea) or insulin. Therefore, a lower dose of the insulin secretagogue or insulin may be required to reduce the risk of hypoglycemia when used in combination with JARDIANCE.
Necrotizing Fasciitis of the Perineum (Fournier's Gangrene) Reports of necrotizing fasciitis of the perineum (Fournier's gangrene), a rare but serious and life-threatening necrotizing infection requiring urgent surgical intervention, have been identified in patients with diabetes mellitus receiving SGLT2 inhibitors, including JARDIANCE. Cases have been reported in both females and males. Serious outcomes have included hospitalization, multiple surgeries, and death.
Patients treated with JARDIANCE presenting with pain or tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise, should be assessed for necrotizing fasciitis. If suspected, start treatment immediately with broad-spectrum antibiotics and, if necessary, surgical debridement. Discontinue JARDIANCE, closely monitor blood glucose levels, and provide appropriate alternative therapy for glycemic control.
Genital Mycotic Infections
JARDIANCE increases the risk for genital mycotic infections. Patients with a history of chronic or recurrent genital mycotic infections were more likely to develop genital mycotic infections. Monitor and treat as appropriate.
Hypersensitivity Reactions There have been postmarketing reports of serious hypersensitivity reactions (e.g., angioedema) in patients treated with JARDIANCE. If a hypersensitivity reaction occurs, discontinue JARDIANCE; treat promptly per standard of care, and monitor until signs and symptoms resolve. JARDIANCE is contraindicated in patients with hypersensitivity to empagliflozin or any of the excipients in JARDIANCE.
Drug Interactions with Jardiance
Table 3 Clinically Relevant Interactions with JARDIANCE See full prescribing information for information on drug interactions and interference of JARDIANCE with laboratory tests.
| Diuretics | |
|---|---|
| Clinical Impact | Coadministration of empagliflozin with diuretics resulted in increased urine volume and frequency of voids, which might enhance the potential for volume depletion. |
| Intervention | Before initiating JARDIANCE, assess volume status and renal function. In patients with volume depletion, correct this condition before initiating JARDIANCE. Monitor for signs and symptoms of volume depletion, and renal function after initiating therapy. |
| Insulin or Insulin Secretagogues | |
| Clinical Impact | The risk of hypoglycemia is increased when JARDIANCE is used in combination with insulin secretagogues (e.g., sulfonylurea) or insulin. |
| Intervention | Coadministration of JARDIANCE with an insulin secretagogue (e.g., sulfonylurea) or insulin may require lower doses of the insulin secretagogue or insulin to reduce the risk of hypoglycemia. |
| Lithium | |
| Clinical Impact | Concomitant use of an SGLT2 inhibitor with lithium may decrease serum lithium concentrations. |
| Intervention | Monitor serum lithium concentration more frequently during JARDIANCE initiation and dosage changes. |
| Positive Urine Glucose Test | |
| Clinical Impact | SGLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests. |
| Intervention | Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors. Use alternative methods to monitor glycemic control. |
| Interference with 1,5-anhydroglucitol (1,5-AG) Assay | |
| Clinical Impact | Measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors. |
| Intervention | Monitoring glycemic control with 1,5-AG assay is not recommended. Use alternative methods to monitor glycemic control. |
Pregnancy Safety for Jardiance
Pregnancy Risk Summary Based on animal data showing adverse renal effects, JARDIANCE is not recommended during the second and third trimesters of pregnancy. The limited available data with JARDIANCE in pregnant women are not sufficient to determine a drug-associated risk for major birth defects and miscarriage. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy.
In animal studies, adverse renal changes were observed in rats when empagliflozin was administered during a period of renal development corresponding to the late second and third trimesters of human pregnancy. Doses approximately 13-times the maximum clinical dose caused renal pelvic and tubule dilatations that were reversible. The estimated background risk of miscarriage for the indicated population is unknown.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk: Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity.
Data Animal Data Empagliflozin dosed directly to juvenile rats from postnatal day (PND) 21 until PND 90 at doses of mg/kg/day caused increased kidney weights and renal tubular and pelvic dilatation at 100 mg/kg/day, which approximates 13-times the maximum clinical dose of 25 mg, based on AUC. These findings were not observed after a 13-week, drug-free recovery period. These outcomes occurred with drug exposure during periods of renal development in rats that correspond to the late second and third trimester of human renal development.
