Advancements in Basal Insulin: Tailoring Treatment to Patient Needs Friday, November 10, 2017 | 12:30-13:30 Session ID no. 186648-090 After attending this session, participants will be able to: Recognize the role of basal insulin therapy in the T2DM treatment continuum. Identify and overcome barriers to insulin initiation and optimization from the patient and physician perspective, including hypoglycemia. Differentiate basal insulin options, with a focus on the newer basal insulins. Individualize basal insulin treatment based on patient characteristics and insulin profiles. An ancillary session at the 2017 Family Medicine Forum This program has been certified by the College of Family Physicians of Canada and the Quebec office for up to 1.00 Group Learning credits. This program was supported in part by educational funding from Novo Nordisk Canada Inc. Jean-François Yale, MD, CSPQ, FRCPC Professor of Medicine, Division of Endocrinology & Metabolism, McGill University Health Centre Dr. Yale is a Professor of Medicine in the Division of Endocrinology and Metabolismat the McGill University Health Centre. Dr. Yale chaired the clinical and scientific section of the Canadian Diabetes Association (CDA; now Diabetes Canada) from 1992 to 1994, chaired the expert panel that published the guidelines for hypoglycemia in 2001, and is a member of the committee. Dr. Yale has been the Director for the development of CDA clinical practice guidelines for the prevention and treatment of diabetes since 1995. His research interests (195 publications) include the prevention of hypoglycemia, intensive treatment of type 1 and 2 diabetes, and involvement in many multicentre studies including ACCORD, ORIGIN, TECOS, and SAVOR-TIMI.
Transcript
Advancements in Basal Insulin: Tailoring Treatment to Patient Needs Friday, November 10, 2017 | 12:30-13:30 Session ID no. 186648-090 After attending this session, participants will be able to:
Recognize the role of basal insulin therapy in the T2DM treatment continuum. Identify and overcome barriers to insulin initiation and optimization from the patient
and physician perspective, including hypoglycemia. Differentiate basal insulin options, with a focus on the newer basal insulins. Individualize basal insulin treatment based on patient characteristics and insulin
profiles.
An ancillary session at the 2017 Family Medicine Forum
This program has been certified by the College of Family Physicians of Canada and the Quebec office for up to 1.00 Group Learning credits.
This program was supported in part by educational funding from Novo Nordisk Canada Inc.
Jean-François Yale, MD, CSPQ, FRCPC Professor of Medicine, Division of Endocrinology & Metabolism, McGill University Health Centre
Dr. Yale is a Professor of Medicine in the Division of Endocrinology and Metabolismat the McGill University Health Centre. Dr. Yale chaired the clinical and scientific section of the Canadian Diabetes Association (CDA; now Diabetes Canada) from 1992 to 1994, chaired the expert panel that published the guidelines for hypoglycemia in 2001, and is a member of the committee. Dr. Yale has been the Director for the development of CDA clinical practice guidelines for the prevention and treatment of diabetes since 1995. His research interests (195 publications) include the prevention of hypoglycemia, intensive treatment of type 1 and 2 diabetes, and involvement in many multicentre studies including ACCORD, ORIGIN, TECOS, and SAVOR-TIMI.
Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Sanofi, Takeda • Consulting Fees: Abbott, AstraZeneca, Bayer, Boehringer-Ingelheim, Eli Lilly,
Janssen, Merck, Novo Nordisk, Sanofi, Takeda • Other – participated in clinical trial: Bayer, Boehringer-Ingelheim, Eli Lilly,
Mylan, Sanofi
Disclosure of commercial support
• This program has received financial support from Novo Nordisk Canada Inc. in the form of educational funding
• This program has received in-kind support from Novo Nordisk Canada Inc. in the form of logistical support
• Potential for conflict(s) of interest:• Dr. Yale has received payment/funding, etc. from the companies listed in the disclosures
whose products are discussed in the program, including: • Eli Lilly Canada Inc.: Insulin glargine U100 (Basaglar™), Insulin NPH (Humulin®)• Sanofi-aventis Canada Inc.: Insulin glargine U100 (Lantus®), Insulin glargine U300 (Toujeo™)
• Novo Nordisk Canada Inc. distributes three products that will be discussed in this program:• Insulin NPH (Novolin® ge)• Insulin detemir (Levemir®)• Insulin degludec (Tresiba®)
• Dr. Yale will receive an honorarium from the CFPC/FMF committee for this session
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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, the College of Family Physicians of Canada, the FMOQ (Fédération des médecins omnipraticiens du Québec), the Canadian Council on Continuing Education in Pharmacy (CCCEP) and the Ordre du PharmaciensQuébec (OPQ)
• All data have been sourced from clinically accepted evidence
• All support used in justification of patient care recommendations conforms to generally accepted standards, the Canadian Diabetes Association 2013 Clinical Practice Guidelines and 2016 interim update, as well as the most recently available clinical data
Planning committee
• Vladimir Milosevic, MD, FRCPC• Staff Endocrinologist, Trillium Health Partners, Mississauga, Ontario
• Pierre Filteau, MD, CCFP• Family Physician, Centre Medical des Carrières (GMF, groupe de médecine familiale), Saint-
Canadian Diabetes Association. Types of Insulin. Available at: http://guidelines.diabetes.ca/cdacpg_resources/Ch12_Table1_Types_of_Insulin_updated_Aug_5.pdf. Accessed on April 30, 2017.; Novo Nordisk Canada Inc. Tresiba® Product Monograph. 2017.
