Presentation on theme: "Katee Lira, PharmD PGY2 Ambulatory Care Pharmacy Resident"— Presentation transcript:
1 Sodium-glucose co-transporter 2 (SGLT2) inhibitors and their place in therapy Katee Lira, PharmDPGY2 Ambulatory Care Pharmacy ResidentSt. Vincent Joshua Max Simon Primary Care CenterSeptember 18, 2014This speaker has no actual or potential conflicts of interest to disclose in relation to this presentation.
2 Objectives Recall the mechanism of action of SGLT2 inhibitors List potential benefits and concerns of SGLT2 inhibitorsRecognize available SGLT2 inhibitors and appropriate dosingIdentify place in therapy for SGLT2 inhibitors
3 Components that Affect Hyperglycemia Which of these components do you think SGLT-2 Inhibitors affect?Response: increased glucose reabsorptionCatch line from drug rep: You can eat your cake and pee it too? I don’t like this because this may give patients the impression that they don’t have to watch their diet.DeFronzo RA. Diabetes. 2009;58:
4 How Do SGLT2 Inhibitors Work? Glucose in bloodNORMALLY ALL FILTERED GLUCOSE IS REABSORBEDHighly specific for the kidney and SGLT2 transporterIt works by blocking the reabsorption of glucose (blood sugar) by the kidney, increasing glucose excretion, and lowering blood glucose levels in diabetics who have elevated blood glucose levelsEffectiveness is independent of insulin -- This mechanism of action is independent of insulin so this could be a benefit for someone who is having insulin resistance.Bailey CJ, Day C. SGLT2 inhibitors: glucuretic treatment for type 2 diabetes. BR J Diabetes Vasc Dis. 2010; 10:GlucosuriaChao EC, et al. Nat Rev Drug Discovery. 2010;9:
5 What % A1c Reduction will SGLT2 Inhibitors Have? 0.5%1%1.5%2%DPP4 inhibitorsSGLT2 inhibitorsTZDsMetforminSulfonylureasDiabetes Care 2014;37: S14-79.
6 Highlights of SGLT2 Inhibitors Indication: adults with type 2 diabetes (T2DM)Not approved for <18 years old, T1DM, or DKAOngoing studiesPediatricsCV outcomesBenefitsWeight reduction: ~2-3kgSystolic blood pressure lowering: ~3-5mmHgLow risk of hypoglycemiaSystolic blood pressure lowering due to osmotic diuresisA1c lowering: ~1% (many different results ranging %)75g urine glucose = 300kcal/dayWeight loss observed with monotherapy and as add-on combination therapyLow risk of hypoglycemia by itself. May have hypoglycemia in combination with medications that cause hypoglycemiaPost marketing studies include: CV outcomes trial, pharmacovigilance program to monitor for serious side effects, a bone safety study, two pediatric studiesThoretically, may be used for kids and Type1 diabetics in the futureList JF, et al. Diabetes Care. 2009;32: (for weight reduction)Stenlof K, et al. Diabetes Obes Metab. Published online January 24, (BP and A1c reduction)List JF, et al. Diabetes Care. 2009;32:Stenlof K, et al. Diabetes Obes Metab. Published online January 24, 2013.Invokana® [package insert]. Titusville, NJ: Janssen Pharmaceuticals, IncFarxiga™ [package insert. Wilmington, DE: AstraZeneca
7 FDA Approved SGLT2 Inhibitors AgentCanagliflozin INVOKANA®Dapagliflozin FARXIGA™EmpagliflozinJARDIANCE®DosingInitial: 100mg dailyMax: 300mg dailyInitial: 5mg dailyMax: 10mg dailyInitial: 10mg dailyMax: 25mg dailyAdministrationBefore the first meal of the dayIn the morning with or without foodRenal Dose AdjustmentsYesCost~$350 for 30 tabletsTBDPatient AssistanceAvailableTalking points:-When you increase dose therapies-Other agents: agent being studied with renal impairmentCurrently not available but being studied: Ipragliflozin and EmpagliflozinPrior to initiation: assess renal function Discontinue canagliflozin if GFR is consistently below 45mL/min Discontinue dapagliflozin if GFR is consistently below 60mL/minBoth are Pregnancy Category C No well controlled studies have been