!"#$%&%'(!)*+'(,(&)%-!'(.#!%('"./0%(( /1#).!(&2()!(((

Transcription

1 !"#%&%'(!)*+'(,(&)%-!'(.#!%('"./0%(( /1#).!(&2()!((( 26%5&"7%'( At the end of this presentation, participants should be able to: Evaluate the emerging role of GLP-1 Agonists for weight loss Understand SGLT2 inhibitors in T2DM Explain the role of new insulin therapies in the treatment of Type 2 Diabetes Respond to questions regarding the use of therapies in a specific patients #-+%0#(+"--3.%#!24()!(0!-(5!%(( ( (

2 GLP-1 R Agonists (DM) Albiglutide (Tanzeum ) Dulaglutide (Trulicity ) GLP-1 R Agonist (Obesity) Liraglutide (Saxenda) DPP-4 Inhibitors Linagliptin (Tradjenta ) Linagliptin/metformin (Jentadueto ) SGLT-2 Inhibitors Empagliflozin (Jardiance ) Empagliflozin/metformin (Synjardy ) SGLT-2 Inhibitors/DPP-4 Inhibitor Empagliflozin/Linagliptin (Glyxambi ) Rapid Acting Insulin Lispro (Humalog U-200 Kwikpen ) Long Acting Insulin Degludec (Tresiba ) Insulin Glargine (Toujeo U-300) Insulin Glargine (Basaglar U-100 Kwikpen ) Insulin human injection (Humulin R U-500 Kwikpen ) Inhaled Insulin Insulin human inhalation powder (Afreeza ) Mixed Insulin Insulin Degludec/Insulin Aspart (Ryzodeg 70/30 ) +0/38()%5%/&2)(#+2-"'&9( 0")#+0*&"!%( :'#;%-!#<=(3(2%'"&>( +0/38(.2!*0#&%'(-*.%)2*'(?*-5&"2-'("-(1*.#-'( GLP-1: Secreted upon the ingestion of food 5/##"+.).%"2+"3)%46)) /+61&+.)%--+"2"+) =,-'%)&+,,.() )9,1&#.+< ") -#."-/%462%,) 0,1&%0#4).+&/+"2#4) :+"%)&+,,.() ;4'%4&+.)0,1&#.+< ") 24.1,24).+&/+"2#4) 728+/() ) )9,1&%0#4)/+61&+.) '+-%"2&)0,1&#.+)#1"-1")!"#%&'()) )*+,-.)/+01,%"+)0%."/2&) +-"3240)!"#"%&'()*+,#-./#"*0!"#%&"'&()* "!"#"%&'(:"&;;',<./#"*,-.+/"012*%3"4./&5,122=41>56?1@8?99!"#"%&'(A"BCDE-./#"*06%/7)+338%/0122>4@2617?>8177@4!"#"%&'(!&BCD/&!F06%/7)+);012234?=617281>2

3 0")#+0*&"!%(:'#;%-!#<=( (#( +0/383)(#+2-"'&((4"&1(-%4( "-!"5#&"2-(3(4%"+1&(02''( 0")#+0*&"!%(:'#;%-!#<=(3(2%'"&>( Indication: Adjunct to lifestyle (reduced calorie diet and increased physical activity) for chronic weight management In individuals with a BMI of >30 kg/m 2 In individuals with a BMI of >27 kg/m 2 in the presence of at least one weight-related comorbidity such as HTN, Diabetes, or Dyslipidemia G"H/,I"J&/;C&+K+,L+,%'&("#+',6M##J6NNOOO0,'P'8J+0C'(N;"H/,I"0JI%0-CC/;;/I9N9>N1> '#;%-!#<('#?%&>(#-!(%??"5#5>( 50"-"5#0(&)"#0'( Three 56-week, randomized, double-blind, placebo-controlled trials All patients were overweight ( kg/m 2 ) or obese >30 kg/m 2 Dosage titration: to 3 mg daily during a 4-week period All patients received instructions throughout the trial for: A reduced calorie diet (approximately 500 kcal/day deficit) Exercise counseling - minimum 150 mins/week) )%'*0&'(2?(&1%(50"-"5#0(&)"#0( Baseline mean (SD) (kg) % change from baseline (LSMean) Difference from placebo (LSMean) (95% CI) Study 1 (Obesity/overweight + comorbidity) Saxenda N= (21.2) Placebo N= (21.7) Study 2 (Obesity/overweight + Type 2 DM) Saxenda N= (21.9) Placebo N= (21.3) Study 3 (Obesity or overweight + comorbidity following > 5% weight loss with diet) Saxenda Placebo N=212 N= (20.8) 98.7 (21.2) * (-5.2;-3.8) -3.7* (-4.7;-2.7) -5.2* (-6.8;-3.5) % Patients losing > 5% BW 62.3% 34.4% 49.0% 16.4% 44.2% 21.7% Difference from placebo (LSMean) (95% CI) 27.9* (23.9;31.9 ) 32.6* (25.1;40.1) 22.6* (13.9;31.3) M##J6NNOOO0,'P'8J+0C'(N;"H/,I"0JI% % Patients losing >10% BW Difference from placebo (LSMean) (95% CI) 33.9% 15.4% 22.4% 5.5% 25.4% 6.9% 18.5* (15.2;21.7 ) 16.9* (11.7;22.1) 18.5* (11.7;25.3)