In embryo-fetal development studies in rats and rabbits, empagliflozin was administered for intervals coinciding with the first trimester period of organogenesis in humans. Doses up to 300 mg/kg/day, which approximates 48-times (rats) and 128-times (rabbits) the maximum clinical dose of 25 mg (based on AUC), did not result in adverse developmental effects. In rats, at higher doses of empagliflozin causing maternal toxicity, malformations of limb bones increased in fetuses at 700 mg/kg/day or 154-times the 25 mg maximum clinical dose.
Empagliflozin crosses the placenta and reaches fetal tissues in rats. In the rabbit, higher doses of empagliflozin resulted in maternal and fetal toxicity at 700 mg/kg/day, or 139-times the 25 mg maximum clinical dose. In pre- and postnatal development studies in pregnant rats, empagliflozin was administered from gestation day 6 through to lactation day 20 (weaning) at up to 100 mg/kg/day (approximately 16-times the 25 mg maximum clinical dose) without maternal toxicity.
Reduced body weight was observed in the offspring at greater than or equal to 30 mg/kg/day (approximately 4-times the 25 mg maximum clinical dose).
Pediatric Use of Jardiance
Pediatric Use The safety and effectiveness of JARDIANCE have not been established in pediatric patients.
Contraindications for Jardiance
Hypersensitivity to empagliflozin or any of the excipients in JARDIANCE, reactions such as angioedema have occurred. Patients on dialysis. Hypersensitivity to empagliflozin or any of the excipients in JARDIANCE Patients on dialysis
Overdosage Information for Jardiance
In the event of an overdose with JARDIANCE, contact the Poison Control Center. Removal of empagliflozin by hemodialysis has not been studied.
Clinical Studies of Jardiance
Glycemic Control in Patients with Type 2 Diabetes Mellitus JARDIANCE has been studied as monotherapy and in combination with metformin, sulfonylurea, pioglitazone, linagliptin, and insulin. JARDIANCE has also been studied in patients with type 2 diabetes with mild or moderate renal impairment. In patients with type 2 diabetes, treatment with JARDIANCE reduced hemoglobin A1c (HbA1c), compared to placebo.
The reduction in HbA1c for JARDIANCE compared with placebo was observed across subgroups including gender, race, geographic region, baseline BMI and duration of disease. Monotherapy A total of 986 patients with type 2 diabetes participated in a double-blind, placebo-controlled study to evaluate the efficacy and safety of JARDIANCE monotherapy. 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 an HbA1c between 7% and 10% were randomized to placebo, JARDIANCE 10 mg, JARDIANCE 25 mg, or a reference comparator. Table 4 Results at Week 24 From a Placebo-Controlled Monotherapy Study of JARDIANCE Change at Each Time Point (Completers) and at Week 24 (mITT Population) - LOCF At Week 24, the systolic blood pressure was statistically significantly reduced compared to placebo by -2.6 mmHg (placebo-adjusted, p-value=0.0231) in patients randomized to 10 mg of JARDIANCE and by -3.4 mmHg (placebo-corrected, p-value=0.0028) in patients randomized to 25 mg of JARDIANCE. Patients with type 2 diabetes inadequately controlled on at least 1500 mg of metformin per day entered an open-label 2-week placebo run-in.
Initial Combination Therapy with Metformin A total of 1364 patients with type 2 diabetes participated in a double-blind, randomized, active-controlled study to evaluate the efficacy and safety of JARDIANCE in combination with metformin as initial therapy compared to the corresponding individual components. At Week 24, initial therapy of JARDIANCE in combination with metformin provided statistically significant reductions in HbA1c (p-value <0.01) compared to the individual components (see Table 6 ). Patients with type 2 diabetes inadequately controlled on at least 1500 mg of metformin per day entered a single-blind placebo run-in period for 2 weeks.
There was no statistically significant difference in body weight compared to JARDIANCE alone. Active-Controlled Study versus Glimepiride in Combination with Metformin The efficacy of JARDIANCE was evaluated in a double-blind, glimepiride-controlled, study in 1545 patients with type 2 diabetes with insufficient glycemic control despite metformin therapy. Patients with inadequate glycemic control and an HbA1c between 7% and 10% after a 2-week run-in period were randomized to glimepiride or JARDIANCE 25 mg.
