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Glp1 clinical view
1. Role of Early Initiation of Glucagon
Like Peptide _1 Receptor (GLP_1 Agonist)
Agonist
in
Management of DM2/OBESITY
CARDIO-METABOLIC RISK REDUCTION
DR./ADEL ELNAGGAR
Endocrinologist
Dr.Erfan & Bagedo General Hospital
2. DIABETES SPOT LIGHTS
Glp_1 R Agonist
guidelines
Mechanism of
action/types/clinical outcomes
(initiation benefits)
Summary/Home message
3. :
A GROUP OF DISEASES
Characterized By High Levels Of Blood Glucose
Resulting From Defects In Insulin Production,
Insulin Action, Or Both
Diabetes Mellitus :
Metabolic Disorders
Cardio-metabolic Disorders
Complex Metabolic Disorders
Characterized By Hyperglycemia Due To An Absolute Or Relative
Lack Of Insulin
Or To A Cellular Resistance To Insulin
14. INSULIN RESISTANCE
METABOLIC SYNDROME
&
ADULT OBESITY
Central obesity (waist circumference)
IGT or IFG
High lipid profile
LDL-HDL/CHOLESTEROL/TRIGLYCERIDES
HIGH BP more than 130/90
15. Every 1% reduction in HbA1c
can reduce long-term
DIABETES COMPLICATIONS1
*p<0.0001
1. Adapted from Stratton IM et al. BMJ 2000;321:405–412.
37%
21%
14%
Microvascular
complications*
Deaths related
to diabetes*
Myocardial
infarction*
16. Benefits of weight neutral/reduction
regimens in management of
type 2 diabetes
1. Anderson and Konz. Obes Res 2001;9(Suppl. 4):326S–334S
2. Anderson et al. J Am Coll Nutr 2003;22:331–9
BP, blood pressure; CV, cardiovascular; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-
density lipoprotein cholesterol; TC, total cholesterol; TG, triglycerides
17. MANAGEMENT OF DM-2
METFORMIN
DPP4
PIOGLTAZONES
GLP1 ANALOUGES
SGLT2 INHIBITORS
SUs
INSULINs
PANCREATIC TRANSPLANTION
STEM CELLS
METABOLIC SURGERIES
Lower risk of
hypoglycemia
Higher risk of hypoglycemia
Curative
procedures
18.
19. INTERNATIONAL DIABETES FEDERATION (IDF)
2005 and 2011/12
AMERICAN GUIDELINES (ADA)
2006, 2008, 2009, 2012, 2015, 2016 ???
EUROPEAN GUIDELINES (EASD)
2006, 2008, 2009, 2012, 2015
NATIONAL GUIDELINES (KSA –EGYPT)
WE LIVE IN A WORLD OF GUIDELINES
FOR MANAGING T2DM
AACE/ACE GUIDELINES
2009, 2013, 2015
20. GUIDANCE Study 7,597 T2DM patients
Gap exists between
checking HbA1c and achieving target HbA1c <7%
Stone MA et al. Diabetes Care. 2013 ; 36: 2628-38
Percent
21. Barriers to Diabetes Care
Clinical Practice
Therapeutic Regimen
(poly-pharmacy/complex)
Disease Process
Patient Adherence
23. INCRETINS
Incretins are gut-derived hormones,
released in response food intake (mainly
glucose and fat).
They exert a wide range of effects,
including stimulation of pancreatic
insulin secretion in a glucose-dependent
manner and play an important role in the
local gastrointestinal and whole-body
physiology
24. Two gut-hormones were found to
mediate the “incretin effect”
Glucagon Like Peptide _1 (GLP-1)
secreted from the K-cells in the
duodenum and jejunum
Glucose-dependent Insulinotropic
Polypeptide (GIP)
secreted from the L-cells of the
distal ileum and colon and
34. Types Of Glp_1 Agonists
Exenatide
short acting twice daily
Liraglutide:
Another GLP-1 analog with longer half-life,
similar to exenatide with once-daily injection.
Diabetes Care. 2007;30:1608-1610
Long acting exenatide:
Highly effective with once weekly injection.
Diabetes Care. 2007;30:1487-1493
Incretin mimetics
35. Exenatide
• The first incretin-related therapy
available for patients with type 2
diabetes.
• Naturally occurring peptide from the
saliva of the Gila Monster.
• Has an approximate 50% amino acid
similar with GLP-1.
• Binds to GLP-1 receptors and behaves
as GLP-1.
37. Incretin mimetics
Exenatide
• Resistant to DPP-4 inactivation.
Following injection,
• it is measurably present in plasma
for up to 10 hours.
• Suitable for twice a day
administration by subcutaneous
injection.
Regul Pept. 2004;117:77-88.
Am J Health Syst Pharm. 2005;62:173-181.
38. Nausea With
Exenatide
• was seen uniformly across the
clinical trials, although most
episodes were mild-to-moderate in
intensity and generally intermittent.
• more frequent at the initiation of
treatment and decreased over the
course of several weeks.