4 )%'*0&'(2?('&*!>(2-%( '#;%-!#(#-!('*'&#"-%!(4%"+1&(02''(!%>+46%? M##J;6NNOOO0;"H/,I"J&'0C'(N/%%+C"CQNO/+LM#8*';;N;+L,+%+C",#8O/+LM#8*';;0M#(* M##J;6NNOOO0;"H/,I"J&'0C'(N/%%+C"CQNO/+LM#8*';;N;+L,+%+C",#8O/+LM#8*';;0M#(* 0")#+0*&"!%(:'#;%-!#<=( Do not use Saxenda : To treat Type 2 diabetes With Victoza or other GLP-1 receptor agonists Together with insulin There is no safety data on Saxenda use: With other prescription, over-the-counter, or herbal weight-loss products In people who have had pancreatitis In children <18 years of age.!2'#+%(?2)('#;%-!#<(7'@(7"5&2a#<( '#;%-!#<(?2)(4%"+1&( 02''( ( Dose of Saxenda mg daily for weight loss Evaluate patients after 16 weeks If patient has not lost 4% of baseline body weight, discontinue therapy 7"5&2A#<(?2)(&B!.( ( Dose of Victoza mg or 1.8 mg daily for diabetes!%>+46%? )C.)D#")E#/)F.+)C4)G'2,6/+4)

5 C*%'&"2-(2-(0")#+0*&"!%( :'#;%-!#<=( Which of the following patients with BMI of > 27 kg/m 2 will be eligible for Saxenda? All patients have HTN and Dyslipidemia PINK T1 DM Patient on Insulin Glargine + Insulin Aspart BLUE T1 DM Patient on 70/30 Insulin GREEN T2 DM Patient on Metformin YELLOW T2 DM Patient on Exenatide '+0&3B("-1""&2)'(#-!("&'( 52."-#&"2-'( SGLT-2 Inhibitors Empagliflozin (Jardiance ) Empagliflozin/metformin (Synjardy ) SGLT-2 Inhibitors/DPP-4 Inhibitor Empagliflozin/Linagliptin (Glyxambi ) '2!"*.3+0*52'%(52&)#-'/2)&%)3B("-1""&2)'9( +0*52'%(&)#-'/2)&#&"2-(#&(&1%(D"!-%>'( ( %./#3)%+(2*&52.%('&*!>( Aim: To determine the long-term CV safety of Empagliflozin R&+LM#.SE0-(FT/,"*UMQ;+'* V1W6)158)13 X"Q*'&GT.<"&&+;YZ0UM"&("C'#M/&"JQ951@4@@V2W623?822 Inclusion: >7000 drug-naïve patients (HbA 1c -lowering therapy (HbA 1c CV events Treatment: Randomized (1:1:1) and treated with Empagliflozin 10 mg, 25 mg, or placebo Primary outcome: Time to first occurrence of CV death, non-fatal myocardial infarction, or nonfatal stroke Zinman B, et al. N Engl J Med 2015;373(22):