The need for basal insulin in T2DM: Type 2 diabetes is progressive and is characterized by
a decline in β-cell function and insulin resistance
Treatment will need to be adjusted and intensified over time, and insulin may be required
Impairedglucosetolerance
100
75
50
25
0Years from Diagnosis
Bet
a Cel
l Fun
ctio
n (%
)
-12 -10 -6 -2 0 2 6 10 14
Postprandial hyperglycemia
Type 2 diabetes phase I
Type 2 diabetes phase II
Type 2 diabetes phase III
• 50% of ß-cell function is already lost at diagnosis
• ß-cell function will continue to decline despite treatment
Lebovitz H. Insulin secretagogues: old and new. Diabetes Reviews. 1999;7(3):139-153; UK Prospective Diabetes Study Group. UK Prospective Diabetes Study 16: overview of 6 years' therapy of type II diabetes: a progressive disease. Diabetes. 1995;44(11):1249-1258; Leibowitz G, et al. β‐Cell failure in type 2 diabetes. J Diabetes Investig. 2011;2(2):82-91.
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Short- and long-term benefits of basal insulin therapy in T2DM
Most potent antihyperglycemic effect with no dose ceiling
Early glucose control reduces the risk of macro- and microvascular complications
A1C
1%reduction
in A1C
14%reduction
14%reduction
37%reduction
Fatal/non-fatal MI All-cause mortality
Microvascular endpoints
Relative risk reduction sustained long term
Lovre D, et al. Benefits of timely basal insulin control in patients with type 2 diabetes. Journal of Diabetes and its Complications. 2015;29(2):295-301; Stratton IM, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes(UKPDS 35): prospective observational study. BMJ. 2000;321(7258):405-412; Holman RR, et al. 10-Year Follow-up of Intensive Glucose Control in Type 2 Diabetes. New Engl J Med. 2008;359(15):1577-1589.
Factors to consider when individualizing insulin treatment in T2DM
CDA = Canadian Diabetes Association (now Diabetes Canada)
The 2016 CDA Clinical Practice Guidelines Interim Update continues to recommend insulin as an option for second-line treatment in T2DM
CDA Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2013 clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes. 2013;37:S1-212.
H
FPG
A1CEffective A1C controlReminder: no dose ceiling
Effective FPG lowering Minimizing weight gain
Minimizing risk of hypoglycemia
Cardiovascular safety
Increased use of basal insulin
relative to previous surveys
Basal insulin use has increased, but targets are still not being met
DM-SCAN survey in T2DM (2012)
Only 50% of patients achieving A1C ≤7%
on insulin only
on insulin + ≥1 NIAHA
+
DM-SCAN=Diabetes Mellitus Status in Canada; NIAHA=non-insulin antihyperglycemic agent; T2DM=type 2 diabetes mellitus
Leiter LA, et al. Type 2 diabetes mellitus management in Canada: Is it improving? Can J Diabetes. 2013;37(2):82-89.
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Why is glycemic control not being achieved with insulin?
PERCEPTIONS
OF INSULINHYPOGLYCEMIA AND FEAR OF
LOWS
PERCEIVEDDOSE
CEILING
Despite insulin being a potential 2nd-line add-on to metformin…
Peyrot M, et al. Correlates of Insulin Injection Omission. Diabetes Care. 2010;33(2):240-245; Kostev K, et al. Changes in time to insulin initiation in type 2 diabetes patients: a retrospective database analysis in Germany and UK (2005–2010). Primary Care Diabetes. 2013;7(3):229-233; Leiter LA, et al. Assessment of the impact of fear of hypoglycemic episodes on glycemic and hypoglycemia management. Can J Diabetes. 2005;29(3):186-192; Peyrot M, et al. Insulin adherence behaviours and barriers in the multinational Global Attitudes of Patients and Physicians in Insulin Therapy study. Diabetic Med. 2012;29(5):682-689; Brod M, et al. Understanding the economic, daily functioning, and diabetes management burden of non-severe nocturnal hypoglycemic events in Canada: differences between type 1 and type 2. J Med Econ. 2014;17(1):11-20; Brod M, et al. Impact of self-treated hypoglycaemia in type 2 diabetes: a multinational survey in patients and physicians. Curr Med Res Opin. 2012;28(12):1947-1958.
