GLP-1 Analogs and Lifestyle
Modifications
MARGARITA SIANOSYAN, DOCTOR OF PHARMACY
CANDIDATE, LECOM COLLEGE OF PHARMACY
Overview
 GLP-1 analog’s role in the body
 Available GLP-1 analogs on the market
 Advantages over other anti-diabetic agents
 Benefits when combined with lifestyle modifications
 Importance of healthy diet, physical activity, and
sleep with GLP-1 analogs
 Nutrition and physical activity recommendations
GLP-1 in Type 2 Diabetes
Ganda, Om. Diabetes and the GI Tract: Important Interrelationship. Medscape reference. WebMD 2011.
GLP-1 Analogs
 Synthetic and structurally-altered version of naturally
produced hormone

Mimic physiological actions of GLP-1
 Naturally produced GLP-1 are rapidly inactivated by
(dipeptidyl-peptidase 4) DPP-4 enzyme

Half life is 1-2 minutes
 GLP-1 analogs are resistant to inactivation by DPP-4
enzyme and stay longer in the body
 Work only in presence of glucose
Dungan K. Glucagon-like peptide-1-based therapies for the treatment of type 2 diabetes mellitus. In: UpToDate, Nathan, DM (Ed), UpToDate, Waltham, MA 2012.
Mechanisms of Action
 Glucose-dependent insulin





production
Stimulates beta-cells and
causes insulin secretion
Inhibits glucagon secretion
Delays gastric emptying
Induces satiety and
decreases food intake
Improves beta-cell function
and proliferation (animal
studies)
Conetta C, Patel, M. (2012, February 22). GLP-1 Analogs and DeFronzo's Octet. Diabetes in Control.
Retrieved September 5, 2012, from http://www.diabetesincontrol.com/articles/features/12372
http://www.socbdr.org/e4/e887/volRdsVolumes5237/issRdsIssues5874/chpRdsChapters5886/strRdsArticles5887/
index_en.html?preview=preview&showfulltext=1
Satiety and Food Intake
 Long term weight loss
 Exact mechanism is unclear
 Acts on hypothalamic feeding centers
Conetta C, Patel, M. (2012, February 22). GLP-1 Analogs and
DeFronzo's Octet. Diabetes in Control. Retrieved September 5, 2012,
from http://www.diabetesincontrol.com/articles/features/12372
http://www.funderstanding.com/educators/brain-anatomy/
GLP-1 Analogs on the Market
 Used as an adjunct to diet and exercise to improve




glycemic control
Administered by subcutaneous injection
Byetta (Exenatide) – twice daily SQ injection
Victoza (Liraglutide) – once daily SQ injection
Bydureon (extended-release Exenatide) – once
weekly SQ injection
Dungan K. Glucagon-like peptide-1-based therapies for the treatment of type 2 diabetes mellitus. In: UpToDate, Nathan, DM (Ed), UpToDate, Waltham, MA 2012.
Safety Profile
 Mild or moderate nausea
 Titrating dose may limit nausea
 Diarrhea
 Headaches
 Dizziness
 Hypoglycemia when taken with sulfonylureas
 Rare cases of acute pancreatitis and renal dysfunction
 Exenatide should not be used in patients with
creatinine clearance <30 mL/min
McCulloch DK, Munshi M. Treatment of type 2 diabetes mellitus in the elderly patient. In UptoDate, Nathan DM, Schmader KE (Ed), UpToDate, Waltha, MA.2012.
http://www.uptodate.com/contents/treatment-of-type-2-diabetes-mellitus-in-the-elderly-patient
GLP-1 with other Anti-diabetics
 Can be used alone or in
combination with other
anti-diabetic agents
 Combination with
dipeptidyl-peptidase-4
(DPP-4) inhibitors is not
recommended and is not
FDA approved
Hester, SA. Pharmacist’s Letter. Combining a GLP-1 Agonist and a DPP-4
Inhibitor for Type 2 Diabetes. Stockton, CA: Therapeutic Research
Faculty; [online] http://www.pharmacistsletter.com. September 5, 2012.
http://www.ehow.com/how_7433049_use-byetta-pen.html
In Comparison to Other Anti-diabetics
 Less incidence of
hypoglycemia
 Greater reduction in A1C
levels
 Weight reduction
 Undesirable effects of other
anti-diabetic agents can
lead to non-adherence to
medications
Diabetes Obes Metab. (2012, April 9). GLP-1 a Good Choice for
Glycemic Control?. Diabetes in Control. Retrieved September 5, 2012,
from http://www.diabetesincontrol.com/articles/53-diabetesnews/12658-glp-1-a-good-choice-for-glycemic-control
http://www.freediabetestestsupplies.com/cinnamon-diabetes-naturalcure/
Cardiovascular Health
 Primary cause of death in Type 2 Diabetes patients
is cardiovascular disease (CVD)
 GLP-1 agonists lower blood pressure and cholesterol
 Increased cardiac contractility and protection
against ischemia
Spellman CW. (2010). Pharmacology of GLP-1 Agonists: Describing the Therapeutic Potential to Patients. The Journal of the American Osteopathic Association, 11(2), eS10-eS14. Retrieved
September 5, 2012 from http://www.jaoa.org/content/111/2_suppl_1/eS10.full
http://www.virtua.org/health/cardiovascular-health.aspx
Adjunct to Diet and Weight Control
 Works best when
combined with healthy
diet and physical activity
 Diet and weight control