conducted in pregnant womenis not indicated for patients with type 1 diabetes, diabetic ketoacidosis, severe renal impairment, or end-stage renal disease or for patients receiving dialysis. It is the third oral SGLT2 inhibitor to receive FDA approval. Urinary tract infections and female genital infections were the most common adverse effects observed in the clinical trials. must conduct 4 postmarketing studies, including the completion of a cardiovascular outcomes study now underway, and 3 others delving into pediatric issues. d/c if crcl<45. dose 10mg starting and max 25mg once daily in the morningCost: Wholesale price of $8.77/tablet--FYI—Dapagliflozin Renal dosingGFR <60mL/min – not recommendedGFR <30mL/min –contraindicatedCanagliflozin Renal dosingGFR 45 – <60mL/min – 100mg dailyGFR 30 – 45mL/min – not recommendedGFR<30mL/min – contraindicatedInvokana Patient assistance:12 months at no cost if private insuranceMaximum savings of $3900 annuallyFarxiga Patient assistance:Maximum savings of $346 per 30‑day supplyInvokana® [package insert]. Titusville, NJ: Janssen Pharmaceuticals, IncFarxiga™ [package insert]. Wilmington, DE: AstraZenecaJardiance® [package insert]. Ridgefield, CT. Boehringer Ingelheim Pharmaceuticals, Inc
8 Warnings for SGLT2 Inhibitors Adverse drug reactionsPrecautionsIncreased urinationVaginal yeast infectionsUrinary tract infectionsNasopharyngitis (dapagliflozin)HypotensionImpairment in renal functionHyperkalemiaHypoglycemiaHypersensitivityIncrease in LDLBladder cancer (dapagliflozin)hypoglycemia (in combination with insulin or insulin secreatgogues)Talk about monitoring for patient and physiciansHypotension- assess volume status and correct hypovolemia in patients with renal impairment, the elderly, in patients with low systolic blood pressure or on diuretics, ACE inhibitors, or ARBsImpairment in renal function- increase serum creatinine and decreases GRFHyperkalemia- monitor potassium levels in patients with impaired renal function or those predisposed to hyperkalemiaGenital mycotic infectionscan cause dehydration, leading to a drop in blood pressure (hypotension) that can result in dizziness and/or fainting and a decline in renal function. The elderly, patients with impaired renal function, and patients on diuretics to treat other conditions appeared to be more susceptible to this riskMalignancies: bladder and breast, not significantly different% UTI 4%, 4.6%, 12.5%, and 5.7% for placebo, DAPA 2.5mg, 5mg, and 10mg groups; 8%, 4%, 7%, and 8%; 6.2%, 3.9%, 6.9%, and 5.3%; 8.4% DAPA vs 4.1% placebo% genital infections 1.3%, 7.7%, 7.8%, and 12.9% for placebo, DAPA 2.5mg, 5mg, and 10mg groups; 5%, 8%, 13%, and 9%; 0.7%, 3.9%, 6.2%, and 6.6%; 7.2% DAPA vs 2.0% placebo% hypoglycemia 2.7%, 1.5%, 0%, and 2.9% in patients in placebo, DAPA 2.5mg, 5mg, and 10mg groups; 3%, 2%, 4%, and 4%; 4.8%, 7.1%, 6.9%, and 7.9%ISMP High Alert Medication – Dispense with Medication GuideInvokana® [package insert]. Titusville, NJ: Janssen Pharmaceuticals, IncFarxiga™ [package insert. Wilmington, DE: AstraZeneca
9 Place in Therapy – Monotherapy Recent-onset diabetes and mild hyperglycemia (A1c≤7.5%)Metformin is preferredIf intolerance or contraindication to metforminSGLT2 inhibitors compared to placeboDecreasing A1cDecrease fasting glucoseGuidelines provide no preferenceMay consider SGLT2 inhibitorsRenal contraindication so going to be similar to metformin – not a great alternative for these patientsDecrease A1c by ~1%Patient centered approach – take into consideration previously mentioned factors, weigh pros and cons of each agent to decideDiabetes Care 2014;37: S14-79.Ferrannini E, et al. Diabetes Care. 2010;33(10):
