beyond metformin dr clayton feb 22

Dr. Dale Clayton, MD, FRCPC, Endocrinologist, RCH

Beyond Metformin, Navigating The Treatment Continuum For Your Patients With Type 2 Diabetes

Faculty/Presenter Disclosure

Faculty: Dr Dale Clayton

Relationships with commercial interests: Grants/Research Support: none Speakers Bureau/Honoraria: Animas, Boehringer

Ingelheim, Lilly, Medtronic, Novo Nordisk, Sanofi Aventis Consulting Fees: None Other: Staff Endocrinologist-Fraser Health, Clinical

Assistant Professor-UBC Medicine

Disclosure of Commercial Support

This program has received financial support from Novo Nordisk Canada Inc. in the form of an unrestricted educational grant

Potential for conflict(s) of interest: Dr Clayton has received financial support/ honorariums from the

companies listed in the disclosures whose products are discussed in the program, including: Eli Lilly Canada Inc.: insulin lispro sanofi-aventis Canada Inc.: insulin glargine, insulin glulisine

Novo Nordisk Canada Inc. distributes products that will be discussed in this program: Victoza, Levemir and Novo Rapid

Mitigating Potential Bias

Bias in this program has been mitigated using independent content validation as follows:

All content has been reviewed by a physician steering committee, pharmacist expert reviewers, and the College of Family Physicians Canada

All data has been sourced from evidence that is clinically accepted

All support used in justification of patient care recommendations conform to generally accepted standards and CDA guidelines

Steering Committee

Dr. Breay Paty (Endocrinologist)

Dr. William Harvey (Family Physician) Dr. Orly Hermon (Family Physician) Dr. Gihane Zarifa (Family Physician) Dr. Mulluvila R.K. Suresh (Family Physician)

Robert Roscoe (Pharmacist) Pascale Therrien (Pharmacist)

Today’s Objectives

By the end of this program, attendees will be able to:

Recognize the rationale for timely initiation and intensification of treatment to achieve glycemic targets

Understand how currently available treatment options compare with respect to key challenges in diabetes management: A1C, weight and hypoglycemia

Implement effective strategies to help patients and health practitioners overcome barriers to treatment at various stages of the treatment continuum

Recognize importance of establishing individualized targets (i.e., A1C, weight) based on patient characteristics

Case Study: Meet Jason

47 years old Factory worker – works shifts Private insurance coverage Married Non-smoker Relies on fast-food during

late shifts Mother had type 2 diabetes Willing to change lifestyle to

treat diabetes

Image of Jason

Jason has just been diagnosed with type 2 diabetes

Jason has just been diagnosed with type 2 diabetes

Jason47 years old

Jason: At diagnosis

Diabetes duration

Newly diagnosed

Height 176 cm

Weight 93 kg

BMI 30 kg/m2

Waist circumference

110 cm

A1C 8.7%

FPG 10.5 mmol/L

PPG 11.2 mmol/L

Blood pressure 126/75 mm Hg

eGFR 95 ml/min

A1C testing can occur every 6 months in adults during periods of treatment and lifestyle stability when glycemic targets have been consistently achieved

1. CDA. Can J Diabetes. 2013;37(suppl 1):S1-S212.

Establishing individualized glycemic targets

- Limited life expectancy

- Functional dependency

- Extensive CVD and high risk of ischemic events

- Multiple co-morbidities

- Recurrent severe hypoglycemia

- Longstanding diabetes and difficulty achieving A1C ≤7% despite therapy

Most patients with type 2 diabetes

To further lower risk of nephropathy and retinopathy (must be balanced against the risk of hypoglycemia)

A1C should be tested every 3 months in most individuals

Unless contraindicated, metformin is the initial antihyperglycemic agent of choice.


oror

Jason: Initial diagnosis

Jason’s A1C at diagnosis was 8.7% He started:

