Insulin Matters: A Practical Approach to Basal Insulin Management in Type 2 Diabetes
It is currently estimated that 11 million Canadians are living with diabetes or prediabetes. Although hyperglycemia is associated with serious complications, it is well established that improved glycemic control reduces the risk of microvascular complications and can also reduce cardiovascular (CV) complications over the long term. The UKPDS and ADVANCE landmark trials have resulted in diabetes guidelines recommending an A1C target of ≤ 7.0% for most patients or a target of ≤ 6.5% to further reduce the risk of nephropathy and retinopathy in those with type 2 diabetes (T2D), if it can be achieved safely. However, half of the people with T2D in Canada are not achieving these glycemic targets, despite advances in diabetes pharmacological management. There are many contributing factors to account for this poor outcome; however, one of the major factors is the delay in treatment advancement, particularly a resistance to insulin initiation and intensification. To simplify the process of initiating and titrating insulin in T2D patients, a group of Canadian experts reviewed the evidence and best clinical practices with the goal of providing guidance and practical recommendations to the diabetes healthcare community at large. This expert panel included general practitioners (GPs), nurses, nurse practitioners, endocrinologists, dieticians, pharmacists, and a psychologist. This article summarizes the panel recommendations.
KeywordsBasal insulin Glycemic target Insulin initiation Insulin titration Patient barriers Patient follow-up Treatment delay Type 2 diabetes
Basal Insulin Initiation
Do We Still Need Insulin?
Type 2 diabetes (T2D) is a progressive disorder characterized by multiple pathophysiological defects. The core defects include insulin resistance in the muscle and liver and impaired insulin secretion due to β-cell failure [1, 2]. The progressive nature of the disease is such that it requires therapy to be intensified over time to compensate for the ongoing β-cell deficiency [2, 3, 4]. At the time of T2D diagnosis, more than 50% of β-cells have already been lost, and continue to decline at an average rate of 5% per year [1, 2, 5]. Therefore, the use of insulin is an appropriate option at any point in the management of T2D to replace the insulin that the pancreas is unable to produce sufficiently [1, 6]. In fact, when the maximum output of insulin has decreased to 15% or 20% of normal, non-insulin anti-hyperglycemic agents can no longer sustain glycemic control and insulin supplementation becomes a necessity . The usual starting point for insulin therapy in T2D is with basal insulin owing to its simplicity and lower risk of hypoglycemia .
When and in Whom to Initiate Insulin in T2D
When and in whom to initiate insulin in T2D
When to consider insulin initiation
When NOT to initiate insulin
Maximally tolerated non-insulin agents but A1C above the individualized target (usually 7.0%)
New diagnosis A1C ≥ 8.5%
Patients with previous or current gestational diabetes
Prolonged course of steroids
Intolerance to oral medications
Any time you consider this is an appropriate option for your patients from diagnosis onwards
There are no contraindications for the use of insulin but insulin may not be appropriate for:
Some older, asymptomatic patients, who may not gain sufficient benefit because of short life expectancy
People limited in their capacity (physical or cognitive) to manage their diabetes who are at greater risk of hypoglycemia
What are the Barriers to Insulin Initiation?
Clinical inertia, defined as the failure on the part of the provider to advance therapy when required, adversely affects timely management of T2D [9, 10, 11, 12]. Insulin is often initiated late in the course of the disease, after failure with multiple antihyperglycemic agents, and at glycemic values well above the recommended targets [11, 12, 13, 14, 15]. In Canada, mean A1C levels are > 8.5% and mean diabetes duration is ≥ 9 years before initiation of basal insulin in T2D patients [13, 15]. A UK retrospective study of pharmacologically treated T2D patients on one, two, or three oral antihyperglycemic agents reported that the median time to insulin initiation was > 7 years with an A1C ≥ 7.0% and the mean A1C levels at initiation was > 9.0% .