FEAR OFNEEDLES
Perceptions of insulin
Insulin diabetes complications
Insulin = patient “failure”
Insulin = death or “end-of-line”
Insulin ≠ positive impact on treatment and health
TRUE or FALSE?
Leiter LA, et al. Assessment of the impact of fear of hypoglycemic episodes on glycemic and hypoglycemia management. Can J Diabetes. 2005;29(3):186-192; Peyrot M, et al. Insulin adherence behaviours and barriers in the multinational Global Attitudes of Patients and Physicians in Insulin Therapy study. Diabetic Med. 2012;29(5):682-689; Hunt LM, et al. NIDDM patients' fears and hopes about insulin therapy: the basis of patient reluctance. Diabetes Care. 1997;20(3):292-298.
Hypoglycemia is the most common adverse event in insulin therapy, regardless of A1C level
51.4%
Khunti K, et al. Rates and predictors of hypoglycaemia in 27,585 people from 24 countries with insulin‐treated type 1 and type 2 diabetes: the global HAT study. Diabetes Obes Metab. 2016; Reichert SM, et al. A Population-based Study on Incidence and Associated Risk Factors for Hypoglycemia in Canada: The InHYPO-DM Study. Presented at: 52nd European Association for the Study of Diabetes (EASD) Annual Meetings; Sept 13-15, 2016; Munich, Germany; Leiter LA, et al. Assessment of the impact of fear of hypoglycemic episodes on glycemic and hypoglycemia management. Can J Diabetes. 2005;29(3):186-192; Aronson R et al. Can J Diabetes. 2017 May 17. pii: S1499-2671(16)30781-X. doi: 10.1016/j.jcjd.2017.01.007. [Epub ahead of print].
Overallhypoglycemia
events per patient-year
Nocturnalhypoglycemia
Severehypoglycemia
HAT study & IN-HYPO survey in T2DM
experiencedin last 30 days (non-severe daytime hypoglycemia)
29.7%
experienced in last 30 days
events per patient-year
events per patient-year
37.9% experiencedin last year
37.3 12.7 1.8
85% of Canadian patients do not speak to their physicians about hypoglycemia
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The burden of hypoglycemia
Physiological Psychological Financial
Increased fear leading to:
Mood changes
Changes in behaviour
Reduced or skipped doses
Increased PG monitoring
Work absenteeism/ presenteeism
Increased visits to clinic
Continued poor glycemic control
Increased risk of long-term health consequences, e.g., mortality
Weight gain
Desouza CV, et al. Hypoglycemia, diabetes, and cardiovascular events. Diabetes Care. 2010;33(6):1389-1394; Bonds DE, et al. The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. BMJ. 2010;340:b4909; Brod M, et al. Understanding the economic, daily functioning, and diabetes management burden of non-severe nocturnal hypoglycemic events in Canada: differences between type 1 and type 2. J Med Econ. 2014;17(1):11-20; Frier BM. Hypoglycaemia in diabetes mellitus: epidemiology and clinical implications. Nat Rev Endocrinol. 2014;10(12):711-722; Yeaw J, et al. Cost of self-monitoring of blood glucose in Canada among patients on an insulin regimen for diabetes. Diabetes Ther. 2012;3(1):7.
Module 2: Basal Insulin
Options
Properties of an ideal basal analogue
• Control fasting blood glucose with one injection per day in all individualsLonger duration of action
• Lower risk of hypoglycemiaFlat time-action profile (no peak)
• Potential for titration to lower FPG target without hypoglycemia
Predictability (less day-to-day and within-day
variability)
What does “variability” mean?i
Kohnert, Klaus-Dieter, Lutz Vogt, and Eckhard Salzsieder. “Advances in understanding glucose variability and the role of continuous glucose monitoring.” European Endocrinol 6.1 (2010): 53-56.
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What are our basal insulin options in 2017?
