The GLP1-RA Class of Medications -...
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Beyond A1C Non-glycemic Effects of GLP-1 Receptor Agonists Olga Astapova MD, PhD Luis Chavez MD URMC Endocrinology Fellows
Transcript of The GLP1-RA Class of Medications -...
Beyond A1CNon-glycemic Effects of GLP-1 Receptor Agonists
Olga Astapova MD, PhDLuis Chavez MDURMC Endocrinology Fellows
Disclosures
› No conflicts of interest.
Learning Objectives
1. Understand the physiological role of our gut hormones in glucagon inhibition, glucose dependent insulin secretion, appetite regulation and gastric motility.
2. Understand the effectiveness of this class of medication to reduce hyperglycemia and weight.
3. Learn about cardiovascular benefits of GLP1 receptor agonists.
4. Become familiar with adverse effects and cost of GLP1 receptor agonists.
Diabetes Treatment Goals
Avoiding imminent death
Alleviating symptoms of hyperglycemia
Preventing complications
1920s
Insulin
1950s
Tolbutamide
2000s
FraminghamDCCT / EDICUKPDS
FingerstickBG metersHemoglobin A1C
1970s
JAMA. 2015;314(1):52-60;2. World Heart Federation. Cardiovascular disease risk factors
Action to Control Cardiovascular Risk in Diabetes (ACCORD)
HbA1C 6.4%
HbA1C 7.5%
N Engl J Med 2008; 358:2545-2559
“Sponsors should establish an independent cardiovascular endpoints committee to prospectively adjudicate, in a blinded fashion, cardiovascular events during all phase 2 and phase 3 trials.”
GLP1 Receptor Agonists
Saraiva and Sposito Cardiovascular Diabetology 2014, 13:142
Albèr et al. Diabetes Obes Metab. 2017 Jul;19(7):915-925
Exenatide (Byetta)
Lixisenatide (Adlyxin)
Liraglutide (Victoza)
Albiglutide (Tanzeum)
Dulaglutide (Trulicity)
Semaglutide (Ozempic)Insulin ↑
Among patients with T2DM at increased risk for CV events, does daily liraglutide reduce CV mortality, nonfatal MI, or nonfatal strokes when compared to placebo?
LEA
DER
N Engl J Med 2016; 375:311-322
9340 patients
≥ 50 years old
Type 2 diabetes
Mean 12.8 years diabetes duration
Mean HbA1C 8.7%
High CV risk: > 70% had CV disease
Placebo
(plus standard care)
Liraglutide
(plus standard care)
Hemoglobin A1C and Weight ReductionLE
AD
ER
WEIGHT2.3 KG
N Engl J Med 2016; 375:311-322
LEA
DER
13.0%
14.9%
Primary Composite Outcome❑cardiovascular death❑nonfatal myocardial infarction❑nonfatal stroke
N Engl J Med 2016; 375:311-322
Renal BenefitLE
AD
ER
N Engl J Med 2016; 375:311-322
LEA
DER
Adverse Events
N Engl J Med 2016; 375:311-322
LEA
DER
Adverse Events
N Engl J Med 2016; 375:311-322
LEA
DER
Adverse Events
N Engl J Med 2016; 375:311-322
LEA
DER
Adverse Events
N Engl J Med 2016; 375:311-322
Among patients with T2DM at increased risk for CV events, does daily liraglutide reduce CV mortality, nonfatal MI, or nonfatal strokes when compared to placebo?
LEA
DER
YES
N Engl J Med 2016; 375:311-322
Albèr et al. Diabetes Obes Metab. 2017 Jul;19(7):915-925
Exenatide (Byetta)
Lixisenatide (Adlyxin)
Liraglutide (Victoza)
Albiglutide (Tanzeum)
Dulaglutide (Trulicity)
Semaglutide (Ozempic)
In patients with type 2 DM at high CV risk, is semaglutidenon-inferior to placebo in terms of CV safety?
SUST
AIN
-6
3297 patients
Mean age: 65
Type 2 diabetes
Mean 13.9 years diabetes duration
Mean HbA1C 8.7%
60% ischemic heart disease
93% hypertension
Placebo
(plus standard care)
Semaglutide
(plus standard care)
N Engl J Med 2016; 375:1834-1844
High CV risk
Hemoglobin A1C ReductionSU
STA
IN-6
N Engl J Med 2016; 375:1834-1844
Weight ReductionSU
STA
IN-6
N Engl J Med 2016; 375:1834-1844
Primary Composite Outcome
6.6%
8.9%
N Engl J Med 2016; 375:1834-1844
❑cardiovascular death❑nonfatal myocardial infarction❑nonfatal stroke
SUST
AIN
-6
Adverse EventsSU
STA
IN-6
N Engl J Med 2016; 375:1834-1844
In patients with type 2 DM at high CV risk, semaglutide is superior to placebo in terms of CV safety.
SUST
AIN
-6
Lancet Diabetes Endocrinol. 2018 Feb;6(2):105-113
GLP-1 Receptor Agonists: CV Outcomes Compared with Placebo
LixisenatideLiraglutide
SemaglutideExenatide
LixisenatideLiraglutide
SemaglutideExenatide
Ongoing Clinical Trials
Ther Adv Chronic Dis 2018, Vol. 9(1) 33–50
GLP1 Receptor Agonists Decision Making
PROS CONS
↓ HbA1C Nausea
↓ Weight Heart burn
↓ Cardiovascular events Gallstones
↓ Overall mortality Cost
Take Home Points
› Fundamental paradigm shift in T2D management.
› Several classes of glucose lowering medications improve CV outcomes in RCTs.
› These emerging data should shift focus of T2D Rx from A1C alone to comprehensive CV risk reduction.
We now have options to treat T2DM that have beneficial
outcomes beyond A1C reduction.
~ Your friendly neighborhood endocrinology fellows ~