Attending diabetes education classes Avoiding fast-food Going for walks with his wife Initiated metformin 500 mg BID

After 2 weeks metformin was increased to 1000 mg BID as tolerated

Jason: 3 months

After 3 months of treatment Jason’s A1C is still not at his target

He has not experienced any hypoglycemic events but is worried because his meal time varies depending on his shifts

Diabetes duration

3 months

Weight 91 kg

BMI 29.4 kg/m2

Waist circumference

108 cm

A1C 7.8%

FPG 8.9 mmol/L

PPG 9.0 mmol/L

Current treatment

Lifestyle interventionMetformin (1000 mg BID)


Relative risk reduction

1. Stratton IM et al. BMJ 2000;321:405-412.

Early A1C reductions have important benefits

Diabetes-relate

d

endpoints

19%

Cataract

extracti

on

21%

Diabetes-relate

d

mortality

14%

All-cause

mortality

14%

Fatal/n

on-fatal

MI

12%

Fatal/n

on-fatal s

troke

37%

Microvasc

ular

endpoints

43%

Amputation/death

from PVD

16%

Heart failu

re

21%

A1C

What can a

1%A1C reduction

can do for your patients?

Legacy Effect: Early and aggressive control has long-term benefits

Any diabetes- related endpoint

Myocardial infarction

All-cause mortality

* At the end of post-trial follow-up (median 8.5 years). † Significant reduction on intensive therapy vs. conventional therapy.1. Holman et al. NEJM. 2008;359:1577-89.

9%†

15%† 13%

†reduced relative risk

Microvascular disease

24%†

reduced relative risk



The positive effect of early and intensive glucose control

Considerations in treatment selection to help patients achieve individualized targets

Degree of hyperglycemia

Risk of hypoglycemia

Overweight or obese

Comorbidities (renal, cardiac hepatic)

Preferences and access to treatment (administration considerations)

BG lowering efficacy and durability

Risk of hypoglycemia

Effect on weight

Contraindications/side effects

Cost and coverage

Patient Characteristics Agent Characteristics


A1C

kg

hypo

Hypoglycemia can be a silent burden for your patients

Hypoglycemia has been associated with:1,2 Reduced quality of life Reduced quantity and quality of sleep Impaired ability to drive Negative effects on interpersonal relationships Increased cardiovascular morbidity and mortality

85%85%of type 2 diabetes patients DO NOT REPORT mild/moderate hypoglycemia to their doctors3

1. Seaquist et al. Diabetes Care 2013;36:1384-1395. 2. CDA. Can J Diabetes. 2013;37(suppl 1):S1-S212. 3. Leiter, Yale et al. Can J Diabetes 2005; 29(3): 186-92.

hypo

BMI=Body Mass Index; 1. CDA. Can J Diabetes. 2013;37(suppl 1):S1-S212.

5%5%toto

10%10%

Greater BMI is associated with poorer quality of lifeGreater BMI is associated with poorer quality of life

Avoidance of weight gain is important in type 2 diabetes

Glycemic Glycemic controlcontrol

Insulin Insulin sensitivitysensitivity

Lipid Lipid controlcontrol

Blood Blood pressure pressure controlcontrol

kg

Relative A1C lowering

Change in body weight

Overall risk of hypoglycemia

Cost

Alpha glucosidase inhibitor (acarbose)

Neutral to Rare $$

DPP-4 inhibitors Neutral to Rare $$$

GLP-1 receptor agonists to Rare $$$$

Insulin Yes $-$$$$

Meglitinides Yes $$

Sulfonylureas Yes $

TZDs Rare $$

Weight loss agent (orlistat)

None $$$

A1C kg hypo

What is important to your patient?

TZDs=thiazolidinediones; AGIs=alpha-glucosidase inhibnitors; GLP-1=glucagon-like Peptide 1; DPP-4=dipeptidyl peptidase-4. 1. CDA. Can J Diabetes. 2013;37(suppl 1):S1-S212.