The difference in observed effect size between JARDIANCE 25 mg and glimepiride excluded the pre-specified non-inferiority margin of 0.3%. The mean daily dose of glimepiride was 2.7 mg and the maximal approved dose in the United States is 8 mg per day. Table 8 Results at Week 52 from an Active-Controlled Study Comparing JARDIANCE to Glimepiride as Add-On Therapy in Patients Inadequately Controlled on Metformin Change at Each Time Point (Completers) and at Week 52 (mITT Population) - LOCF At Week 52, the adjusted mean change from baseline in systolic blood pressure was -3.6 mmHg, compared to 2.2 mmHg for glimepiride.
The differences between treatment groups for systolic blood pressure was statistically significant (p-value <0.0001). The Week 104 analysis included data with and without concomitant glycemic rescue medication, as well as off-treatment data. Missing data for patients not providing any information at the visit were imputed based on the observed off-treatment data.
In this multiple imputation analysis, 13.9% of the data were imputed for JARDIANCE 25 mg and 12.9% for glimepiride. Table 9 Results of Placebo-Controlled Study for JARDIANCE in Combination Therapy with Pioglitazone Add-On Combination with Insulin with or without Metformin and/or Sulfonylureas A total of 494 patients with type 2 diabetes inadequately controlled on insulin, or insulin in combination with oral drugs participated in a double-blind, placebo-controlled study to evaluate the efficacy of JARDIANCE as add-on therapy to insulin over 78 weeks. Patients entered a 2-week placebo run-in period on basal insulin (e.g., insulin glargine, insulin detemir, or NPH insulin) with or without metformin and/or sulfonylurea background therapy.
Following the run-in period, patients with inadequate glycemic control were randomized to the addition of JARDIANCE 10 mg, JARDIANCE 25 mg, or placebo. Patients were maintained on a stable dose of insulin prior to enrollment, during the run-in period, and during the first 18 weeks of treatment. For the remaining 60 weeks, insulin could be adjusted.
JARDIANCE used in combination with insulin (with or without metformin and/or sulfonylurea) provided statistically significant reductions in HbA1c and FPG compared to placebo after both 18 and 78 weeks of treatment (see Table 10 ). JARDIANCE 10 mg or 25 mg daily also resulted in statistically significantly greater percent body weight reduction compared to placebo. Table 10 Results at Week 18 and 78 for a Placebo-Controlled Study for JARDIANCE in Combination with Insulin Add-on Combination with MDI Insulin with or without Metformin A total of 563 patients with type 2 diabetes inadequately controlled on multiple daily injections (MDI) of insulin (total daily dose >60 IU), alone or in combination with metformin, participated in a double-blind, placebo-controlled study to evaluate the efficacy of JARDIANCE as add-on therapy to MDI insulin over 18 weeks.
JARDIANCE 10 mg or 25 mg daily used in combination with MDI insulin (with or without metformin) provided statistically significant reductions in HbA1c compared to placebo after 18 weeks of treatment (see Table 11 ). Table 11 Results at Week 18 for a Placebo-Controlled Study for JARDIANCE in Combination with Insulin and with or without Metformin During an extension period with treatment for up to 52 weeks, insulin could be adjusted to achieve defined glucose target levels. At Week 24, JARDIANCE 25 mg provided statistically significant reduction in HbA1c relative to placebo in patients with mild to moderate renal impairment (see Table 12 ).
A statistically significant reduction relative to placebo was also observed with JARDIANCE 25 mg in patients with either mild or moderate renal impairment and with JARDIANCE 10 mg in patients with mild renal impairment. The glucose lowering efficacy of JARDIANCE 25 mg decreased with decreasing level of renal function in the mild to moderate range. Table 12 Results at Week 24 (LOCF) of Placebo-Controlled Study for JARDIANCE in Patients with Type 2 Diabetes and Renal Impairment For patients with severe renal impairment, the analyses of changes in HbA1c and FPG showed no discernible treatment effect of JARDIANCE 25 mg compared to placebo.
Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus and Atherosclerotic Cardiovascular Disease The effect of JARDIANCE on cardiovascular risk in adult patients with type 2 diabetes and established, stable, atherosclerotic cardiovascular disease was evaluated in the EMPA-REG OUTCOME study, a multicenter, multinational, randomized, double-blind parallel group trial. The study compared the risk of experiencing a major adverse cardiovascular event (MACE) between JARDIANCE and placebo when these were added to and used concomitantly with standard of care treatments for diabetes and atherosclerotic cardiovascular disease. Coadministered antidiabetic medications were to be kept stable for the first 12 weeks of the trial.