Slows progression to Type 2
diabetes
Prevents complications
Conetta C, Patel, M. (2012, February 22). GLP-1 Analogs and DeFronzo's Octet. Diabetes in
Control. Retrieved September 5, 2012, from
http://www.diabetesincontrol.com/articles/features/12372
http://www.northcentraliaredcross.org/wp-content/uploads/2012/03/Healthy-Foods_C.gif
Medical Nutrition Therapy (MNT)
 “Nutritional diagnostic, therapy, and counseling
services for the purpose of disease management,
which are furnished by a registered dietitian or
nutrition professional.”
 Key component in preventing diabetes, managing
diabetes, and preventing associated complications
 Covered by Medicare and many other private and
state insurance plans
American Diabetes Association. Medical Nutrition Therapy: A Key to Diabetes Management and Prevention-2010. Clinical Diabetes. 2010;28:12-18
Medical Nutrition Therapy (MNT)
 Current literature supports
MNT as an effective method
for treating diabetes
 18 studies reviewed by ADA


8 were randomized controlled trials
Intervention groups had greater
improvements in A1C levels and
fasting plasma glucose
 Lifestyle modifications play an
important role in managing
diabetes
American Diabetes Association. Medical Nutrition Therapy: A Key to Diabetes
Management and Prevention-2010. Clinical Diabetes. 2010;28:12-18
http://www.cvmc.org/hospital/departments-services/patient-supportservices/nutrition-diabetes-counseling
Diet
 Important to reinforce healthy
diet
 Types of foods

Limiting foods high in sugar, salt,
and fat
 Frequency
 Eating smaller portions throughout
the day
 Portion control
 Keeping track of carbohydrate intake
American Diabetes Association. Medical Nutrition Therapy: A Key to
Diabetes Management and Prevention-2010. Clinical Diabetes.
2010;28:12-18
http://www.saintshealthymarriages.com/healthy-diet-plans/
Nutrition
 Complex carbohydrates
(55%), protein (20%),
healthy fats (25%)
 High fiber
carbohydrate foods
 Saturated fat intake of
<7% of total calories
 Minimal trans fat
intake
American Diabetes Association. Medical Nutrition Therapy: A Key to Diabetes Management and
Prevention-2010. Clinical Diabetes. 2010;28:12-18
http://concordweightloss.com/2011/05/03/downsize-portions-for-better-weight-control/
Physical Activity
 At least 150 minutes per
week of moderate-intensity
aerobic physical activity

50-70% of maximum heart rate
 Resistance training three
times a week
American Diabetes Association. Medical Nutrition Therapy: A
Key to Diabetes Management and Prevention-2010. Clinical
Diabetes. 2010;28:12-18
http://extrachapter.com/exercise-and-diabetes/
Weight Control
 Even small amounts of
weight loss can improve
glycemic control
 Changes in BMI can reduce
A1C and blood pressure
 Improve lipid levels
 Reduce cardiovascular risk
factors
American Diabetes Association. Weight Loss, Glycemic Control, and Changes in
Cardiovascular Biomarkers in Patients With Type 2 Diabetes Receiving Incretin
Therapies or Insulin in a Large Cohort Database-2010. Diabetes Care. 2010;
33:1759-1765.
http://www.askcms.com/weight-loss/natural-weight-loss-supplements/
Sleep
 In addition to healthy diet
and exercise, sleep also
has an important role in
weight control
 Study found that middleaged, overweight men who
slept 8.5 hours burned
more fat than patients that
slept 5.5 hours
 Elevated levels of ghrelin
in the blood
Ann Intern Med. 2010;153:435-441, 475-476
www.adultspancounseling.com/wp-content/uploads/2008/04/ManSleeping.jpg
Conclusion
 GLP-1 analogs have several mechanisms of action in
the body.
 GLP-1 analogs’ advantages over other anti-diabetic
agents include less hypoglycemia, better A1C control,
no weight gain, and cardioprotection.
 GLP-1 analog therapy is used as an adjunct to healthy
diet and exercise.
 Healthy lifestyle modifications are necessary for
successful treatment.