Novolin® geNPH
Humulin® N
Levemir®
U100
Lantus®
Basaglar™
U300
Toujeo™
Tresiba®
U100/U200
NPH Insulin detemir (IDet)
Insulin glargine (IGlar)
Insulin degludec (IDeg)
Basal insulin through timeAnimal insulin
preparations NPH insulinIsolation of insulin(Banting & Best)
Adapted from Cahn A, et al. New forms of insulin and insulin therapies for the treatment of type 2 diabetes. Lancet Diabetes Endocrinol. 2015;3(8):638-652; Novo Nordisk Canada Inc. Novolin® ge Product Monograph. 2016; Eli Lilly Canada Inc. Humulin® N Product Monograph. 2016; Novo Nordisk Canada Inc. Levemir® Product Monograph. 2016.; Sanofi-aventis Canada Inc. Lantus® Product Monograph. 2016.; Eli Lilly Canada Inc. BASAGLARTM Product Monograph. 2015; Sanofi-aventis Canada Inc. ToujeoTM Product Monograph. 2015; Novo Nordisk Canada Inc. Tresiba® Product Monograph. 2017; Mannucci E, et al. Cardiovascular effects of basal insulins. Drug Healthc Patient Saf. 2015;7:113; Peterson GE. Intermediate and long-acting insulins: a review of NPH insulin, insulin glargine and insulin detemir. Curr Med Res Opin. 2006;22(12):2613-2619.
(CV safety shownfor ORIGIN)
NPH > IGlar > IDet
Mode of protraction: How do the options compare?
Crystals
NPH and insulin glargine form precipitates at injection site that delays dissolution and absorption
Insulin glargine image data on file.; Seested T, et al. Ultrastructural Visualization of Insulin Degludec Multi-hexamers in the Subcutaneous Depot In Vivo Supports a Unique Mechanism of Protraction. Can J Diabetes. 2012;36(5):S61; Novo Nordisk Canada Inc. Novolin® ge Product Monograph. 2016; Sanofi-aventis Canada Inc. Lantus® Product Monograph. 2016; Sanofi-aventis Canada Inc. ToujeoTM Product Monograph. 2015; Sanofi-Aventis Deutschland GmbH. Toujeo Summary of Product Characteristics (SmPC). Frankfurt am Main, Germany. 2015.
larger end-of-trial dose(15% greater dose with U300)
mean weight change(non-significant: 0.49 kg gained vs. 0.71 kg)
FPG mean decrease(-3.41 mmol/L vs. -3.80 mmol/L)
Bolli G, et al. New insulin glargine 300 U/ml compared with glargine 100 U/ml in insulin‐naïve people with type 2 diabetes on oral glucose‐lowering drugs: a randomized controlled trial (EDITION 3). Diabetes, Obesity and Metabolism. 2015;17(4):386-394.
A1C
(%
)
H1⁰ hypoglycemia endpoint% reporting hypo (wk 9 6 months)(non-significant for confirmed or severe hypoglycemia [overall & nocturnal])
Zinman B, et al. Insulin degludec versus insulin glargine in insulin-naive patients with type 2 diabetes. Diabetes Care. 2012;35(12):2464-2471.
A1C
(%)
FPG
A1C
H
non-inferiority achieved
similar end-of-trial dose(0.59 U/kg vs. 0.60 U/kg)
mean weight change(non-significant: 2.4 kg gained vs. 2.1 kg)
larger mean change(significant: -3.8 mmol/L vs. -3.30 mmol/L)
1° hypoglycemia endpointAnnual hypo rateSignificant reduction for nocturnal and severe; non-significant for overall
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Is the hypoglycemia risk reduction “real”?
Challenges
Open-label design
Excluded patients at risk of hypoglycemia
More rigorous design
Double-blind & crossover
Enrolled patients with a high risk of hypoglycemia
For example:• experienced a severe hypo within the
last year
• eGFR 30–59 mL/min/1.73m2
• had hypoglycemia unawareness
Wysham C, et al. Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 2 Diabetes: The SWITCH 2 Randomized Clinical Trial. JAMA. 2017;318(1):45-56.
IDeg vs. IGlar U100: Comparable A1C lowering & lower hypoglycemia rate, for patients at high risk of hypoglycemia
FPG
A1C
H
non-inferiority achieved
similar end-of-trial dose(smaller dose increase with IDeg assessed by post-hoc analysis)
FPG mean change(mean FPG decreased to 6.0 mmol/L vs. 6.1 mmol/L )
1⁰ hypoglycemia endpointAnnual hypo rateSignificant reduction for overall, nocturnal and severe
mean weight change(non-significant: at crossover and at end of trial)
Wysham C, et al. Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 2 Diabetes: The SWITCH 2 Randomized Clinical Trial. JAMA. 2017;318(1):45-56.