Thereafter, antidiabetic and atherosclerotic therapies could be adjusted, at the discretion of investigators, to ensure participants were treated according to the standard care for these diseases. Approximately 72% of the study population was Caucasian, 22% was Asian, and 5% was Black. The mean age was 63 years and approximately 72% were male.
All patients in the study had inadequately controlled type 2 diabetes mellitus at baseline (HbA1c greater than or equal to 7%). The mean HbA1c at baseline was 8.1% and 57% of participants had diabetes for more than 10 years. At baseline, the mean systolic blood pressure was 136 mmHg, the mean diastolic blood pressure was 76 mmHg, the mean LDL was 86 mg/dL, the mean HDL was 44 mg/dL, and the mean urinary albumin to creatinine ratio (UACR) was 175 mg/g.
The primary endpoint in EMPA-REG OUTCOME was the time to first occurrence of a Major Adverse Cardiac Event (MACE). A major adverse cardiac event was defined as occurrence of either a cardiovascular death or a non-fatal myocardial infarction (MI) or a non-fatal stroke. The statistical analysis plan had pre-specified that the 10 and 25 mg doses would be combined.
A Cox proportional hazards model was used to test for non-inferiority against the pre-specified risk margin of 1.3 for the hazard ratio of MACE and superiority on MACE if non-inferiority was demonstrated. Type-1 error was controlled across multiples tests using a hierarchical testing strategy. JARDIANCE significantly reduced the risk of first occurrence of primary composite endpoint of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke HR: The treatment effect was due to a significant reduction in the risk of cardiovascular death in subjects randomized to empagliflozin HR: with no change in the risk of non-fatal myocardial infarction or non-fatal stroke (see Table 13 and Figures 5 and 6 ).
Results for the 10 mg and 25 mg empagliflozin doses were consistent with results for the combined dose groups. Table 13 Treatment Effect for the Primary Composite Endpoint and its Components a 2 Figure 5 Estimated Cumulative Incidence of First MACE Figure 6 Estimated Cumulative Incidence of Cardiovascular Death The efficacy of JARDIANCE on cardiovascular death was generally consistent across major demographic and disease subgroups. Vital status was obtained for 99.2% of subjects in the trial.
A total of 463 deaths were recorded during the EMPA-REG OUTCOME trial. Most of these deaths were categorized as cardiovascular deaths. The non-cardiovascular deaths were only a small proportion of deaths and were balanced between the treatment groups (2.1% in patients treated with JARDIANCE, and 2.4% of patients treated with placebo).
Figure 5 Figure 6 Heart Failure EMPEROR-Reduced (NCT03057977) was a double-blind study conducted in patients with chronic heart failure (New York Heart Association functional class II-IV) with left ventricular ejection fraction (LVEF) ≤40% to evaluate the efficacy and safety of JARDIANCE as adjunct to standard of care heart failure therapy. Approximately 71% of the study population were White, 18% Asian and 7% Black or African American. At baseline, 50% of the patients had type 2 diabetes mellitus.
At randomization, 75% of patients were NYHA class II, 24% were class III and 0.5% were class IV. The mean LVEF was 28%. At baseline, the mean eGFR was 62 mL/min/1.73 m 2 and the median urinary albumin to creatinine ratio (UACR) was 22 mg/g.
At baseline, 88% of patients were treated with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB), or angiotensin receptor-neprilysin inhibitors (ARNI), 95% with beta-blockers, 71% with mineralocorticoid receptor antagonists (MRA), and 95% with diuretics. The primary endpoint was the time to first event of either cardiovascular death (CV) or hospitalization for heart failure (HHF). First and recurrent HHF was assessed as a key secondary endpoint.
JARDIANCE was superior in reducing the risk of the primary composite endpoint of cardiovascular death or hospitalization for heart failure compared with placebo, mostly through a reduction in hospitalization for heart failure. JARDIANCE reduced the risk of first and recurrent HHF (see Table 14 and Figures 7 and 8 ). Table 14 Treatment Effect for the Primary Composite Endpoint, its Components, and Key Secondary Endpoints Figure 7 Time to First Occurrence of the Primary Composite Endpoint of Cardiovascular Death or Hospitalization for Heart Failure Figure 8 Time to Event of Hospitalization for Heart Failure (First and Recurrent) The results of the primary composite were generally consistent across the pre-specified subgroups (see Figure 9 ).