Comparing antihyperglycemic agents




• Improved postprandial control, GI side effects

DPP-4 inhibitors

• GI side effectsGLP-1 receptor agonists

Insulin • No dose ceiling, flexible regimens

Meglitinides • Less hypoglycemia in context of missed meals but usually requires TID to QID dosing

Sulfonylureas • Gliclazide and glimepiride associated with less hypoglycemia than glyburide

TZDs • CHF, edema, fractures, rare bladder cancer (pioglitazone), cardiovascular controversy (rosiglitazone), 6-12 weeks required for maximal effect

Weight loss agent (orlistat) • GI side effects

What is important to your patient?

Discuss: Jason’s treatment options

Jason’s A1C is above his target

He works shifts and it is hard for him to stick to a meal schedule

He is concerned about hypoglycemic events

What agent would you choose for Jason?

Diabetes duration 3 months

Weight 91 kg

BMI 29.4 kg/m2

Waist circumference 108 cm

A1C 7.8%

FPG 8.9 mmol/L

PPG 9.0 mmol/L

Current treatment Lifestyle interventionMetformin (1000 mg BID)

Consider: A1C kg hypo

Jason: 6 months

After 3 months on your chosen treatment Jason’s A1C is at target

He maintains an active lifestyle and feels motivated to continue after recent weight loss

Diabetes duration

6 months

Weight 85 kg

BMI 27.8 kg/m2

Waist circumference

100 cm

A1C <7.0%

FPG 6.8 mmol/L

PPG 8.5 mmol/L

Current treatment

Lifestyle interventionMetformin (1000 mg BID)Your Treatment Choice

Jason: 5 years

Over the years Jason’s diabetes has progressed and modifications to treatment have been made

Recently, he has missed a few checkups and his A1C is above target

Diabetes duration

5 years

Weight 87 kg

BMI 28.4 kg/m2

Waist circumference

105 cm

A1C 8.1%

FPG 8.4 mmol/L

PPG 10.0 mmol/L

Current treatment

Lifestyle interventionMetformin (1000 mg BID)Your Treatment Choice


Relative A1C lowering

Change in body weight

Overall risk of hypoglycemia

Cost


Neutral to Rare $$

DPP-4 inhibitors Neutral to Rare $$$

GLP-1 receptor agonists to Rare $$$$

Insulin Yes $-$$$$

Meglitinides Yes $$

Sulfonylureas Yes $

TZDs Rare $$

Weight loss agent (orlistat)

None $$$

After 2 agents, what next?



A1C kg hypo

Survey

I prefer to delay insulin until it is absolutely necessary

of physicians delayed insulin therapy until absolutely necessary

Peyrot et al. Diabetes Care. 2005;28:2673-2679.

Delay of oral

medication initiation was the

strongest correlate of insulin therapy delay

1 2 3 4 5 6

Fully Disagre

e

Disagree

Somewhat

Disagree

Somewhat Agree

Agree Fully Agree

Insulin initiation is improving, but targets are still not being met

Canadian physicians completed a survey about type 2 diabetes patients

87% of type 2 diabetes patients were prescribed antihyperglycemic agents. Of those:

19% were on insulin only

42% were on insulin + AHA agent

Only 50% of patients met A1C ≤7.0%

Leiter et al. Can J Diabetes. 2013;37:82-89.

Choose a basal insulin

Jason’s A1C is above target (≤ 7.0%)

Shift work increases his risk of hypoglycemia

He continues to struggle with his weight

Insulin detemir or glargine (long-acting analogues) instead of NPH to reduce the risk of nocturnal and symptomatic hypoglycemia

Weight gain:Detemir < Glargine & NPH

Patient Characteristics Consider

1. CDA. Can J Diabetes. 2013;37(suppl 1):S1-S212. 2.Levemir product Monograph. Novo Nordisk Canada: 2011. 3. Lantus Product Monograph. sanofi-aventis Canada Inc. 2012.