Cardiovascular safety of basal insulin established in two long-term, cardiovascular outcome trials
Open-label design
Glargine vs. standard of care
>12,000 patients at high risk of CV events: • With IFG, IGT or newly detected
T2DM, or established T2DM• Insulin-naïve• Mean A1C: 6.5%• Mean diabetes duration: 5.4 yrs
DEVOTE – DegludecStudy Design
Double-blind design
Degludec vs. glargine U100 each in combination with standard of care
>7,000 patients at high risk of CV events: • With T2DM• Insulin-naïve or experienced• Mean A1C: 8.4%• Mean diabetes duration: 16 yrs
ORIGIN – Glargine U100Study Design
Origin Trial Investigators. Rationale, design, and baseline characteristics for a large international trial of cardiovascular disease prevention in people with dysglycemia: the ORIGIN Trial (Outcome Reduction with an Initial Glargine Intervention). Am J Heart. 2008;155(1):26. e21-26. e13; Marso SP, et al. Design of DEVOTE (Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Patients With Type 2 Diabetes at High Risk of Cardiovascular Events)–DEVOTE 1. Am Heart J. 2016;179:175-183.
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Cardiovascular safety of basal insulin established in two long-term, cardiovascular outcome trials
Non-inferiority• HR: 1.00 vs. SOC
Hypoglycemia • Severe and non-severe:
significantly increased
DEVOTE – DegludecResults
Non-inferiority• HR: 0.91 vs. IGlar U100
Hypoglycemia • Severe: significantly decreased
ORIGIN – Glargine U100Results
ORIGIN Trial Investigators. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012;2012(367):319-328; Marso SP et al. Efficacy and safety of degludec versus glargine in type 2 diabetes. N Engl J Med. DOI: 10.1056/NEJMoa1615692.
H
Basal insulin product options and features
Brand name Total units per pen (units)
Maximum dose for injection (units)
In use time (days) Pen type
NPH
Novolin® ge NPH100 U/mL 300 60 28 Cartridge
Humulin® N100 U/mL 300 60 28 KwikPen®*
Insulin detemir Levemir®
100 U/mL 300 80 42 FlexTouch®*
Insulin glargine
Lantus®
100 U/mL 300 80 28 SoloSTAR®*
Basaglar™100 U/mL 300 60 28 KwikPen®
Toujeo™300 U/mL 450 80 42 SoloSTAR®
Insulin degludec
Tresiba®
100 U/mL 300 80 56 FlexTouch®
Tresiba®
200 U/mL 600 160 56 FlexTouch®
Novo Nordisk Canada Inc. Novolin® ge Product Monograph. 2016.; Eli Lilly Canada Inc. Humulin® N Product Monograph. 2016; Novo Nordisk Canada Inc. Levemir® Product Monograph. 2016.; Sanofi-aventis Canada Inc. Lantus® Product Monograph. 2016; Eli Lilly Canada Inc. BASAGLARTM Product Monograph. 2015; Sanofi-aventis Canada Inc. ToujeoTM Product Monograph. 2015; Novo Nordisk Canada Inc. Tresiba® Product Monograph. 2017.
*Also available in cartridges for use in durable/refillable pens; max dose in durable pen may differ from max dose in prefilled pens above
Module 3: Case studies
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Tips to streamline basal insulin starts and follow-ups
1) Block time to discuss and start insulin and to follow-up with Allied HCPs
2) Start Basal Insulin Checklist
3) Basal Insulin Follow-up Checklist
Peyrot M, et al. Insulin adherence behaviours and barriers in the multinational Global Attitudes of Patients and Physicians in Insulin Therapy study. Diabetic Med. 2012;29(5):682-689.
Vishal, 57Construction worker
Private Coverage
HEALTH STATUS• Diagnosed with T2DM diabetes 8 years ago• Has never been prescribed insulin• A1C: 8.8%• BMI: 33.0 kg/m2
• Medications: Metformin, DPP-4 inhibitor, SGLT2 inhibitor and rosuvastatin
OTHER INFORMATION• Missed a follow-up appointment due to temporary relocation
for job• “I saw my father have a severe hypoglycemic event when he
took insulin. I’m afraid that will happen to me.”
Case #1: Vishal
Is Vishal a good candidate to initiate basal insulin?
A. YesB. No, he should stay on his current regimenC. No, he should add another/switch to another NIAHAD. Other
NIAHA = non-insulin antihyperglycemic agent
Discuss with those around you or write in your notebook
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1. Explain why insulin is needed
3. Demonstrate the pen
4. Educate the patient on low blood sugar
5. Book a follow-up appointment For additional insights, refer to
guidelines.diabetes.ca/insulin
2. Explain how to start and adjust
Canadian Diabetes Association. Insulin pen start checklist. Available at: http://guidelines.diabetes.ca/cdacpg_resources/insulin_start_checklist.pdf. Retrieved April 30, 2017.
