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Pharmacotherapy for

Diabetes and Weight

Management: Update 2014
Nicole M. Quiles Alves PharmD,
M.P.H., RPh
Assistant Professor of Pharmacy

Kyle Melin, PharmD, BCPS, AE-C

Assistant Professor of Pharmacy

University of Puerto Rico School of Pharmacy

Dr. Quiles Alves is a contracted speaker for
Merck & Sharp Co.
Dr. Melin has nothing to disclose

Learning Objectives
Review existing pharmacotherapy options for diabetes
mellitus and how they benefit the patient
Discuss new therapy options for the diabetes
Review existing pharmacotherapy options for weight
loss and determine which agents may be used safely
Discuss the data regarding the use of these agents in the
diabetic patient population

Diabetes Management
Updates on New Drugs: 2014

Updates 2014: New Drugs

Abrezza (insulin human) inhalation powder

rapid inhale insulin

use in adult patients for glycemic control
MOA: stimulates peripheral glucose uptake by
skeletal muscle and fats
Not a substitute for long-acting insulin
Must be used in combination with long-acting
insulin in diabetes type 1 patients
SE: hypoglycemia, cough,throat pain, irritation

Farxiga (dapagliflozin)
Sodium glucose cotransporter type 2 (SGLT-2) inhibitor
o MOA: modulates reabsorption of glucose in the kidney, resulting in
glucose excretion in the urine

Indicated as adjunct to diet and exercise

o Oral administration, starting dose 5mg

Not to use with eGFR < 60ml/min

Take AM with or without food
SE: female genital mycotic infections, urinary tract
infections, nasopharingitis

Jardiance (empagliflozacin)
SGLP-2 inhibitor
Indicated as adjuvant with diet and exercise
Recommended dose 10mg daily with or
without food
SE: urinary tract infections, mycotic
inections in female

Tanzeum (albiglutide)
MOA: is a GLP-1 receptor agonist

Augments glucose-dependant insulin secretion and

slows gastric emptying

Indicated as an adjunct to diet and exercise

to improve glycemic control in DM Type 2
SQ injection - 30mg weekly
SE: Upper respiratory tract infection,
diarrhea, nausea, injection site reaction

Trulicity (dulaglutide)
MOA: GLP-1 receptor agonist

Increases intracellular cyclic AMP (cAMP)in beta

cells leading to glucose-dependant insulin release.
Decrease glucagon secretion and slows gastric

SQ injection, initiating dose 0.75mg weekly

SE: nausea, diarrhea, vomiting, abdominal

Xigduo XR
(dapagliflozin +metformin HCL)
MOA: SGLT-2 + metformin ER
Adjunct Tx with diet and exercise to control
glycemic control when appropriate with each
Oral tablet, 10/2,000mg recommended dose
once daily with food and titrate dose
SE: hypoglycemia, GIs symptoms

Weight Loss
2014 Update

What is significant weight loss?

Sustained loss of 5% or more generally
considered to be clinically meaningful
Initial responders tend to continue to

Initial nonresponders less likely to ever respond

If 2kg (4.4 lbs) not lost in the first 4 weeks, unlikely

to respond at all

Pharmacologic Classes
Pharmacologic strategies for weight reduction

Noradrenergic agents
GI lipase inhibition
Serotonin receptor agonists
Combination therapy
ONLY used as adjunct to comprehensive
lifestyle intervention

Noradrenergic agents
For short-term use only (12 weeks)





Schedule 2 controlled substances should

never be used for weight loss

GI lipase inhibition

Administered 3 times per day at meals

Leads to excretion of of 30% of ingested fat

Prescription strength - Xenical 120mg

OTC product - Alli 60mg
XENDOS trial

Clinical trial data for up to 4 years of use

Significant decrease in risk of developing DM-II

Serotonin receptor agonists

Lorcaserin (Belviq)

Selective serotonin 2C (5-HT2c) receptor agonist

Similar mechanism of action to fenfluramine
Data in up to 2 years of use
Significant decrease in BP, TC, LDL, and TG
Valvulopathy not statistically higher in lorcaserin
treatment group, but numerically higher
FDA requested post-approval trial
D/C at week 12 if 5% weight loss has not achieved