6 %./#+0"?02A"-(.2!*0#&%'('%7%)#0(?#5&2)'( )%0#&%!(&2(57()"'D(!3-%"'+"2&) 4+/8#1.).3."+) %&"282"3) :5) =/"+/2%,)."2AA4+..) ) ) L+20'") M2.&+/%,)%62-#.2"3) 9,1&#.+) C4.1,24) J"'+/) ) =,B1241/2%) J>26%"28+)."/+..) F/2&)%&26) <G) <G) K/20,3&+/26+.) %./#3)%+(2*&52.% < 9( '*..#)>( Empagliflozin reduced HF hospitalization by 35% Empagliflozin reduced CV death by 38% Empagliflozin improved survival by reducing all-cause mortality by 32% M##J6NNOOO0,/`(0'&LNI'+N%B**N150157>NASFE'"175?=95 -I"J#/I%&'([,\BCCM+GS.]+,(",.Z.R",,/&.^/#"*0!+"K_";C!+;T/; HI) HH) -*.%)(-%%!%!(&2(&)%#&(:--&=(&2(/)%7%-&(2-%(!%#&1(#5)2''(0#-!.#)D(&)"#0'("-(/#&"%-&'( 4"&1(1"+1(57()"'D( %./#+0"?02A"-E0"-#+0"/&"-(:+0>;#."<=( G+(P";#"#+, 1 %'&70?Q/"&; High CV risk 5% diabetes, 26% hypertension Pre-statin era T"(+J&+* 9 %'&7Q/"&; High CV risk 38% diabetes, 46% hypertension Pre-ACEi/ARB era <29% statin S(J"L*+%*'\+, %'&@Q/"&; T2DM with high CV risk 92% hypertension >80% ACEi/ARB >75% statin J:O;GKCM;X'/P"*B"#/#M//%%+C"CQ",I;"%/#Q'% /(J"L*+%*'\+,N*+,"L*+J#+,";;/C',I8*+,/#M/&"JQ+,;BK`/C#;O+#M X9!E+,"I/bB"#/*QC',#&'**/I',(/#%'&(+, P;!;=PG*)Q;!C9D)()GBK`/C#;O/&/&",I'(+\/I#'"C'(K+,"#+','% 10 S(J"L*+%*'\+,97(LN*+,"L*+J#+,7(LV&c1@=W 90 S(J"L*+%*'\+,97(LV&c1?1W?0 S(J"L*+%*'\+,15(LV&c1?5W 70 :+,"L*+J#+,7(LV&c1@9W";"II8',#'(/#%'&(+,%'&79O//D; ?G+,P/;#+L"#'&0:",C/#122?4@??61@3@832.M##J6NNOOO0#&+"*&/;B*#;C/,#/&0'&LN;#BIQ97258?G0M#( <aUS+,P/;#+L"#'&AS,L*FE/I95554@?961?787@.M##J6NNOOO0#&+"*&/;B*#;C/,#/&0'&LN;#BIQ9>5>8 <aus0m#( HN)!/)&',\'T-.:/O+,-.U"#/*G./#"*0^'(K+,"#+','%/(J"L*+%*'\+,",I*+,"L*+J#+,";;/C',I8*+,/#M/&"JQ+, ;BK`/C#;O+#M#QJ/9I+"K/#/;+,"I/bB"#/*QC',#&'**/I',(/#%'&(+,06%/7)+)*"#/9)095174@3V@W6@3?8@2@0

7 )%'*0&'(2?(&1%('&*!>(( C*%'&"2-(2-(%./#)%+('&*!>( The EmpaREg Study demonstrated positive outcomes in all of the following CV outcomes, EXCEPT: RED BLUE GREEN YELLOW Myocardial Infarction; Stroke Heart Failure Hospitalization Cardiovascular Death All Cause Mortality