Figure 9 Treatment Effects for the Primary Composite Endpoint (Cardiovascular Death and Hospitalization for Heart Failure) Subgroup Analysis (EMPEROR-Reduced) LVEF >30%: Includes both above and below the median NT-proBNP. To be eligible for inclusion, patients with an LVEF >30% were required to meet a higher NT-proBNP threshold than those with LVEF ≤30%, unless they additionally had a history of HHF within the past 12 months. Approximately 76% of the study population were White, 14% Asian and 4% Black or African American.
At randomization, 82% of patients were NYHA class II, 18% were class III and 0.3% were class IV. JARDIANCE reduced the risk of first and recurrent HHF (see Table 15 and Figures 10 and 11 ).
| JARDIANCE 10 mg N=224 | JARDIANCE 25 mg N=224 | Placebo N=228 | |
|---|---|---|---|
| a Modified intent-to-treat population. Last observation on study (LOCF) was used to impute missing data at Week 24. At Week 24, 9.4%, 9.4%, and 30.7% was imputed for patients randomized to JARDIANCE 10 mg, JARDIANCE 25 mg, and placebo, respectively. b ANCOVA derived p-value <0.0001 (HbA1c: ANCOVA model includes baseline HbA1c, treatment, renal function, and region. Body weight and FPG: same model used as for HbA1c but additionally including baseline body weight/baseline FPG, respectively.) c FPG (mg/dL); for JARDIANCE 10 mg, n=223, for JARDIANCE 25 mg, n=223, and for placebo, n=226 | |||
| HbA1c (%) a | |||
| Baseline (mean) | 7.9 | 7.9 | 7.9 |
| Change from baseline (adjusted mean) | -0.7 | -0.8 | 0.1 |
| Difference from placebo (adjusted mean) (97.5% CI) | -0.7 b (-0.9, -0.6) | -0.9 b (-1.0, -0.7) | -- |
| Patients [n (%)] achieving HbA1c <7% | 72 (35%) | 88 (44%) | 25 (12%) |
| FPG (mg/dL) c | |||
| Baseline (mean) | 153 | 153 | 155 |
| Change from baseline (adjusted mean) | -19 | -25 | 12 |
| Difference from placebo (adjusted mean) (95% CI) | -31 (-37, -26) | -36 (-42, -31) | -- |
| Body Weight | |||
| Baseline (mean) in kg | 78 | 78 | 78 |
| % change from baseline (adjusted mean) | -2.8 | -3.2 | -0.4 |
| Difference from placebo (adjusted mean) (95% CI) | -2.5 b (-3.1, -1.9) | -2.8 b (-3.4, -2.2) | -- |
| JARDIANCE 10 mg + Metformin N=217 | JARDIANCE 25 mg + Metformin N=213 | Placebo + Metformin N=207 | |
|---|---|---|---|
| a Modified intent-to-treat population. Last observation on study (LOCF) was used to impute missing data at Week 24. At Week 24, 9.7%, 14.1%, and 24.6% was imputed for patients randomized to JARDIANCE 10 mg, JARDIANCE 25 mg, and placebo, respectively. b ANCOVA p-value <0.0001 (HbA1c: ANCOVA model includes baseline HbA1c, treatment, renal function, and region. Body weight and FPG: same model used as for HbA1c but additionally including baseline body weight/baseline FPG, respectively.) c FPG (mg/dL); for JARDIANCE 10 mg, n=216, for JARDIANCE 25 mg, n=213, and for placebo, n=207 | |||
| HbA1c (%) a | |||
| Baseline (mean) | 7.9 | 7.9 | 7.9 |
| Change from baseline (adjusted mean) | -0.7 | -0.8 | -0.1 |
| Difference from placebo + metformin (adjusted mean) (95% CI) | -0.6 b (-0.7, -0.4) | -0.6 b (-0.8, -0.5) | -- |
| Patients [n (%)] achieving HbA1c <7% | 75 (38%) | 74 (39%) | 23 (13%) |
| FPG (mg/dL) c | |||
| Baseline (mean) | 155 | 149 | 156 |
| Change from baseline (adjusted mean) | -20 | -22 | 6 |
| Difference from placebo + metformin (adjusted mean) | -26 | -29 | -- |
