Use of New Medications to Treat Type 2 Diabetes: Case Studies

Transcription

1 Number f Medicatin Classes 12/2/2014 Use f New Medicatins t Treat Type 2 Diabetes: Case Studies HTN and DM: Drug Classes in US Over Past Half Century peripheral -1 blckers - blckers ACE Inhibitrs Ca+ channel blckers Angitensin II receptr blckers SGLT-2 I Dpamine agnists Renin inhibitrs Glinides DPP-4 inhibitrs Amylinmimetics Receptr Agnists Bile acid sequestrants Anne Peters, MD Prfessr, USC Keck Schl f Medicine Directr, USC Clinical Diabetes Prgrams adrenergic neurnal blckers central -2 agnists diuretics Biguanides 2 vasdilatrs Sulfnylureas 1 insulin Thiazlidinedines -glucsidase inhibitrs Biguanides Slide frm: Inzucchi S ADA-EASD Psitin Statement: Management f Hyperglycemia in T2DM 1. Patient-Centered Apprach...prviding care that is respectful f and respnsive t individual patient preferences, needs, and values - ensuring that patient values guide all clinical decisins. Gauge patient s preferred level f invlvement. ADA/EASD Recmmendatins fr HbA 1c Less stringent (7.5% - 8%) < 7% Mre stringent (as clse t 6% as pssible) Shared decisin making final decisins re: lifestyle chices ultimately lies with the patient. Explre, where pssible, therapeutic chices. Utilize decisin aids. Lng diabetes duratin Shrt life expectancy Cmplicatins, cmrbidities Histry f severe hypglycemia Shrt diabetes duratin Lng life expectancy N CVD Diabetes Care 2012;35: Diabetlgia 2012;55: Inzucchi SE, et al. Diabetes Care. 2012;35: MC is an 87 y female with a 10 20? year histry f type 2 diabetes. She is a very pr histrian and when she came t see me tw years ag she had an HbA1c = 12% with symptms. She was blind in her left eye and had severe retinpathy in her right eye and wanted tight BG cntrl. She had had cln and urethral cancer, was getting sterid injectins int her knees, culd barely walk and had CHF, RI, renal stnes, PUD, asthma, HTN, GERD, liver disease etc Her meds were levxyl and lsartan. She stated she culdn t take TZD s, metfrmin, Januvia. She did n SMBG and refused t learn. She wuld nt give an injectin. She culd nt attend clinic ften due t transprtatin difficulties. Of nte, she weighed 10 punds at birth and is f French Sephardic Jewish descent. She grew up in Algeria. What is her target and what d yu d? 1

2 Mre data: her C-peptide level = 9.4 ng/ml with a BG level = 244 mg/dl. Creatinine = 1.6 mg/dl, egfr = 39 She had chrnic LE edema and a nnhealing left ft abscess. I started her n glimepiride 1 mg/day. Discussed lifestyle changes. Uptitrated t 2 mg based n a lack f symptms f hypglycemia (phne fllwup). At her next visit 3 mnths later her HbA1c = 8.1% Three mnths later her HbA1C = 7.4%. She was eating much better, n lnger getting sterid injectins, seeing a new pdiatrist. Shrtly thereafter she develped a diffuse pruritic rash that was like the measles which turned ut t be an allergic reactin t glimepiride. Therefre, I switched her t prebreakfast/dinner repaglinide. After a phase f feeling dizzy/having jint pain and ther side effects she learned t tlerate it. At her last visit she turned 89, her A1C = 7.2%, n rash r hypglycemia and she functins! Secretin and Inactivatin Mixed meal Intestinal release DPP-4 Inhibitrs A1c Sitagliptin reductin Weight Saxagliptin neutral N Linagliptin hyps Algliptin Few SE s/pill active DPP-4 inhibitr Agnists A1c Exenatide reductin Weight Liraglutide lss Albiglutide N hyps Injectable Dulaglutide GI side effects DPP-4 inactive Adapted frm Rthenberg P, et al. Diabetes. 2000;49(suppl 1):A39. Case #2 SR is a 76 y male with type 2 DM and ESRD n dialysis He had been n 70/30 insulin twice daily which caused frequent episdes f hypglycemia, especially when he didn t eat. Changed t an MDI regimen with Lantus and premeal rapid acting insulin but this was t cmplicated fr him t adhere t. Case #2 Gals: reduce hypglycemia, lwer cmplexity, imprve quality f life Added sitagliptin 25 mg, reduced premeal insulin dse by 50%, cntinued his basal insulin Eventually his premeal insulin was stpped, his basal insulin was cntinued and his SMBG reduced t nce daily 54 year ld white man newly diagnsed with prly cntrlled type 2 diabetes Ntable in his histry was weight gain since a back injury and light duty at wrk Decreased exercise due t pain PMH: HTN, disc disease, n knwn CVD Metfrmin (MET) 500 mg BID On n ther medicatins at first visit 2

