Presentation on theme: "JARDIANCE: Newly Approved Drug to Lower HbA1C in Type-2 diabetes"— Presentation transcript:
1 JARDIANCE: Newly Approved Drug to Lower HbA1C in Type-2 diabetes Presented By:Rahul Patel, MS, PharmD. Candidate 2015Dr. Sam Shimomura, Associate Dean,Western University of Health SciencesDate:09/25/2014
2 DisclosureI, Rahul Patel, have no conflict of interest to disclose.
3 Objectives Pharmacists will be able to: Describe SGLT2 inhibitors Compare available SGLT-2 inhibitorsIdentify ideal candidates for SGLT2 inhibitorsPost test questions should reflect 2 objectives,( symptoms, ideal candidate, pregnancy)
4 Introduction1Diabetes mellitus is a chronic disease often requiring complex treatment regimens to prevent long-term complications.According to the 2012 statistics from CDC, 29.1 million people have diabetes.The total direct and indirect estimated cost of the disease in 2014 is 245 billion.
5 Introduction (Cont’d) Type 2 diabetes is characterized by 3 factorsPersistent hyperglycemiaImpaired β-cell functionInsulin resistance
6 SGLT2 Inhibitors: A Novel Class2 Sodium-Glucose Co-transporter 2 (SGLT-2) inhibition works directly on glucose, independent of β-cell function and insulin90% of the glucose is reabsorbed by SGLT2 , remaining 10% by SGLT1
7 Currently Approved SGLT2 Inhibitors Invokana (canagliflozin)Mfg by: Janssen Pharmaceuticals, Inc.Licensed from Mitsubishi Tanabe Pharma CorporationApproved in Mar’2013Farxiga (dapagliflozin)Mfg By: Bristol-Myers Squib CompanyMkt By: AstraZeneca Pharmaceuticals LPApproved in Jan’2014Jardiance (empagliflozin)Mfg By: Eli Lilly and CompanyApproved in Aug’2014The FDA is requiring five postmarketing studies for Invokana: a cardiovascular outcomes trial; an enhanced pharmacovigilance program to monitor for malignancies, serious cases of pancreatitis, severe hypersensitivity reactions, photosensitivity reactions, liver abnormalities, and adverse pregnancy outcomes; a bone safety study; and two pediatric studies under the PREA.
8 Jardiance Efficacy as Monotherapy3 Results at Week 24 From a Placebo-Controlled Monotherapy Study of JARDIANCE
9 Efficacy in Combination3 Results at Week 24 From a Placebo-Controlled Study for JARDIANCE used inCombination with MetforminMake table
10 Efficacy in Combination3 Results at Week 24 From a Placebo-Controlled Study for JARDIANCE in Combinationwith Metformin and Sulfonylurea
11 Adverse Effects of Jardiance3 Adverse Reactions Reported in ≥2% of Patients Treated with JARDIANCE and Greater than Placebo in Pooled Placebo-Controlled Clinical Studies of JARDIANCE Monotherapy or Combination Therapy
13 Jardiance vs Farxiga Jardiance Farxiga Indication As an adjunct to diet and exercise to improve glycemic control in adults with T2DMUsual DoseStarting dose: 10 mg by mouth dailyMaximum dose: 25 mg once dailyStarting dose: 5 mg by mouth dailyMaximum dose: 10 mg once dailyDosing In Renal ImpairmentGFR ≤ 45 ml/min/1.73m2, end-stage renal disease, or dialysis: contraindicatedGFR 30 to 60 ml/min/1.73m2: not recommendedGFR ≤ 30 ml/min/1.73m2, end-stage renal disease, or dialysis: contraindicatedDosing In Hepatic ImpairmentNo dosage adjustment necessaryUse is not recommended in severe hepatic impairment (has not been studied)Drug InteractionsInsulin or Insulin Secretagogues: increases risk of hypoglycemiaNo significant drug interactionsAdministrationTake in the morning, with or without foodMetabolismPrimarily metabolized by UGT2B7, UTG1A3, UGT1A8, and UGT1A9Primarily metabolized by UGT1A9 to an inactive metaboliteWeak substrate of P-glycoprotein