A1C

kg

hypo

1. Adapted from Nasrallah SN et al. Clinical Medical Insights: Endocrinology and Metabolism 2012;5:31-7; 2. T. Heise, et al. Diabetes 2004. 3. CDA. Can J Diabetes. 2013;37(suppl 1):S1-S212.

A closer look at the basal insulins...

Duration1 Variability2

NPH Up to 18 hours 68% • Greatest risk for hypoglycemia1

Detemir 16-24 hours 27% • Lower hypoglycemia risk3

Glargine 24 hours 48% • Lower hypoglycemia risk3

Insulin analogues are associated with a less pronounced peak versus NPH insulin.

Insulin analogues are associated with a less pronounced peak versus NPH insulin.

When initiating basal insulin consider:

Minimize hypoglycemia

• Remind patient about signs and symptoms of hypoglycemia, and what to do (consider handout)

Titration • Teach patient how to adjust insulin dose

Injection • Demonstrate the 1st injection in your office

hypo

7.0 mmol/

L

Weight • Re-communicate the importance of weight management

• Consider choosing an insulin that minimizes weight gain

kg


Other considerations when starting insulin

With the exception of TZDs which should not be combined with insulin

Antihyperglycemic agents can be combined with basal insulin

There is no maximum dose of insulin - Adjust to glucose target & minimize hypoglycemia


What to do with other therapies?

Remember

Jason: Starting on a basal insulin analogue

Jason begins using 10 units of basal insulin analogue He continues taking his current medications

He is instructed to titrate 1 unit every night until his FPG is 4 - 7 mmol/L He records his blood glucose levels before breakfast and

before bed

His doctor reminds him of the symptoms of hypoglycemia and provides a handout of instructions Oral antihyperglycemic agents may need to be reduced if

daytime hypoglycemia occurs

Jason’s first week

Jason’s Logbook: Representative of the previous week

8.4 mmol/L

8.4 mmol/L

8.4 mmol/L

8.3 mmol/L

10 units

12 units

8.3 mmol/L

8.2 mmol/L

8.2 mmol/L

13 units

11 units

14 units

15 units

16 units

Jason will continue to titrate insulin dose until he reaches his target FPG

Jason: 3 months on basal insulin analogue

Jason has reached his A1C target with 20 units of insulin

Diabetes duration

5 years

Weight 87 kg

BMI 28.4 kg/m2

Waist circumference

105 cm

A1C <7.0%

FPG 6.2 mmol/L

PPG 8.9 mmol/L

Current treatment

Lifestyle interventionMetformin (1000 mg BID)Your Treatment ChoiceBasal insulin analogue (20 units)

Jason can maintain this dose as long as his A1C

target is met

Jason can maintain this dose as long as his A1C

target is met

Key Takeaways

A1C reduction

Weight

Hypoglycemia

Individualization of targets and treatment

Timely initiation & intensification

Coverage

When considering type 2 diabetes treatment consider:

A1C

kg

hypo $

Today’s Objectives

Now we can:

Recognize the rationale for timely initiation and intensification of treatment to achieve glycemic targets

Understand how currently available treatment options compare with respect to key challenges in diabetes management: A1C, weight and hypoglycemia

Implement effective strategies to help patients and health practitioners overcome barriers to treatment at various stages of the treatment continuum

Recognize importance of establishing individualized targets (i.e., A1C, weight) based on patient characteristics

FAQsFAQs

When & how to intensify insulin after basal insulin is initiated.

How to help patients overcome injection barrier.

Is there a cardiovascular risk with incretin therapies?

Is there a pancreatitis risk with incretin therapies?