Panel recommendations to address provider barriers
Excess weight gain
Impaired quality of life
Assumptions about patient inability to use insulin
Assumptions about patient refusal to use insulin
Availability of staff
Skills needed to support insulin initiation
Utilize resources from Diabetes Canada including:
The Insulin Prescription Tool: http://guidelines.diabetes.ca/bloodglucoselowering/insulinprescriptiontool and videos: http://guidelines.diabetes.ca/insulin
Reluctance to utilize insulin early in the diagnosis of T2D 
Fear of needles or apprehension toward injections
Feeling that insulin is too complicated
Demonstrate injection technique: show the insulin pen and small needle tips. Apply the principles of systematic desensitization (self-controlled exposure)
Highlight that the injection is into subcutaneous tissue, not a vein
Invite patient to try these without insulin, in your office (i.e., dry injection); give first injection together with patient to observe, support and ensure correct administration of insulin
Educating on injections: see
Pro-action. Do not wait to talk about insulin once the patient needs insulin. Explain from the time of diagnosis that insulin is a likely treatment option in the course of T2D 
Discuss with the patient, using decisional balance analysis (pros and cons), that need to advance therapy is due to the progressive nature of diabetes, not because the patient has done something wrong
Insulin is a natural hormone and a replacement therapy 
Explain why insulin becomes necessary for most patients with diabetes eventually; it is not a punishment 
Reassure the patient that most hypoglycemic episodes are mild. Severe hypoglycemia (defined as requiring assistance by another person) is relatively rarea  http://guidelines.diabetes.ca/browse/chapter14;
Make sure the patient and partner/family (if applicable) know how to recognize, treat, and avoid hypoglycemia, and how to self-adjust insulin 
Use systematic desensitization to allow the patient to work from a psychologically safe zone to a medically safe zone
Encourage healthy diet and moderate exercise. Monitor weight. http://guidelines.diabetes.ca/fullguidelines
Combine insulin with metformin or other NIAHA with weight benefit. http://guidelines.diabetes.ca/cdacpg_resources/CPG_Quick_Reference_Guide_WEB.pdf [14, 29]
Offer a 3-month trial period with subsequent reassessment. http://guidelines.diabetes.ca/fullguidelines
Prescribe once-daily basal insulin that minimizes inconvenience and is easy to use. http://guidelines.diabetes.ca/bloodglucoselowering/insulinprescriptiontool
What is Your Role in Insulin Therapy?
A new LEASE on insulin management 
Listen and ask
Actively listen to fears and concerns. Normalize these concerns before discussing alternatives
Invite discussion, show conviction of belief and supportive body language
Ask permission to educate about the importance of insulin, the progressive nature of the disease, how to self-manage their disease
Proactively address patient concerns that may deter initiation and adherence to insulin
Ask questions, identify the barriers, outline goals
Enlist support of diabetes management team
Provide continuous support and education through the course of treatment
Encourage and educate the patient on self-management: demonstrate how the pen works and let them try it, explain how to take medications, how to self-monitor blood glucose, how to prevent and treat hypoglycemia, reinforce healthy lifestyle and diet
Be comfortable with the principle of shaping: in other words, with repetition and support for next step goals, self-efficacy in a new behavior can develop
Basal Insulin Dose and Titration Recommendations
In light of the persistent barriers contributing to delays in diabetes management with insulin, there is an urgent need for a simplified and practical approach to the initiation and intensification of insulin. Complex regimens and unrealistic targets can worsen the patient’s engagement in the process and ultimately the patient’s well-being [3, 4, 57]. Simplification allows for empowerment by engaging the patient in doable tasks, which provides the context for behavior shaping (next step goals) and self-efficacy (confidence in the face of barriers) .
What Do We Want in a Basal Insulin Recommendation?
A starting dose that can be safely applied and individualized.
A titration schedule that is simple and can be safely patient-driven, with a fasting blood glucose (FBG) target that can be individualized. Patient-driven titration schedules are as effective as provider-driven titration schedules [19, 59, 60, 61, 62, 63, 64] and engage the patient, which in turn can lower barriers to insulin therapy [4, 65, 66].
Recognition that insulin initiation and titration are two separate behaviors for the patient, each of which needs to be addressed in relation to patient readiness to change.
How to Select a Basal Insulin?
Duration of action
Risk of nocturnal hypoglycemia
~ 18 h
Administered usually twice daily
Administered once or twice daily
~ 24 h
Administered once daily, same time of day
Available in a fixed-ratio combination with lixisenatide
~ 30 hb
Smaller volume (U300)
Administered once daily
Degludec (U100, U200)
~ 30 hb
Option smaller volume (U200)
Administered once daily
U100 available in a fixed-ratio combination with liraglutide
How to Dose?
