0%(( 2$6%5&7%'( · glp-1 r agonists (dm) yalbiglutide (tanzeum®) ydulaglutide...
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2$6%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
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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®)
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GLP-1: Secreted upon the ingestion of food
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Indication: Adjunct to lifestyle (reduced calorie diet and increased physical activity) for chronic weight management
In individuals with a BMI of >30 kg/m2 In individuals with a BMI of >27 kg/m2 in the presence of at least one weight-related comorbidity such as HTN, Diabetes, or Dyslipidemia
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Three 56-week, randomized, double-blind, placebo-controlled trials All patients were overweight (27-29.9 kg/m2) or obese >30 kg/m2 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)
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(Obesity/overweight + comorbidity)
Study 2 (Obesity/overweight +
Type 2 DM)
Study 3 (Obesity or overweight +
comorbidity following > 5% weight loss with diet)
Saxenda N=2487
Placebo N=1244
Saxenda N=423
Placebo N=212
Saxenda N=212
Placebo N=210
Baseline mean (SD) (kg)
106.2 (21.2) 106.2 (21.7) 105.7
(21.9) 106.5 (21.3)
100.4 (20.8)
98.7 (21.2)
% change from baseline (LSMean) -7.4 -3.0 -5.4 -1.7 -4.9 0.3
Difference from placebo (LSMean) (95% CI)
-4.5* (-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)
% Patients losing >10% BW 33.9% 15.4% 22.4% 5.5% 25.4% 6.9%
Difference from placebo (LSMean) (95% CI)
18.5* (15.2;21.7
) 16.9*
(11.7;22.1) 18.5*
(11.7;25.3)
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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.
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(Dose of Saxenda - 3.0 mg daily for weight loss Evaluate patients after 16 weeks If patient has not lost 4% of baseline body weight, discontinue therapy
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(Dose of Victoza - 1.2 mg or 1.8 mg daily for diabetes
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Which of the following patients with BMI of > 27 kg/m2 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
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SGLT-2 Inhibitors Empagliflozin (Jardiance®) Empagliflozin/metformin (Synjardy®)
SGLT-2 Inhibitors/DPP-4 Inhibitor Empagliflozin/Linagliptin (Glyxambi®)
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%./#3)%+(2*&52.%('&*!>(Aim: To determine the long-term CV safety of Empagliflozin Inclusion: >7000 drug-naïve patients (HbA1c
-lowering therapy (HbA1c 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 non-fatal stroke Zinman B, et al. N Engl J Med 2015;373(22):2117-2128
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Empagliflozin reduced CV death by 38%
Empagliflozin improved survival by reducing all-cause mortality by 32%
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High CV risk 5% diabetes, 26% hypertension
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High CV risk 38% diabetes, 46% hypertension
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The EmpaREg Study demonstrated positive outcomes in all of the following CV outcomes, EXCEPT: RED Myocardial Infarction; Stroke BLUE Heart Failure Hospitalization GREEN Cardiovascular Death YELLOW All Cause Mortality
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Noninferior: similar A1c lowering More basal insulin use of Toujeo in both T1 and T2DM Rates of hypoglycemia?
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
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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)
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Ultra long acting insulin (dosed daily) Onset of Action: 30 90 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'BLM$G^:.$<"&&+;$G.$R''$_.$/#$"*0$[,;B*+,$I/L*BI/C6$'P/&P+/O$'%$"$,'P/*$B*#&"$*',L8
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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
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Which of the following insulin(s) is/are bioequivalent (require no dose conversion)? RED Toujeo® (Glargine) U-300 vs. Lantus® (Glargine) U-100 BLUE 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
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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)
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Is this patient, AB a candidate for Saxenda®? RED Saxenda®(Liraglutide) is safe BLUE 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
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 email me at ameadows@umm.edu
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