8 "2%C*"7#0%-5%9(1*.#02+(*(BFF(7'(8FF(( '#.%(!2'%G(H(&1%(720*.%( "-'*0"-(+0#)+"-%( (*3IFF(:&2*6%2<=( (( -2-"2%C*"7#0%-&(&2(+0#)+"-%(*38FF( Noninferior: similar A1c lowering More basal insulin use of Toujeo in both T1 and T2DM Rates of hypoglycemia? 1*.*0"-()( (*3JFF(D4"D/%-<( =8%2,%B,+)24)=-/2,)HRIS) Q1/%"2#4)#A)-C#+',c1M'B& 5+4()D#)Q#.+)G#48+/.2#4)&#-%/+6)"#)M2%, For patients controlled on insulin glargine U100, a higher daily dose of TOUJEO will be needed From twice-daily NPH insulin to once-daily TOUJEO, the recommended starting TOUJEO dose is 80% of the total daily NPH dosage

9 /2&%-&"#0(5#-!"!#&%'(?2)(*3JFF(1*.#-( )%+*0#)("-'*0"-( T2DM Patients with obesity/severe insulin resistance Patients requiring >200 units of insulin per day High glucocorticoid therapy Severe systemic infection Gestational diabetes with severe insulin resistance Genetic defects of insulin action Type A insulin resistance syndromes Immune mediated diabetes (anti-insulin receptor antibodies) "-'*0"-(!%+0*!%5(:&)%'"#<=(*3 BFF(#-!(*38FF(?0%;&2*51( ( "-'*0"-(!%+0*!%5(:&)%'"#<=9(%+"-('&*!"%'( Ultra long acting insulin (dosed daily) Onset of Action: minutes Its duration of action is up to 42 hours compared to 18 to 26 hours (glargine and insulin detemir) Efficacy: Non inferior to Lantus (glargine) Benefit: Flexibility in day to day dosing time d'blmg^:.<"&&+;g.r''_./#"*0[,;b*+,i/l*bi/c6'p/&p+/o'%",'p/*b*#&"*',l8 "C#+,LK";"*+,;B*+,0!+"K/#/;.aK/;+#Q",IE/#"K'*+;(0951@V17W6@51 2 &)%'"#(!2'"-+( NO dose conversion between TRESIBA U-100 or U-200 FlexTouch pens The dose window for both FlexTouch pens shows the number of insulin units to be delivered Starting Dose in Insulin Naïve T1DM Patients in insulin naïve patients with type 1 diabetes is ~ 1/3 to ½ of TDD Starting dose in insulin naïve T2DM patients is 10 units once daily

10 C*%'&"2-(2-("-'*0"-( Which of the following insulin(s) is/are bioequivalent (require no dose conversion)? RED BLUE Toujeo (Glargine) U-300 vs. Lantus (Glargine) U-100 Humalog Kwikpen U-200 vs. Humalog Kwikpen U-100 GREEN Humulin R Kwikpen U-500 vs. Humulin R U-100 YELLOW Tresiba (Insulin Degludec) U-200 vs. Tresiba U-100."-"35#'%( (/#&"%-&(#( HPI: 52-year-old woman with Type 2 DM, HTN Labs: HbA1c 8.8% Diet: None Medications Metformin (Glucophage XR) 1,000 mg bid Empagliflozin (Jardiance ) 25 mg daily Liraglutide (Victoza ) 1.8 mg daily HCTZ 25 mg once daily TS) C*%'&"2-(2-(/#&"%-&(3(#( Is this patient, AB a candidate for Saxenda? RED BLUE Saxenda (Liraglutide) is safe Use if you discontinue her Glucophage (Metformin) GREEN Use if you discontinue her Victoza (Liraglutide) YELLOW Use if you discontinue her Jardiance (Empagliflozin) D%>(&#D%(#4#>(/2"-&'( Clinical trials show 62% and 34% of patients on Saxenda (Liraglutide) 3 mg, decrease weight by 5% and 10% respectively from baseline Empagliflozin demonstrated positive CV outcomes in decreasing HF hospitalizations; CV death and all cause mortality (not MI or Stroke) PK/PD studies must demonstrate bioequivalence in order to maintain dosing in concentrated insulin with their U-100 counterparts Concentrated insulin has the same dose but less volume

11 C*%'&"2-(?2)(#*!"%-5%( On completion of this presentation, RED I learnt at least one important fact today BLUE GREEN I need one area clarified today YELLOW I slept through, so I have no questions &1#-D'K( Any questions? You can me at ameadows@umm.edu