There are several important concepts to remember when dosing basal insulin: (a) the starting dose will be wrong; (b) there is no maximal insulin dose; (c) titration of insulin dose is the key . Each of these concepts needs to be explicitly discussed and understood by the patient in order for titration to be successful. Despite 92% of physicians agreeing that “insulin intensification is an essential element of diabetes management,” 30% of primary care physicians “never or rarely” personally intensified insulin (vs 4% of specialists) in the multinational survey MODIFY [14, 81]. Interestingly, in a recent multinational survey, HCPs generally preferred a gradual and safe approach to titration to avoid hypoglycemia whereas patients are frustrated by time to reach goal . It is therefore important to manage the patient’s expectations.
The starting dose for basal insulin recommended by this panel is 10 U/day. The dose should be incrementally increased on a regular basis using target FBG as the determinant for dose adjustments. At initiation, educating patients that many people will need at least 40–50 units of basal insulin to achieve target FBG is useful for goal setting and behavior shaping. This may help mitigate patient fear/reluctance to up-titrate .
Box 1A details the recommendations by the panel for basal insulin dose and titration.
Box 1B provides a summary of key recommendations, including a starting dose and titration schedule.
Basal Insulin Dose and Titration Recommendations (2017)
Box 1A: 2017 recommendations by the panel for basal insulin dose and titration
The initial dosea
Using FBG as starting point: e.g., if FBG is 16 mmol/L start at 16 U 
May need to be lower for some patients—recall that the starting dose should be individualized 
The lower dosages have the advantage of decreasing the risk of a hypoglycemic reaction with the first injection, but make the titration period a bit longer
Discuss and negotiate your patient’s expectation
Fasting SMBG target
Target should be 4.0–7.0 mmol/L for most people
Patient/HCP contact recommended at 7.0 mmol/L. HCP may then suggest continuing to 4.0–5.5 mmol/L
Individualize target with a step approach (within 3 months) 
Important to educate that diabetes is a progressive disease and this is a moving target 
Select a simple titration algorithm that matches patient lifestyle 
The following dose adjustment algorithms have been shown to be safe and effective. Select the one that is easiest for the patient to follow:
One easy titration algorithm is
Other titration algorithms include:
If (nocturnal) hypoglycemia occurs (BG < 4.0 mmol/L) reduce the dose by 2–4 units, or 10% of the basal dose based on clinical judgement 
For other considerations, see Table 6
Measure glucose level at least every morning before breakfastc 
Remind patient to adjust the basal insulin based on morning glucose not bedtime glucosec 
Assess for possible hypoglycemia (< 4.0 mmol/L) and decrease titration  http://guidelines.diabetes.ca/fullguidelines/chapter14
Recognize that patient fear of hypoglycemia is easily elicited (hypoglycemia is a traumatic stress) and that providers underestimate the psychological impact of nonsevere hypoglycemia 
Is there an identifiable cause?  http://guidelines.diabetes.ca/fullguidelines/chapter14
Teach patients how to prevent, recognize, and treat hypoglycemia  http://guidelines.diabetes.ca/fullguidelines/chapter14
Confirm with patient that it is not “pseudo-hypoglycemia”. Explain what pseudo-hypoglycemiad is and ways to mitigate it 
If no identifiable and preventable cause is identified, reduce the dose
Confirm patient is using an accurate glucometer
Optimal/maximum basal insulin dose
Communicate how long it will take them to reach target (e.g., if the expected dose is 60 units at 1 U/day increase, then it will take on average 6 weeks)
Indication that basal insulin is not enough includes:
Up-titrations without a corresponding drop on BG (verify patient adherence and check injection sites). http://www.fit4diabetes.com/canada-english/fit-recommendations/
Patient has surpassed 1 U/kg/day of basal insulin without sufficient FBG control 
FBG in target, but A1C above target
Frequent Questions and What to Do with Previous Drugs When Initiating Basal Insulin
Frequently asked questions and concerns
Is 4.0 to 7.0 mmol/L too aggressive?
Depends on individual target and patient characteristics (e.g., younger patient, patient with established retinopathy/nephropathy, etc.). http://guidelines.diabetes.ca/cdacpg_resources/CPG_Quick_Reference_Guide_WEB.pdf
Is there a ceiling to titration process?
There is no such thing as a maximum dose 
Consider resuming titration when FBG values are above patient-agreed target for 3 consecutive days; resume 1 unit daily titration unti FBG < 7.0 mmol/L is reached without hypoglycemia
Patient/HCP contact recommended at 7.0 mmol/L
What to do if daytime hypoglycemia occurs while on secretagogues?
Dose adjustment of secretatogue and/or basal insulin recommended
If on NPH, consider basal analogue
When is it appropriate to intensify treatment with another agent?