Start Basal Insulin Checklist – Vishal
1. Explain why insulin is neededOver time, the pancreas produces less insulin, causing elevated blood sugar and possibly complications
“I saw my father have a severe low when he took insulin. I’m afraid that
will happen to me.”
How would you address Vishal’s concerns?
Adapted from: Lebovitz H. Insulin secretagogues: old and new. Diabetes Reviews. 1999;7(3):139-153; CDA Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2013 clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes. 2013;37:S1-212; Fonseca VA. Defining and characterizing the progression of type 2 diabetes. Diabetes Care. 2009;32(suppl 2):S151-S156.
Discuss with those around you or write in your notebook
fearmisconceptionsresistance
Start Basal Insulin Checklist – Vishal
2. Explain how to start and adjust
Teach how to titrate basal insulin
Ultra-long-acting2
(Tresiba®)
• START with 10 units once daily• ADJUST dose once a week based on
1 FPG value from that morning• increase by 4 units if above
individualized target• DOSE once daily
1. Canadian Diabetes Association. Insulin pen start checklist. Available at: http://guidelines.diabetes.ca/cdacpg_resources/insulin_start_checklist.pdf. Retrieved April 30, 2017; 2. Philis-Tsimikas A, et al. Insulin degludec once-daily in type 2 diabetes: simple or step-wise titration (BEGIN: ONCE SIMPLE USE). Adv Ther. 2013;30(6):607-622.
REMEMBER: Insulin has no dose ceiling!
Long-acting1
(Lantus®, Levemir®, Toujeo™)
• START with 10 units once daily• ADJUST dose once a day based on
1 FPG value from that morning• increase by 1 unit if above
individualized target• DOSE once daily at the same time
each day
Start Basal Insulin Checklist – Vishal
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Example basal insulin prescriptions
RxTresiba® FlexTouch®
200 U/mL+needles
Start at 10 units once daily
Titrate once a week until FPG target (5.5 mmol/L*) reached If above FPG target, + 4 unitsIf below FPG target, - 4 units
RxLantus® SoloSTAR®
100 U/mL+needles
Start at 10 units once daily
Titrate once a day until FPG target (5.5 mmol/L*) reachedIf above FPG target, + 1 unitsIf below FPG target, - 1 units
*Target can be modified based on patient characteristics, i.e., elderly patients.
3. Demonstrate the pen
Show a sample injection*or*
give the 1st injection in office
Arrange step-by-step, hands-on training with allied health team
FIT Forum for Injection Technique Canada. Recommendations for Best Practice in Injection Technique 3rd Edition. 2016. Available at: http://www.fit4diabetes.com/files/2314/8777/6632/FIT_Recommendations_3rd_Edition_2017.pdf. Retrieved April 30, 2017.
McAulay V, et al. Symptoms of hypoglycaemia in people with diabetes. Diabetic Med. 2001;18(9):690-705; Canadian Diabetes Association. Lows and highs: blood glucose levels. 2013. Available at: http://guidelines.diabetes.ca/cdacpg/media/documents/patient-resources/lows-and-highs-blood-glucose-level-feb2014.pdf. Retrieved April 30, 2017.
Encourage your patients to track their lows and to discuss them with you.
Nocturnal
• Nightmares, night sweats• Irritability upon waking• Morning headache• Impaired thinking/
sluggishness the next day
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Start Basal Insulin Checklist – Vishal
4. Educate the patient on low blood sugar
Driving recommendations for patients treated with insulin(non-commercial drivers)
1. Measure SMBG immediately before and at least every 4 hours
2. Have SMBG equipment and fast-acting carbohydrate within easy reach
3. Stop driving, test and treat as soon as hypoglycemia and/or impaired driving are suspected
4. Do not drive when BG level is <4.0 mmol/LIf BG is <4.0 mmol/L, persons should not drive until at least 45 minutes after ingestion of carbohydrate and BG is at least 5.0 mmol/L
What are you going to follow-up on with Vishal?
5. Book a follow-up appointment
Start Basal Insulin Checklist – Vishal
Case #1: Vishal’s 1 month follow-up
HEALTH STATUS• Has been taking basal insulin for 1 month• Current dose: 28 units
• Says he is hesitant to continue increasing dose• FPG: 8.9 mmol/L (↓ 4.3 mmol/L)
OTHER INFORMATION• “I have been feeling ‘off’.”• “My dose is almost 3 times what it was when I started.”• “One time I fell asleep before taking my dose. I called the
pharmacy in the morning when I remembered, but I wasn’t really sure how much to take.”