Case examples - What would you consider for a patient with:

Renal impairment for whom you are considering an incretin therapy Long-standing diabetes and high blood pressure currently on basal insulin Slightly elevated A1C currently on MET Long-standing diabetes on triple therapy of MET + SU + DPP-4 inhibitor Experiencing hypoglycemic episodes on MET + NPH Combining insulin and incretin

Reminder: Diabetes is progressive

IFG=impaired fasting glucose; IGT=impaired glucose tolerance.

Kendall DM et al. Am J Med. 2009;122(6)(suppl 6A):S37-S50.

Insulin intensification: Add mealtime insulin to maintain A1C targets

If A1C >7%, FPG ≤7 mmol/L, add rapid-acting insulin analogue (RAIA) to basal insulin

RAIA: Rapid-acting insulin analogue; PPG: postprandial plasma glucose1. Meneghini et al. Endocr Pract. 2011;17(5):727-36.

START WITH 1 MEALRAIA can provide effective control when added just prior to a

meal, with basal insulin.

Choose the meal that is most convenient for the patient.

START WITH 4 UNITSThe pre-meal blood glucose at the meal following dosing (or

the 2-hour PPG) can be used to titrate the dose for the next day.

Choose the method that is most convenient for the patient.

Algorithm for adding mealtime insulin

Jenny injects 26 units of basal insulin and has an FPG that is regularly <7mmol/L.

To reduce her PPG to target Jenny injects 4 units of insulin just before lunch, as instructed by her doctor.

She then tests her blood sugar just before her bedtime and records the result in her dose diary.

An example of mealtime insulin monitoring and dose adjustment

She has been instructed to add 1 unit of

mealtime insulin per day until next pre-meal

glucose is between 4-7 mmol/L

FAQsFAQs







COMMUNICATE

• Inform patient that currently available needles are very short/thin

• Explain the advantages of achieving target glucose levels

• Work with your patients diabetes healthcare team to address any of your patients concerns

Funnell M. Clinical Diabetes 2007; 25(1):36-8. FIT Forum for Injection Technique Canada: Recommendations for Best Practice in Injection Technique. 2012; 1-28.

EVALUATE

• Consider whether injection is a patient vs. physician barrier

Useful consideration in overcoming potential injection barriers

Needle used for

intravenous blood draw (i.e., A1C

test)20G

Needle used for

intramuscular

vaccination (i.e., flu shot) 23G

Needle used with GLP-1 RA or insulin

32G

Width of two hairs

DEMONSTRATE

• Administer the first injection in-clinic

• Many educators perform a dry injection on themselves in the presence of the patient

FAQsFAQs







R

1. Johansen O-E., et al. Cardiovascular Diabetology. 2011;11:3;doi:10.1186/1475-2840-11-3. 2. Frederich R, et al. Postgrad Med. 2010;122(3):16–27. 3. Williams-Herman D, et al. BMC Endocr Disord. 2010;10:7. 4. Ratner R, et al. Cardiovascular Diabetology. 2011;10:22. 5. www.fda.gov/ohrms/dockets/ac/09/briefing/2009-4422b2-01-FDA.pdf -

Accessed Sept. 23, 2011.

Incretin agent better Comparator better10.50.250.125 2 4 8

Sitagliptin3

N=10,246

Saxagliptin2

N=4,607

0.680.68

0.430.43

0.160.16 0.740.74

0.410.41 1.121.12

0.230.23 0.800.80

Exenatide4

N=3,945 0.70.70.380.38 1.311.31

Liraglutide5

N=6,638 0.630.630.320.32 1.241.24

Linagliptin1

N=5,239 0.340.34

No increased risk of CV events observed with

incretin therapies

Is there an increased risk of CV events with incretin therapies?