When A1C level remains above individual target after 3–6 months despite appropriate treatment initiation and optimization have occurred or insulin dose is > 1.0 U/kg/day. http://guidelines.diabetes.ca/cdacpg_resources/CPG_Quick_Reference_Guide_WEB.pdf
What to do if sickness occurs?
Normally continue with the usual dose of basal insulin
Test more frequently
If problems eating or hydrating: stop metformin, SGLT2 inhibitor, insulin secretagogue, ACE inhibitor, ARBs, diuretic, NSAIDs
Use SADMANS http://guidelines.diabetes.ca/browse/appendices/appendix7_2015. Complete the card (accessed by clicking on the link) and give it to your patient, including when to call and whom to reach for support 
What to do if patient has recently been hospitalized for a few days?
Verify if the dosages were modified during the hospitalization. The dosages are often decreased as the patient eats hospital food, and must often be increased back towards the previous dosages
What to do if unsure whether the dose was given?
Do not give the dose if unsure
Test more frequently
If values rise, may consider giving half the dose 
Suggest using supportive tools or an insulin pen that has a memory feature that will indicate if the dose was given and when
What to do if gave the dose twice?
Test more frequently
Take extra snack at bedtime
Wake up every 2–3 h to test glucose. If < 7.0 mmol/L, take an extra snack 
Check available resources in area:
For example, call a nurse for advice, diabetes educator available for support, a 24 h pharmacy for a pharmacist’s advice
Phone an “on-call” service and consider referral to ER
What to do if missed a dose?
If < 6 h: take usual dose (be aware of potential increase in risk of hypoglycemia with next injection)
If 6–12 h: take 50% of normal dose
If > 12 h: consider omitting dose or give 50% when remember and 50% next dose and resume as per usual dosing administration schedule 
Does insulin stacking (build-up of insulin in the circulation) occur with the long-acting basal insulins? 
No, there will be a steady state reached. The steady state will take longer to reach the longer the half-life of the insulin, minimizing the fluctuations in insulin levels 
When to consider seeking support from other HCPs? 
Patient has surpassed 1 U/kg/day of basal insulin without sufficient FBG control
Patient has recurrent episodes of hypoglycemia
Patient lacks engagement in the titration process. It is important to explore reasons for lack of engagement by screening for diabetes distress
When to refer to a specialist? 
Patient has frequent episodes of unexplained hypoglycemia
Patient experiences complications (allergic reactions, lack of treatment response, edema, etc.)
A1C level remains above individual target after 3–6 months despite appropriate treatment initiation and optimization have occurred
At any point when comfort level is exceeded with available resources. It should be openly acknowledged that if either the patient or provider thinks they are “in over their head,” accessing additional resources is appropriate
Anti-hyperglycemic agents when initiating basal insulin
(meglitinide and sulfonylurea (SU))
Option to continue, reduce, or stop meglitinide 
If SU is stopped or reduced, titration of insulin is even more important
When stopping SUs:
Patients may need more insulin or go beyond basal insulin as glucose levels may go higher
As a guideline, stopping SU is equivalent to about 20 U of insulin. Individual results necessitate monitoring and titration 
Usually discontinueda 
Incretin agents (GLP-1R agonist, DPP4i)
Patient Support and Medical Follow-up
How to Ensure Success of Basal Insulin Management?
The success of basal insulin initiation and titration relies not only on identifying and addressing the patient and practitioner barriers but also on contact frequency with the patient. Post-initiation follow-up may occur by many means including via phone, text, email (depending on jurisdiction), cloud, or virtual consult. Regular contact presents an opportunity to provide or revisit diabetes education, to provide support to patients on how to effectively self-manage their disease and to identify any causes of concern [3, 34]. Furthermore, titration should be revisited when the patient is not achieving goal, hypoglycemia occurs, or there is a change in the insulin type or brand (e.g., biosimilar) .
The panel provides guidelines for medical follow-up with patients in Box 2.