| Body Weight | |||
| Baseline mean in kg | 82 | 82 | 80 |
| % change from baseline (adjusted mean) | -2.5 | -2.9 | -0.5 |
| Difference from placebo (adjusted mean) (95% CI) | -2.0 b (-2.6, -1.4) | -2.5 b (-3.1, -1.9) | -- |
| JARDIANCE 10 mg + Metformin 1000 mg a N=161 | JARDIANCE 10 mg + Metformin 2000 mg a N=167 | JARDIANCE 25 mg + Metformin 1000 mg a N=165 | JARDIANCE 25 mg + Metformin 2000 mg a N=169 | JARDIANCE 10 mg N=169 | JARDIANCE 25 mg N=163 | Metformin 1000 mg a N=167 | Metformin 2000 mg a N=162 | |
|---|---|---|---|---|---|---|---|---|
| a Metformin total daily dose, administered in two equally divided doses per day. b p-value ≤0.0062 (modified intent-to-treat population [observed case] MMRM model included treatment, renal function, region, visit, visit by treatment interaction, and baseline HbA1c). c p-value ≤0.0056 (modified intent-to-treat population [observed case] MMRM model included treatment, renal function, region, visit, visit by treatment interaction, and baseline HbA1c). | ||||||||
| HbA1c (%) | ||||||||
| Baseline (mean) | 8.7 | 8.7 | 8.8 | 8.7 | 8.6 | 8.9 | 8.7 | 8.6 |
| Change from baseline (adjusted mean) | -2.0 | -2.1 | -1.9 | -2.1 | -1.4 | -1.4 | -1.2 | -1.8 |
| Comparison vs JARDIANCE (adjusted mean) (95% CI) | -0.6 b (-0.9, -0.4) | -0.7 b (-1.0, -0.5) | -0.6 c (-0.8, -0.3) | -0.7 c (-1.0, -0.5) | -- | -- | -- | -- |
| Comparison vs metformin (adjusted mean) (95% CI) | -0.8 b (-1.0, -0.6) | -0.3 b (-0.6, -0.1) | -0.8 c (-1.0, -0.5) | -0.3 c (-0.6, -0.1) | -- | -- | -- | -- |
| JARDIANCE 10 mg + Metformin + SU N=225 | JARDIANCE 25 mg + Metformin + SU N=216 | Placebo + Metformin + SU N=225 | |
|---|---|---|---|
| a Modified intent-to-treat population. Last observation on study (LOCF) was used to impute missing data at Week 24. At Week 24, 17.8%, 16.7%, and 25.3% was imputed for patients randomized to JARDIANCE 10 mg, JARDIANCE 25 mg, and placebo, respectively. b ANCOVA p-value <0.0001 (HbA1c: ANCOVA model includes baseline HbA1c, treatment, renal function, and region. Body weight and FPG: same model used as for HbA1c but additionally including baseline body weight/baseline FPG, respectively.) c FPG (mg/dL); for JARDIANCE 10 mg, n=225, for JARDIANCE 25 mg, n=215, for placebo, n=224 | |||
| HbA1c (%) a | |||
| Baseline (mean) | 8.1 | 8.1 | 8.2 |
| Change from baseline (adjusted mean) | -0.8 | -0.8 | -0.2 |
| Difference from placebo (adjusted mean) (95% CI) | -0.6 b (-0.8, -0.5) | -0.6 b (-0.7, -0.4) | -- |
| Patients [n (%)] achieving HbA1c <7% | 55 (26%) | 65 (32%) | 20 (9%) |
| FPG (mg/dL) c | |||
| Baseline (mean) | 151 | 156 | 152 |
| Change from baseline (adjusted mean) | -23 | -23 | 6 |
| Difference from placebo (adjusted mean) | -29 | -29 | -- |
| Body Weight | |||
| Baseline mean in kg | 77 | 78 | 76 |
| % change from baseline (adjusted mean) | -2.9 | -3.2 | -0.5 |
| Difference from placebo (adjusted mean) (95% CI) | -2.4 b (-3.0, -1.8) | -2.7 b (-3.3, -2.1) | -- |
| JARDIANCE 25 mg + Metformin N=765 | Glimepiride + Metformin N=780 | |
|---|---|---|