14 Jardiance vs Farxiga4 Jardiance Farxiga Pharmacokinetics Onset of action: within 24 hoursProtein binding: 86.2%; not affected by renal or hepatic impairmentOral bioavailability: 79%Half-life elimination: 12.4 hoursExcretion: urine (54.4%; half as unchanged drug); feces (41.2%, primarily unchanged drug)Protein binding: 91%; not affected by renal or hepatic impairmentOral bioavailability: 78%Half-life elimination: 12.9 hoursExcretion: urine (75%; <2% as unchanged drug); feces (21%, 15% as unchanged drug)Most common Adverse Reactions (Frequency)Female genital infection (6.4% - 5.4%)Urinary tract infection (7.6% - 9.3%)Upper respiratory tract infections (4.0% - 3.1%)Increased urination (3.4% - 3.2%)Female genital infection (6.9% - 8.4%)Urinary tract infection (4.3% - 5.7%)Price10 mg or 25 mg (30): $361.065 mg or 10 mg (30): $347.04UGT enzyme inducers include rifampin, phenytoin, phenobarbital, and ritonavir.UGT = uridine glucuronyl transferase
15 Which SGLT-2 inhibitor to use ? Efficacy comparison* as monotherapy compared to placebo in 24 weeks trialJardiance(10mg,25mg)Farxiga(5mg,10mg)Invokana5(100mg,300mg)HbA1C reduction (%)FPG reduction (mg/dL)31-3636-43Weight Loss (in Kg)SBP reduction (mmHg)*Note: comparison in individual trials and not in head to head clinical trials*Note: comparison in individual trials and not in head to head clinical trials
16 Which SGLT-2 inhibitor to use ? Farxiga :Carries a warning of Bladder cancer risk.Newly diagnosed Bladder cancer has been reported in 0.17% of subjectsUse not recommended in Hepatic Impairment (not studied )Jardiance:Can be used in Hepatic ImpairmentInvokana:Use not recommended in Hepatic Impairment( not studied)Dose related Hyperkalemia>5.4mEq/mL(12%-27%), ≥6.5mEq/mL (2%)The FDA is requiring five postmarketing studies for Invokana: a cardiovascular outcomes trial; an enhanced pharmacovigilance program to monitor for malignancies, serious cases of pancreatitis, severe hypersensitivity reactions, photosensitivity reactions, liver abnormalities, and adverse pregnancy outcomes; a bone safety study; and two pediatric studies under the PREA.
17 Effects of SGLT-2 inhibitors Benefits:HbA1C decrease 0.5-1%Weight LossNo edemaOnce a day dosingA little decrease of SBPMinimal HypoglycemiaDrawbacks:UTI, balanitis, mycotic vulvovaginal infectionMild transient decrease in eGFRNot studied in Type 1 diabetes
18 Current Place in Therapy FDA approved as adjunct to diet and exercise to control blood glucose.Also studied in combination with metformin, SU, insulin, pioglitazoneCan be used as second line, after metformin ( because metformin is more studied and approved as first line), however, its cost should be considered.It may be debatable as a second line or first line therapy, because metformin has greater HBA1c control, its weight neutral and cheap and have more data. But as third line therapy it is probably best suited if the patient is a candidate. But having said that, ultimately it’s physician’s and patients’ choice.
19 ConclusionSince the mechanism of action is independent of the insulin and β-cell function, theoretically it can be used as long as renal function is okay.It is a new drug ,therefore should be used with extra monitoring, renal function especially.Long term effects unknownNo studies have been done to see that if the decrease in HbA1C correlates with the decrease in macro and micro vascular complications associated with diabetes.
20 Ideal patientWhich of the following is a candidate for therapy with Jardiance ?A 25 year old pregnant woman with Type 2 diabetes.A 38 year old male, obese patient with Type 2 diabetes having normal kidney functionA 68 year old male patient with Type 2 diabetes.A 25 year old male patient with Type 1 diabetes
21 References1.2. Ele Ferrannini & Anna Solini, SGLT2 inhibition in diabetes mellitus: rationale and clinical prospects, Nature Reviews Endocrinology 8, (August 2012)3. Jardiance package insert4. Farxiga package insert5. Invoka package insert