3 General Healthy white male - Weight 302 lbs (137 kg) - Height BMI 39.8 Cardiac Pulse 100 and regular Bld pressure (BP) 142/100 mm Hg Visin N retinpathy A1C 9.2% Bld glucse 216 mg/dl (12 mml) Creatinine 1.0 mg/dl Ttal chlesterl 302 mg/dl Triglycerides (TG) 846 mg/dl Lw-density lipprtein (LDL) nt calculated due t elevated TG High-density lipprtein 42 mg/dl Thyrid functin within nrmal limits Increase Metfrmin t 1000 mg BID; glimepiride added BP treated with ACE-I and Beta Blcker Lipids treated with statin Patient wrked n weight lss with n change A1C imprved t 8.1% Exenatide was started at 5 μg BID and increased t 10 μg BID after ne mnth Glimepiride dse reduced by 50% Minimal nausea at the start f exenatide treatment Patient began lsing weight because f a decrease in his appetite Fllw-up visit at 3 m after initiatin f exenatide Weight fell frm 302 t lbs (137 t 133) ( 9.6 lbs) (-4.4 kg) A1C decreased t 6.4% Bld pressure 120/80, HR 72 Ttal chlesterl = 108, TG = 130, LDL = 54 Fllw-up visit at 3 years after initiatin f Exenatide On exenatide 10 mcg BID plus metfrmin Maintained his weight lss with a weight f A1C ranges frm % Cntinues t be mre physically active 3

4 Urinary glucse excretin (g/day) 12/2/2014 The Prspect f SGLT2 Inhibitin RENAL HANDLING OF GLUCOSE (180 L/day) (900 mg/l) = 162 g/day SGLT2 Inhibitrs Lwer Renal Threshld fr Glucse Excretin (RT G ) T2DM + SGLT2 inhibitin Healthy 180 mg/dl T2DM 240 mg/dl RT G RT G RT G 90% SGLT 2 10% S G L T SGLT2 inhibitin Plasma glucse (mg/dl) NO GLUCOSE Adapted with permissin frm Abdul-Ghani MA, DeFrnz RA. T2DM = type 2 diabetes mellitus. 1. Abdul-Ghani MA, DeFrnz RA. Endcr Pract. 2008;14(6): Nair S, Wilding JP. J Clin Endcrinl Metab. 2010;95(1): Canagliflzin and Dapagliflzin Warnings and Precautins Hypglycemia: risk with secretaggues and/r insulin Genital myctic infectins Vlume depletin/rthstatic changes Hypersensitivity Increased LDL Bladder cancer: dn t use if active; use with cautin if prir histry f bladder cancer (dapagliflzin nly) Adding an SGLT-2 Inhibitr AK is a 54 y male with a 10 year histry f prly cntrlled type 2 diabetes. Had tried all therapies, including metfrmin, SU, piglitazne, exenatide, liraglutide, basal and prandial insulin in varius cmbinatins. Althugh his A1C was ccasinally as lw as 7.2%, usually it was %. His BMI = 29 kg/m 2 with n cmplicatins. His last clinic visit he had an HbA1C = 9.7%, did very rare SMBG and was taking metfrmin, glimepiride and basal insulin. Canagliflzin was added and insulin dse reduced by 50%. RxList, Adding an SGLT-2 Inhibitr His wrds abut the canagliflzin: This mrning, I awke early (4:45am) and tested and was feeling rested and raring t g. I was a 71. At 6:30am, withut taking medicatin nr eating anything, I retested and I was a 96, which seemed nrmal based n my understanding f hw bld glucse levels wrk at that time f the day. I tk my Invkana, metfrmin (2000mg) and Glimepiride (2mg) at 7:00am and then ate breakfast. An hur after a well balanced breakfast I was at 117. Adding an SGLT-2 Inhibitr Yesterday, I tested a half dzen times with numbers between , with the exceptin f a 226 spike ccurring ne-hur after breakfast (it was a 114 at 7am) but it was als befre taking my mrning medicatin. I didn't remember that the instructins strngly suggested taking the Invkana prir t breakfast. Last night, prir t dinner I was at 136 s I tk 20cc f Lantus. Tday, taking the Invkana befre breakfast, as prescribed, I've had ne f thse really gd mrnings where I dn't have a dullness fllwing the first meal f the day. 4