FDA upper bound 95% criterion for approvability

R

*Exenatide once weekly is not approved or available in Canada. All found on www.clinicaltrials.gov. 1. Clinicaltrials.gov identifier: NCT01243424 2. Clinicaltrials.gov identifier: NCT01107886 3. Clinicaltrials.gov identifier: NCT00790205 4. Clinicaltrials.gov identifier:

NCT01144338 5. Clinicaltrials.gov identifier: NCT01144338

DPP-4 INHIBITORSDPP-4 INHIBITORS Completion DateCompletion Date

Linagliptin1CAROLINA: Cardiovascular Outcome Study of Linagliptin Versus Glimepiride in Patients With Type 2 Diabetes

September 2018

Saxagliptin2SAVOR-TIMI 53: Does Saxagliptin Reduce the Risk of Cardiovascular Events When Used Alone or Added to Other Diabetes Medications

July 2013

Sitagliptin3 TECOS: Sitagliptin Cardiovascular Outcome Study

December 2014

GLP-1 RECEPTOR AGONISTSGLP-1 RECEPTOR AGONISTS Completion DateCompletion Date

Exenatide4

EXSCEL*:Exenatide Study of Cardiovascular Event Lowering Trial A Trial To Evaluate Cardiovascular Outcomes After Treatment With Exenatide Once Weekly In Patients With Type 2 Diabetes Mellitus

March 2017

Liraglutide5LEADER: Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results - A Long Term Evaluation

January 2016

Ongoing cardiovascular trials with incretin therapies

FAQsFAQs







Risk of pancreatitis with incretin therapy?

higher risk of pancreatitis for type 2 diabetes

vs. general population.2.1 fold 2.1 fold

Type 2 diabetes is associated with an elevated risk of pancreatitis

Incretin therapies have been associated with isolated cases of pancreatitis in trials and postmarketing reports

Causality relationship has not yet been established

Not recommended that these agents be used in patients with a history of pancreatitis

1. Garg R et al. Diabetes Care 2010;33:2359-54; 2. Liraglutide Canadian Product Monograph, Novo Nordisk Canada Inc., 2011. 3. Linagliptin Canadian Product Monograph, Boehringher Ingelheim (Canada) Ltd. July 26, 2011. 4. Exenatide Canadian Product Monograph, Eli Lilly Canada, 2011.

FAQsFAQs







Case studies: Carl

Carl 42 years old

Newly diagnosed with chronic kidney disease

Private insurance coverage

What would you consider for Carl?

Diabetes duration

5 years

Weight 92 kg

BMI 29.4 kg/m2

Waist circumference

109 cm

eGFR 64 ml/min

A1C 7.6%

FPG 7.2 mmol/L

PPG 10.9 mmol/L

Current treatment

Metformin (1000 mg BID)

1. Saxagliptin Canadian Product Monograph, Bristol Myers Squibb/Astra Zeneca, 2012; 2. Sitagliptin Canadian Product Monograph, Merck Frosst, 2012; 3. Liraglutide Canadian Product Monograph, Novo Nordisk Canada, 2010; 4. Exenatide Canadian Product Monograph, Eli Lilly Canada, 2011. 5. Linagliptin Canadian Product Monograph,

Boehringer Ingelheim (canada) Ltd., 2012; 6. CDA Guidelines. Can J Diabetes. 2013;37(suppl 1):S1-212.

29-15 59-30 89-60 ≥90 <15

Contraindicated

Caution/Reduced Dose

Safe

Exenatide

Saxagliptin

GFR (ml/min):

CKD=chronic kidney disease

GFR=glomerular filtration rate

CKD Stage:

Liraglutide

Linagliptin

Sitagliptin

RENALLY CLEARED?

Not Recommended

How does renal function influence the use of the different incretin therapies?

10 цg bid

1.2 & 1.8 mg

5 mg

100 mg

5 mg 50

50

50

15

50

Not Studied

25 mg 50 mg

2.5 mg

5 цg bid

Not Studied

30

30

Case studies: Carl

Carl 42 years old

Newly diagnosed with chronic kidney disease


What would you consider for Carl?