Combination therapy
Phentermine/Topiramate extended release
Requires titration to target doses
REMS program

MedGuide and registered provider/pharmacy

Risk of fetal malformations

D/C if 3-5% wt loss not reached in 12 weeks

Combination therapy
Naltrexone/Bupropion extended release
Requires titration to target doses
D/C if 5% decrease in weight not achieved
after 12 weeks at maintenance dosage
Pt should be opioid free for minimum of 7-10
days (14 days for buprenorphine/methadone)

Weight Loss in DM
Orlistat: XENDOS

Decreased risk of progression to DM-II

Lorcaserin: BLOOM-DM

37% achieved 5% weight loss (vs 16% for placebo)

Improved HgbA1C

Phentermine/topiramate: CONQUER trial


62% to 70% achieved 5% weight loss (vs 21% for placebo)

Decreased risk of progression to DM-II for high dose

Herbal Supplements
Look out!

High likelihood of interaction with prescription

weight loss medications

Potential for very serious adverse effects

When possible, herbal supplements should be

avoided completely while taking Rx weight loss meds

If not, provider should review individual bottles

Zoungas S, Chalmers J, Neal B, et al. Follow-up of blood-pressure lowering and glucose control in type 2 diabetes. N Engl J Med 2014; 371:1392.
Weissman PN, Carr MC, Ye J, et al. HARMONY 4: randomised clinical trial comparing once-weekly albiglutide and insulin glargine in patients with type 2 diabetes inadequately
controlled with metformin with or without sulfonylurea. Diabetologia 2014.
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002735/human_med_001735.jsp&mid=WC0b01ac058001d124 (Accessed on April 16, 2014).
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm393289.htm (Accessed on April 17, 2014).
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm415180.htm (Accessed on September 19, 2014).
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002825/smops/Positive/human_smop_000729.jsp&mid=WC0b01ac058001d127 (Accessed on
October 15, 2014).
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm403122.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery (Accessed on June 30,
Gregg EW, Li Y, Wang J, et al. Changes in diabetes-related complications in the United States, 1990-2010. N Engl J Med 2014; 370:1514.
FDA adding general warning to testosterone products about potential for venous blood clots. US Food and Drug Administration (FDA) Drug Safety and Availability. Last updated
June 25, 2014. (Available online at http://www.fda.gov/Drugs/DrugSafety/ucm401746.htm (accessed June 30, 2014)).
http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails (Accessed on June 03, 2014).

Yanovski SZ, Yanovsk JA. Long-term drug treatment for obesity: A systematic and clinical review. JAMA 2014;311(1):74-86.
Torgerson JS, Hauptman J, Boldrin MN, Sjstrm L. XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of
orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care. 2004;27(1):155-161.
Smith SR,Weissman NJ, Anderson CM, et al; Behavioral Modification and Lorcaserin for Overweight and Obesity Management (BLOOM) Study
Group. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med 2010;363(3):245-256.
Fidler MC, Sanchez M, Raether B, et al; BLOSSOM Clinical Trial Group. A one-year randomized trial of lorcaserin for weight loss in obese and
overweight adults: the BLOSSOM trial. J Clin Endocrinol Metab 2011;96(10):3067-3077.
ONeil PM, Smith SR,Weissman NJ, et al. Randomized placebo-controlled clinical trial of lorcaserin for weight loss in type 2 diabetes mellitus: the
BLOOM-DM study. Obesity (Silver Spring) 2012;20(7):1426-1436.
Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated
comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet 2011;377(9774):1341-1352.
Garvey WT, Ryan DH, Look M, et al. Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese
and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study. Am J Clin Nutr 2012;95(2):297-308.
Caixs A, Albert L, Capel I, Rigla M. Naltrexone sustained-release/bupropion sustained-release for the management of obesity: review of the data to
date. Drug Design, Development and Therapy 2014:8 14191427.