| a Modified intent-to-treat population. Last observation on study (LOCF) was used to impute data missing at Week 52. At Week 52, data was imputed for 15.3% and 21.9% of patients randomized to JARDIANCE 25 mg and glimepiride, respectively. b Non-inferior, ANCOVA model p-value <0.0001 (HbA1c: ANCOVA model includes baseline HbA1c, treatment, renal function, and region) c ANCOVA p-value <0.0001 (Body weight and FPG: same model used as for HbA1c but additionally including baseline body weight/baseline FPG, respectively.) d FPG (mg/dL); for JARDIANCE 25 mg, n=764, for glimepiride, n=779 | ||
| HbA1c (%) a | ||
| Baseline (mean) | 7.9 | 7.9 |
| Change from baseline (adjusted mean) | -0.7 | -0.7 |
| Difference from glimepiride (adjusted mean) (97.5% CI) | -0.07 b (-0.15, 0.01) | -- |
| FPG (mg/dL) d | ||
| Baseline (mean) | 150 | 150 |
| Change from baseline (adjusted mean) | -19 | -9 |
| Difference from glimepiride (adjusted mean) | -11 | -- |
| Body Weight | ||
| Baseline mean in kg | 82.5 | 83 |
| % change from baseline (adjusted mean) | -3.9 | 2.0 |
| Difference from glimepiride (adjusted mean) (95% CI) | -5.9 c (-6.3, -5.5) | -- |
| JARDIANCE 10 mg + Pioglitazone N=165 | JARDIANCE 25 mg + Pioglitazone N=168 | Placebo + Pioglitazone N=165 | |
|---|---|---|---|
| a Modified intent-to-treat population. Last observation on study (LOCF) was used to impute missing data at Week 24. At Week 24, 10.9%, 8.3%, and 20.6% was imputed for patients randomized to JARDIANCE 10 mg, JARDIANCE 25 mg, and placebo, respectively. b ANCOVA p-value <0.0001 (HbA1c: ANCOVA model includes baseline HbA1c, treatment, renal function, and background medication. Body weight and FPG: same model used as for HbA1c but additionally including baseline body weight/baseline FPG, respectively.) c FPG (mg/dL); for JARDIANCE 10 mg, n=163 | |||
| HbA1c (%) a | |||
| Baseline (mean) | 8.1 | 8.1 | 8.2 |
| Change from baseline (adjusted mean) | -0.6 | -0.7 | -0.1 |
| Difference from placebo + pioglitazone (adjusted mean) (95% CI) | -0.5 b (-0.7, -0.3) | -0.6 b (-0.8, -0.4) | -- |
| Patients [n (%)] achieving HbA1c <7% | 36 (24%) | 48 (30%) | 12 (8%) |
| FPG (mg/dL) c | |||
| Baseline (mean) | 152 | 152 | 152 |
| Change from baseline (adjusted mean) | -17 | -22 | 7 |
| Difference from placebo + pioglitazone (adjusted mean) (97.5% CI) | -23 b (-31.8, -15.2) | -28 b (-36.7, -20.2) | -- |
| Body Weight | |||
| Baseline mean in kg | 78 | 79 | 78 |
| % change from baseline (adjusted mean) | -2.0 | -1.8 | 0.6 |
| Difference from placebo (adjusted mean) (95% CI) | -2.6 b (-3.4, -1.8) | -2.4 b (-3.2, -1.6) | -- |
| 18 weeks (no insulin adjustment) | 78 weeks (adjustable insulin dose after 18 weeks) | |||||
|---|---|---|---|---|---|---|
| JARDIANCE 10 mg + Insulin N=169 | JARDIANCE 25 mg + Insulin N=155 | Placebo + Insulin N=170 | JARDIANCE 10 mg + Insulin N=169 | JARDIANCE 25 mg + Insulin N=155 | Placebo + Insulin N=170 | |
| a Modified intent-to-treat population. Last observation on study (LOCF) was used to impute missing data at Week 18 and 78. At Week 18, 21.3%, 30.3%, and 21.8% was imputed for patients randomized to JARDIANCE 10 mg, JARDIANCE 25 mg, and placebo, respectively. At Week 78, 32.5%, 38.1% and 42.4% was imputed for patients randomized to JARDIANCE 10 mg, JARDIANCE 25 mg, and placebo, respectively. b ANCOVA p-value <0.0001 (HbA1c: ANCOVA model includes baseline HbA1c, treatment, and region; FPG: MMRM model includes baseline FPG, baseline HbA1c, treatment, region, visit and visit by treatment interaction. Body weight: MMRM model includes baseline body weight, baseline HbA1c, treatment, region, visit and visit by treatment interaction. c p-value=0.0049 d p-value=0.0052 e p-value=0.0463 | ||||||