5 Case #4 Case #4 MT is a 69 y male with a 15 year histry f type 2 diabetes. He had CVD, HTN, chrnic LBP, and psriasis. He was referred t start n an insulin pump. He was n lng acting insulin 100 units BID and premeal insulin at a dse f units rapid acting insulin premeals. He als tk 120 mcg pramlinitide befre meals, metfrmin and sitaglitptin. He was 5 10 tall and weighed 276 punds. His A1C = 7.3%. He had an extremely limited area where he culd inject due t his skin issues and the 8 daily injectins he was giving daily was causing marked skin irritatin. Therefre, a nce weekly RA was added t his regimen. The sitagliptin and pramlintide were stpped and his insulin dses were reduced by 20%. Case #4 After 3 mnths his lng acting insulin dse was reduced frm 200 units per day t 60 units at bedtime. His mealtime insulin dses were reduced t units per meal and he ften gave n insulin fr lunch. His weight fell by 24 punds. He had n GI side effects r severe hypglycemia. An SGLT-2 inhibitr was added and his diuretic dse was reduced and his premeal insulin tapered t zer On the cmbinatin f metfrmin, a nce weekly RA, an SGLT-2 inhibitr and basal insulin 40 units at bedtime his A1C was 7.0% and his insulin injectin burden changed frm 8 injectins per day t 1 daily and 1 weekly. Final Case Medicatins Aren t Always the Answer FT was a 56 y male with a tw year histry f T2DM when he first came t see me. He was n an SU and metfrmin with an A1C f 10.4%. He had n cmplicatins and was therwise well. 1 year prir his nly child, a 21 year ld sn, was killed by a drunk driver. He said after a year f grief he was nw ready t take care f his health. He wasn t. Final Case Over the next ten years we tried adding every therapy, frm TZD s t DPPIV-I s t insulin t all RA s ccasinally his A1C wuld fall int the mid 7% range, but it wuld never stay there and was generally ~10%. He frgt t d SMBG r self-titrate, he wuld miss appintments, he wuld gain and lse weight, stp and start exercise. Final Case His BMI ranged frm kg/m 2. We kept trying. After 11 years his A1C = 6.6% and his BMI = 27 kg/m 2. What happened? He had decided t change. His meds were nw: Metfrmin Canagliflzin Liraglutide All medicatins that helped with his lifestyle changes 5

6 Chsing the Apprpriate Therapy SMBG? Side effects? Cst? Ease f use? There is N Such Thing as the Miracle Pill Cntraindicatin? Effectiveness? Extra glycemic effects? Weight? Patient Needs/ Desires Inzucchi S, et al. Diabetes Care. 2012;35: THANK YOU 6