Panel Recommendations for Medical Follow-up with Diabetes HCPs
What and why
When initiating insulin or titration
Support insulin initiation and reinforce titration
Patients report BG readings
Ensure titration is occurring normally
Patients report BG readings
Ensure titration is occurring normally (it is encouraged to continue with biweekly contacts thereafter)
If not at goal, patient may continue with titration for another 3 months
This contact point should occur in person or by virtual consult
Follow-up of titration
If A1C above target, review glycemic profile and consider adding mealtime insulin
Within 24 h of hypoglycemia
Educate patient on recognizing, preventing, and treating hypoglycemia
If recurrent hypoglycemia occurs, re-evaluate titration schedule or reduce dose (frequent, recurrent hypoglycemia is typically defined as 1–2 lows in 1 week)
Several factors underlie the importance of the initiative put forth by this expert panel: there is a rising prevalence of diabetes ; half of the T2D population is not at target, among which 61% were receiving insulin therapy , suggesting delayed insulin initiation and intensification; there are multiple titration algorithms to choose from which adds to the confusion and complexity for patients and providers; and the arrival of new long-acting basal insulins and other pharmacological and technological advances that require consideration. This document was developed by a multidisciplinary panel to address frequently asked questions on insulin initiation and titration, and it establishes simple and practical guidelines for diabetes HCPs for effective initiation and titration of basal insulin, with the intent that it may translate to effective glycemic outcomes in clinical practice.
Compliance with Ethical Guidelines
This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.
This publication was supported by Sanofi-Aventis Canada (Laval, Quebec), who funded editorial and managerial support in the preparation of this publication, provided by a third party, HIT Global Consulting Services Inc. The article processing charges were also funded by Sanofi-aventis Canada (Laval, Quebec).
Medical Writing and Editorial Assistance
The manuscript was designed, drafted, and edited by the panel with the help of medical writer, Maria Ferraiuolo of HIT Global Consulting Services Inc. The authors, individually and collectively, were responsible for content and editorial decisions.
The manuscript was conceived by the panel of experts recognized here as the co-authors. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. All authors had full access to all of the data used for this article and take complete responsibility for the integrity and accuracy of the data analysis.
Lori Berard has received consultancy/advisory board honorarium from Sanofi, Novo Nordisk, Eli Lilly, BD, and MontMed. Noreen Antonishyn has received consultancy/advisory board honorarium from Sanofi. Kathryn Arcudi has received consultancy/advisory board honorarium from Janssen, Abbott Nutrition, Astra Zeneca, Eli Lilly, and Sanofi. Sarah Blunden has received consultancy/advisory board honorarium from Ascencia, Abbott Diabetes, Eli Lilly, Medtronic, Roche Diagnostics, and Sanofi. Alice Cheng has received consultancy/advisory board honorarium, speaker honorarium, or research support from Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Sanofi, Servier, and Takeda. Ronald Goldenberg has received consultancy/advisory board honorarium, speaker honorarium, or research support from Eli Lilly, Novo Nordisk, and Sanofi. Stewart Harris has received consultancy/advisory board honorarium or research support from Sanofi, Novo Nordisk, AstraZeneca, Bi/Lilly, Merck, and Janssen. Shelley Jones has received consultancy/advisory board honorarium from Abbott, AZ, Janssen, Eli Lilly, Merck, Novo Nordisk, and Sanofi. Upender Mehan has received consultancy/advisory board honorarium or unrestricted funding from Sanofi, AstraZeneca, Amgen, Janssen, Novo Nordisk, and Dairy Farmers of Canada. James Morrell has received consultancy/advisory board honorarium or research support from AstraZeneca, Novo Nordisk, Island Health, Janssen, Eli Lilly, Abbott, and MontMed. Robert Roscoe has received consultancy/advisory board honorarium or speaker honorarium/other from Novo Nordisk, Abbott Diabetes Care, Janssen, AstraZeneca, Merck Canada, Sanofi Canada, Banting & Best Diabetes Program, New Brunswick Government, Becton–Dickinson Canada, Novo Nordisk Canada, Bayer Healthcare, BMS AstraZeneca, Pfizer Canada, Eli Lilly Canada, Medtronic Canada, Abbott Diabetes Care, Roche Diagnostics, Canadian Pharmacists Association, Canadian Diabetes Association, and New Brunswick Pharmacists Association. Rick Siemens has received consultancy/advisory board honorarium from Sanofi, AstraZeneca, Novo Nordisk, Lilly, Janssen, and Merck. Michael Vallis has received consultancy/advisory board honorarium, speaker honorarium, or research support from Sanofi, Novo Nordisk, Abbvie, Valeant, Merck, CSL Behring, and Pfizer. Jean-François Yale has received consultancy/advisory board honorarium or research support from Sanofi, Novo Nordisk, Eli Lilly, and Mylan.
Compliance with Ethics Guidelines
This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.
This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
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