Vishal, 57Construction worker
Private Coverage
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Basal Insulin Follow-up Checklist
1. How is the patient is progressing toward target FPG?
3. Assess injection technique and site rotation
4. Determine next steps
2. Ask about hypoglycemia at every visit
Basal Insulin Follow-up Checklist – Vishal
1. How is the patient progressing toward target?
Review progress toward FPG target
“My dose is almost 3 times what it was when I started.”“One time I fell asleep before taking my dose.”
Address patient concerns
8.9 mmol/L (↓ 4.3 mmol/L last month)
28 units (started at 10 U)
Insulin has no maximum dose!If a dose is missed:
• NPH/IGlar/IDeto Check BG frequently; do not double dose
• IDego Based on clinical trials, changing the
dosing time does not compromise efficacy or safety. Inject when remembered; ensure minimum 8 hours between doses
What is the current basal insulin dose?
Kadowaki T, et al. Efficacy and safety of once‐daily insulin degludec dosed flexibly at convenient times vs fixed dosing at the same time each day in a Japanese cohort with type 2 diabetes: A randomized, 26‐week, treat‐to‐target trial. J Diabetes Investig. 2016;7(5):711-717; Novo Nordisk Canada Inc. Tresiba® Product Monograph. 2017; Novo Nordisk Canada Inc. Novolin® ge Product Monograph. 2016; Eli Lilly Canada Inc. Humulin® N Product Monograph. 2016; Novo Nordisk Canada Inc. Levemir® Product Monograph. 2016.; Sanofi-aventis Canada Inc. Lantus® Product Monograph. 2016.
Basal Insulin Follow-up Checklist – Vishal
2. Ask about hypoglycemia at every visit
Symptoms BG <4 mmol/L
• How many times was BG <4 mmol/L?
• How often did they experience symptoms?
Factors
• Time of day, type of meal, activity & exercise?
Review
• Review prevention & management
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Basal Insulin Follow-up Checklist – Vishal
3. Assess injection technique and site rotation
How many times did the patient use each needle?
Ask the patient to show you where they inject
FIT Forum for Injection Technique Canada. Recommendations for Best Practice in Injection Technique 3rd Edition. 2017. Available at: http://www.fit4diabetes.com/files/2314/8777/6632/FIT_Recommendations_3rd_Edition_2017.pdf. Retrieved July 13, 2017.
Basal Insulin Follow-up Checklist – Vishal
What are your next steps with Vishal?
4. Determine next steps
A) No changeB) Continue titrating basal dose to targetC) Discontinue basal insulin and add a NIAHAD) Switch to a different basal insulinE) A combination of the above
Discuss with those around you or write in your notebook
Case #2: Deborah
HEALTH STATUS• Diagnosed with T2DM diabetes 12 years ago• On 43 units of NPH insulin for 4 years • A1C: 7.9%• BMI: 30.4 kg/m2
• FPG: 8.8 mmol/L• Shared that some days it’s 5 mmol/L and other days it’s
• Medications: NPH, metformin, DPP-4 inhibitor, gliclazide, fluvastatin and valsartan
OTHER INFORMATION• “I haven’t been sleeping well. I wake up sweaty and have
frequent headaches in the morning.”• “I haven’t told my daughter; she will worry because I had
a severe hypoglycemic event last winter.”• “I do not want to increase my insulin dose further.”
Deborah, 69Retired Post Office
EmployeePrivate Coverage
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Review progress toward FPG target
“I wake up sweaty and have frequent headaches in the morning.”“I had a severe event last winter.”
Address patient concerns
8.8 mmol/L (range 4–15 mmol/L)(A1C 7.9%)
43 units of NPH insulin for 4 years(also on gliclazide)
Deborah’s dose is causing variable control and hypoglycemia. Her FPG is not getting to target.
What is the current basal insulin dose?
Basal Insulin Follow-up Checklist – Deborah
1. How is patient progressing toward target?
Basal Insulin Follow-up Checklist – Deborah
2. Ask about hypoglycemia at every visit
Symptoms BG <4 mmol/L
• Both hypoglycemia and hyperglycemia
• “I haven’t been sleeping well. I wake up sweaty and have frequent headaches in the morning.”
Factors
• Nocturnal hypoglycemia
• Fear of severe low• Type of meal,
activity & exercise?
Review
• Review options to reach target and reduce hypoglycemia
Basal Insulin Follow-up Checklist – Deborah
3. Assess injection technique and site rotation
How many times did the patient use each needle?
Ask the patient to show you where they inject
FIT Forum for Injection Technique Canada. Recommendations for Best Practice in Injection Technique 3rd Edition. 2017. Available at: http://www.fit4diabetes.com/files/2314/8777/6632/FIT_Recommendations_3rd_Edition_2017.pdf. Retrieved July 13, 2017.