Diabetes duration

5 years

Weight 92 kg

BMI 29.4 kg/m2

Waist circumference

109 cm

eGFR 64 ml/min

A1C 7.6%

FPG 7.2 mmol/L

PPG 10.9 mmol/L

Current treatment


FAQsFAQs







Case studies: Joan

Joan 71 years old

Has had type 2 diabetes for 22 years

Public insurance coverage

What would you consider for Joan?

Weight 70 kg

BMI 27.3 kg/m2

Waist circumference

90 cm

Blood Pressure 138/84 mm Hg

A1C 8.9%

FPG 7.2 mmol/L

PPG 11.9 mmol/L

Current treatment

Metformin (1000 mg BID)Gliclazide (80mg)Basal insulin (25 units)Statin

FAQsFAQs







Case studies: Stephanie

Stephanie 51 years old

Newly diagnosed with type 2 diabetes


What would you consider for Stephanie?

Diabetes duration

6 months

Weight 68 kg

BMI 26.6 kg/m2

Waist circumference

101 cm

A1C 7.5%

FPG 8.7 mmol/L

PPG 9.1 mmol/L

Current treatment


FAQsFAQs







Case studies: George

George 63 years old

Has had diabetes for 7 years but recently has not been achieving his target A1C


What would you consider for George?

Diabetes duration

7 years

Weight 83 kg

BMI 27.7 kg/m2

Waist circumference

109 cm

A1C 7.8%

FPG 9.2 mmol/L

PPG 10.4 mmol/L

Current treatment

Metformin (1000 mg BID)Sitagliptin (100mg QD)Glyburide (10mg QD)

FAQsFAQs







Case studies: Tim

Tim 65 years old

Has recently been experiencing nocturnal hypoglycemia


What would you consider for Tim?

Diabetes duration

15 years

Weight 88 kg

BMI 27.2 kg/m2

Waist circumference

99 cm

A1C 6.7%

FPG 6.5 mmol/L

PPG 8.4 mmol/L

Current treatment

Metformin (1000 mg BID)NPH (56 units)

FAQsFAQs







Case studies: Andrea

Andrea 50 years old

Currently taking metformin and GLP-1 RA


What would you consider for Andrea?

Diabetes duration

4 years

Weight 70 kg

BMI 27.7 kg/m2

Waist circumference

101 cm

A1C 7.7%

FPG 8.1 mmol/L

PPG 9.7 mmol/L

Current treatment

Metformin (1000 mg BID)GLP-1 RA

A1C Weight Hypoglycemia

Adding-on insulin to GLP-1 receptor agonists

*Significant difference. Liraglutide is not indicated for use with insulin in Canada.1. DeVries et al. Diabetes Care 2012; 35(7):1446-54.

BL 7.6%

-0.5%* -0.05kg*

vs. -1.02kg

0.286* events/patient-

year

vs. 0.029 events/patient-year

vs. +0.02%

Metforrmin + Liraglutide 1.8 mg

Metformin + Liraglutide 1.8 mg + Detemir

A1C Weight Hypoglycemia

Adding-on GLP-1 receptor agonists to insulin

*Significant difference. Liraglutide is not indicated for use with insulin in Canada.1. Buse J et al. Ann Intern Med 2011; 154(2):103-12.

BL 8.4%

-1.74%* -1.8kg*

vs. +1.0kgvs. -1.04% vs. 1.2 events/patient-year

1.4 events/patient-

year

BID Placebo + Glargine + Met +/- OAD

BID Exenatide + Glargine + Met +/- OAD

R

Incretin or insulin therapy: Which comes first?

• Potential to delay need for insulin

• No need to downwardly adjust established insulin dose

• GLP-1 receptor agonist use may help to overcome phobias of insulin

• Lack of weight gain can help to offset weight gain associated with insulin

• If nausea is a concern, tolerance is established before insulin is introduced

Reasons to start incretin before insulin:

Adapted from Vora et al. Diabetes & Metabolism 2013;39:6–15.

FAQsFAQs







beyond metformin dr clayton feb 22

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