| HbA1c (%) a | ||||||
| Baseline (mean) | 8.3 | 8.3 | 8.2 | 8.3 | 8.3 | 8.2 |
| Change from baseline (adjusted mean) | -0.6 | -0.7 | 0 | -0.4 | -0.6 | 0.1 |
| Difference from placebo (adjusted mean) (97.5% CI) | -0.6 b (-0.8, -0.4) | -0.7 b (-0.9, -0.5) | -- | -0.5 b (-0.7, -0.3) | -0.7 b (-0.9, -0.5) | -- |
| Patients (%) achieving HbA1c <7% | 18.0 | 19.5 | 5.5 | 12.0 | 17.5 | 6.7 |
| FPG (mg/dL) | ||||||
| Baseline (mean) | 138 | 146 | 142 | 138 | 146 | 142 |
| Change from baseline (adjusted mean, SE) | -17.9 (3.2) | -19.1 (3.3) | 10.4 (3.1) | -10.1 (3.2) | -15.2 (3.4) | 2.8 (3.2) |
| Difference from placebo (adjusted mean) (95% CI) | -28.2 b (-37.0, -19.5) | -29.5 b (-38.4, -20.6) | -- | -12.9 c (-21.9, 3.9) | -17.9 b (-27.0, -8.8) | -- |
| Body Weight | ||||||
| Baseline mean in kg | 92 | 95 | 90 | 92 | 95 | 90 |
| % change from baseline (adjusted mean) | -1.8 | -1.4 | -0.1 | -2.4 | -2.4 | 0.7 |
| Difference from placebo (adjusted mean) (95% CI) | -1.7 d (-3.0, -0.5) | -1.3 e (-2.5, -0.0) | -- | -3.0 b (-4.4, -1.7) | -3.0 b (-4.4, -1.6) | -- |
| JARDIANCE 10 mg + Insulin +/- Metformin N=186 | JARDIANCE 25 mg + Insulin +/- Metformin N=189 | Placebo + Insulin +/- Metformin N=188 | |
|---|---|---|---|
| a Modified intent-to-treat population. Last observation on study (LOCF) was used to impute missing data at Week 18. At Week 18, 23.7%, 22.8% and 23.4% was imputed for patients randomized to JARDIANCE 10 mg, JARDIANCE 25 mg, and placebo, respectively. b ANCOVA p-value <0.0001 (HbA1c: ANCOVA model includes baseline HbA1c, treatment, renal function, geographical region, and background medication). | |||
| HbA1c (%) a | |||
| Baseline (mean) | 8.4 | 8.3 | 8.3 |
| Change from baseline (adjusted mean) | -0.9 | -1.0 | -0.5 |
| Difference from placebo (adjusted mean) (95% CI) | -0.4 b (-0.6, -0.3) | -0.5 b (-0.7, -0.4) | -- |
| Mild and Moderate Impairment b | |
|---|---|
| JARDIANCE 25 mg | |
| a p-value <0.0001 (HbA1c: ANCOVA model includes baseline HbA1c, treatment, renal function, and background medication) b eGFR 30 to less than 90 mL/min/1.73 m 2 - Modified intent-to-treat population. Last observation on study (LOCF) was used to impute missing data at Week 24. At Week 24, 24.6% and 26.2% was imputed for patients randomized to JARDIANCE 25 mg and placebo, respectively. | |
| HbA1c | |
| Number of patients | n=284 |
| Comparison vs placebo (adjusted mean) (95% CI) | -0.5 a (-0.6, -0.4) |
| Placebo N=2333 | JARDIANCE N=4687 | Hazard ratio vs placebo (95% CI) | |
|---|---|---|---|
| a Treated set (patients who had received at least one dose of study drug) b p-value for superiority (2-sided) 0.04 c Total number of events | |||
| Composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke (time to first occurrence) b | 282 (12.1%) | 490 (10.5%) | 0.86 (0.74, 0.99) |
| Non-fatal myocardial infarction c | 121 (5.2%) | 213 (4.5%) | 0.87 (0.70, 1.09) |
| Non-fatal stroke c | 60 (2.6%) | 150 (3.2%) | 1.24 (0.92, 1.67) |
| Cardiovascular death c | 137 (5.9%) | 172 (3.7%) | 0.62 (0.49, 0.77) |
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
Ready to save on Jardiance?
Compare prescription prices at over 70,000 pharmacies and start saving today—no enrollment required.
Compare Jardiance Prices