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Basal Insulin Follow-up Checklist – Deborah
4. Determine next steps
Discuss with those around you or write in your notebook
A) No changeB) Advise Deborah to increase snackingC) Reduce NPH doseD) Split NPH into 21 units qam + 22 units qpmE) Switch to a basal insulin analogueF) Stop gliclazide
What are your next steps with Deborah?
Basal Insulin Follow-up Checklist – Deborah
4. Determine next steps
Discuss with those around you or write in your notebook
A) No changeB) Advise Deborah to increase snackingC) Reduce NPH doseD) Split NPH into 21 units qam + 22 units qpmE) Switch to a basal insulin analogueF) Stop gliclazide
What are your next steps with Deborah?
Action to reduce low BG Reach target? OtherConsiderations
Switch to insulin analogue Yes ↓ hypoglycemia,cost/coverage
Stop gliclazide No↑ NPH dose;
hypoglycemia may continue
Review: How to switch basal insulins in T2DM
20% 20%
From IGlar U3001,2
From BID basal1,2,3,4
1:1From once-daily basal1,2,3,4
1. Sanofi-aventis Canada Inc. Lantus® Product Monograph. 2016; 2. Eli Lilly Canada Inc. BASAGLARTM Product Monograph. 2015; 3. Sanofi-aventis Canada Inc. ToujeoTM Product Monograph. 2015; 4. Novo Nordisk A/S. Tresiba® Summary of Product Characteristics (SmPC). Bagsværd, Denmark. 2015.
Followed by daily or weeklytitration (depending on insulin)
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Summary
All insulins have high efficacy
• Start low, go slow• Keep increasing the
dose until FPG target is reached safely
• No maximum dose
A1C HGet to target with as
few hypoglycemic episodes as possible
• Basal insulin analogues are recommended over NPH due to lower nocturnal hypoglycemia
• IDeg demonstrated lower overall, severe and nocturnal hypoglycemia vs. IGlar U100
Proven cardiovascular safety
• ORIGIN (IGlar U100) demonstrated CV safety vs. standard of care
• DEVOTE (IDeg) demonstrated CV safety vs. IGlar U100
Minimize weight gain
• Insulin analogues may have less weight gain than NPH
Novo Nordisk Canada Inc. Novolin® ge Product Monograph. 2016.; Eli Lilly Canada Inc. Humulin® N Product Monograph. 2016; Novo Nordisk Canada Inc. Levemir® Product Monograph. 2016; Sanofi-aventis Canada Inc. Lantus® Product Monograph. 2016; Eli Lilly Canada Inc. BASAGLARTM Product Monograph. 2015; Sanofi-aventis Canada Inc. ToujeoTM Product Monograph. 2015; Novo Nordisk Canada Inc. Tresiba® Product Monograph. 2017; Mannucci E, et al. Cardiovascular effects of basal insulins. Drug Healthc Patient Saf. 2015;7:113; Marso SP et al. Efficacy and safety of degludec versus glargine in type 2 diabetes. N Engl J Med. DOI: 10.1056/NEJMoa1615692; CDA Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2013 clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes. 2013;37:S1-212.
Advancements in Basal Insulin: Tailoring Treatment to Patient Needs
Ancillary Session at the Family Medicine Forum | CERT+ Session ID# 186648-090 Evaluation Form
Date: Location: Friday, November 10, 2017 at 12:30 p.m. Palais des congrès, Montreal Please rate the question in this evaluation according to the following scale:
The Program The program content enhanced my knowledge. 1 2 3 4 5 The program was relevant to my practice. 1 2 3 4 5 The program met the stated learning objectives. 1 2 3 4 5 The program addressed a gap in my knowledge. 1 2 3 4 5 The program was well organized. 1 2 3 4 5 Adequate time was allotted for interaction and discussion. 1 2 3 4 5 The Presenter The presenter delivered the content clearly. 1 2 3 4 5 Questions and discussions were well moderated. 1 2 3 4 5 Time was efficiently managed. 1 2 3 4 5 Please indicate which CanMEDS-FM roles you felt were addressed during this educational activity. (select all that apply) Family Medicine Expert Collaborator Scholar Manager Communicator Health Advocate Professional
Did the activity respect the « Ethical code of CME Providers1 »? � Yes � No If not, please explain (Ref.: 1. http://www.cemcq.qc.ca)
Did you perceive any degree of bias in any part of the program? Yes No If yes, please explain:
Please describe what you felt was the most effective part of the program.
Please identify an important concept/idea that you learned.
How will you change your practice based on what you learned today? 1. 2.
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