10 Place in Therapy – Combination Therapy Initial A1c >7.5% – start dual therapyTarget A1c not reached in 3 months with metformin – add second agentNo preferred agent to be combined with metforminSGLT2 inhibitors studies have demonstrated improved glycemic control with combination and add-on therapyMetforminSulfonylureaThiazolidinedioneInsulinCan consider SGLT2 inhibitors in combination with metforminPatient centered approach – take into consideration previously mentioned factors, weigh pros and cons of each agent to decideSome Studies looked at dual and some at tripleInsulin was basal or basal/prandial?Bailey, et al.Add-on to metformin in patients inadequately controlled with metformin aloneFavorable safety parameters and tolerabilityStudy found improved glycemic control with metformin + SGLT-2 inhibitorCombination is not associated with risk for hypoglycemiaAdd-on to glimepiride in patients poorly controlled sulfonylurea therapySignificantly improved mean A1CReduced weightWell-toleratedAdd-on to insulin in patients poorly controlled with insulinSustained effectiveness and stable tolerabilityLess likely to D.C or require insulin up-titration due to poor glycemic control versus placeboIncreased frequency of weight loss and reduced frequency of peripheral edema over timeDiabetes Care 2014;37: S14-79.Bailey CJ, et al. Lancet. 2010;375(9733):Strojek K, et al. Abstract 870. EASD 2010.Wilding JPH, et al. Abstract 78-OR. ADA 2010.Bailey CJ et al. Abstract 988-P. ADA 2011.
11 Patient Centered Approach When Considering SGLT2 Inhibitors ProsConsEffectiveness independent of insulinCan ↓ A1c by ~1%Combine with other oral anti-diabetics and insulinLow risk for hypoglycemiaSmall amount of weight lossSmall ↓ in blood pressureAdequate renal function required↑ urinary frequencyElectrolyte disturbances↑ risk of UTIs and vaginal yeast infectionsOrthostatic hypotensionLipid abnormalities (↑ LDL)CostPatient centered approach – take into consideration previously mentioned factors, weigh pros and cons of each agent to decidePatient factors:Patient preferencesDuration of diagnosisAgeKidney or liver dysfunctionComorbiditiesMedication factors:Efficacy (A1c lowering)CostPotential side effectsEffects on weightRisk of hypoglycemiaMany Considerations to take into account when determining appropriate Drug Therapy:Nonglycemic effects: Effects of individual therapies on CVD risk: HTN, hyperlipidemiaA1C: Baseline, Goal, Expected reductionNon-glycemic effects, Duration of DM, Age, Organ function, Comorbidities (Heart failure, Alcoholism, Cognitive function, Dexterity, COSTDiabetes Care 2014;37: S14-79.
12 Assessment QuestionWhich of the following is a counseling point to tell a patient being started on canagliflozin?Will cause significant weight lossTake before the last meal of the dayMay increase your risk of urinary tract infectionsHas a high risk of hypoglycemia in combination with metforminConclusion: (for slide before)Novel mechanism of action: Novel: of a new kind; different from anything seen or known before: a novel idea. Does not mean that this new class is going to “cure” diabetesIdeal place in therapy: add on to metforminConsider individual patient factors and weigh pros/consJust approved: empagliflozin (Jardiance)Should be taken before the first meal of the dayLow likelihood of hypoglycemia unless in combination with another agent that causes hypofglycemia (metformin does not)Will cause a small amount of weight loss. Also, any oral anti-diabetic agent should be used in combination with diet and exercise.
13 Sodium-glucose co-transporter 2 (SGLT2) inhibitors and their place in therapy Katee Lira, PharmDPGY2 Ambulatory Care Pharmacy ResidentSt. Vincent Joshua Max Simon Primary Care CenterSeptember 18, 2014I would like to open the floor up for questions at this time.This speaker has no actual or potential conflicts of interest to disclose in relation to this presentation.