Literature DB >> 29476414

Insulin Matters: A Practical Approach to Basal Insulin Management in Type 2 Diabetes.

Lori Berard1, Noreen Antonishyn2, Kathryn Arcudi3, Sarah Blunden4, Alice Cheng5,6,7, Ronald Goldenberg8, Stewart Harris9, Shelley Jones10, Upender Mehan11,12, James Morrell13, Robert Roscoe14, Rick Siemens15, Michael Vallis16,17, Jean-François Yale18.   

Abstract

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.

Entities:  

Keywords:  Basal insulin; Glycemic target; Insulin initiation; Insulin titration; Patient barriers; Patient follow-up; Treatment delay; Type 2 diabetes

Year:  2018        PMID: 29476414      PMCID: PMC6104258          DOI: 10.1007/s13300-018-0375-7

Source DB:  PubMed          Journal:  Diabetes Ther            Impact factor:   2.945


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 [2-4]. 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 [5]. The usual starting point for insulin therapy in T2D is with basal insulin owing to its simplicity and lower risk of hypoglycemia [7].

When and in Whom to Initiate Insulin in T2D

The panel recommendations as to when and in whom to initiate insulin are summarized in Table 1.
Table 1

When and in whom to initiate insulin in T2D

When to consider insulin initiationWhen NOT to initiate insulin
Maximally tolerated non-insulin agents but A1C above the individualized target (usually 7.0%)New diagnosis A1C ≥ 8.5%Metabolic decompensationEnd-organ failurePatients with previous or current gestational diabetesAcute illnessProlonged course of steroidsIntolerance to oral medicationsAny time you consider this is an appropriate option for your patients from diagnosis onwardsThere 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 expectancyPeople limited in their capacity (physical or cognitive) to manage their diabetes who are at greater risk of hypoglycemia

[8]; http://guidelines.diabetes.ca/fullguidelines; http://www.rcn.org.uk; https://www.rcn.org.uk/professional-development/publications/pub-002254

When and in whom to initiate insulin in T2D [8]; http://guidelines.diabetes.ca/fullguidelines; http://www.rcn.org.uk; https://www.rcn.org.uk/professional-development/publications/pub-002254

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 [9-12]. 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 [11-15]. 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% [12]. There are many barriers that contribute to this delay in initiation and intensification of insulin in T2D. It is important to emphasize that many of these barriers reflect the attitudes and beliefs of both patient and provider. Identifying and addressing both provider and patient beliefs and attitudes are therefore essential to mitigate those barriers (Tables 2 and 3).
Table 2

Provider barriers

Provider barriersPanel recommendations to address provider barriers
Concerns about the risks to patients [3, 11, 16, 17]:Recognize the low risk of hypoglycemia and weight gain with earlier use of basal insulin in T2D [18, 19]
  Excess weight gain  Hypoglycemia  Impaired quality of lifeRecognize the lower risk of hypoglycemia with each successive generation of basal insulin (human vs analogue vs next generation analogue) [14, 2032]
Assumptions about patient inability to use insulinAssumptions about patient refusal to use insulinDiscuss with your patient. Do not assume that your patient is uninterested or non-adherent. Negotiate benefit versus risk or initiation versus inaction [3, 34]
Awareness that most people can manage their treatment with appropriate education and support [3, 17]
[3, 11, 17, 33]Diabetes education and allied support (cognitive behavior therapy and motivational communication) by healthcare professionals (HCPs) to improve adherence and health outcomes [16, 3336]
Lack of resources [3, 11, 16, 17, 33]:  Drug costs  Availability of staff  Skills needed to support insulin initiation  TimeInclude the family members/caregivers in the educational and ongoing support [34, 37, 38]Consider getting support from qualified team members or community [3, 34, 36]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 [9]Recognize that delaying therapy prevents patients from achieving A1C targets and increases the occurrence of major diabetes complications [9, 12]
Table 3

Patient barriers [39–43]

ConcernPanel recommendations
Fear of needles or apprehension toward injectionsFeeling that insulin is too complicated[3, 11, 16, 33, 44]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 veinInvite 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 insulinEducating on injections: see http://www.fit4diabetes.com/canada-english/fit-recommendations/
Feeling that this is a personal failure [3, 11, 16, 33, 45]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 [46]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
Belief that insulin causes diabetes complications [3, 11, 16, 33]Insulin is a natural hormone and a replacement therapy [42]Explain why insulin becomes necessary for most patients with diabetes eventually; it is not a punishment [46]Explain that use of insulin will help achieve glycemic target and minimize the risk of complications [47, 48]
Concerns over hypoglycemia (BG < 4.0 mmol/L) [3, 11, 16, 33, 4952]Reassure the patient that most hypoglycemic episodes are mild. Severe hypoglycemia (defined as requiring assistance by another person) is relatively rarea [52] http://guidelines.diabetes.ca/browse/chapter14;[53] http://guidelines.diabetes.ca/browse/chapter13; [20, 29, 42, 47, 54]Educate the patient on how to recognize and respond to symptoms [52] http://guidelines.diabetes.ca/browse/chapter14Make sure the patient and partner/family (if applicable) know how to recognize, treat, and avoid hypoglycemia, and how to self-adjust insulin [34]Choose insulins and regimens with lower rates of hypoglycemia [14, 29]Use systematic desensitization to allow the patient to work from a psychologically safe zone to a medically safe zone
Concerns over weight gain [3, 11, 16, 33]Encourage healthy diet and moderate exercise. Monitor weight. http://guidelines.diabetes.ca/fullguidelinesCombine insulin with metformin or other NIAHA with weight benefit. http://guidelines.diabetes.ca/cdacpg_resources/CPG_Quick_Reference_Guide_WEB.pdf [14, 29]Explain that weight gain with basal insulin regimens is small especially with newer basal insulin analogues (1–2 kg) [14, 20, 2629, 32]
Belief that insulin can never be stopped and will restrict lifestyle [3, 4, 16, 33, 42]Offer a 3-month trial period with subsequent reassessment. http://guidelines.diabetes.ca/fullguidelinesRecall that engaging the patient in the decision empowers them and leads to better outcomes [3, 4]Prescribe once-daily basal insulin that minimizes inconvenience and is easy to use. http://guidelines.diabetes.ca/bloodglucoselowering/insulinprescriptiontool

NIAHA non-insulin anti-hyperglycemic agent, BG blood glucose

aIn UKPDS, the annual incidence of severe hypoglycemia in insulin-treated patients was < 3%. With the newer long-acting basal insulins this is even lower (2.3%) [47]

Provider barriers Patient barriers [39-43] NIAHA non-insulin anti-hyperglycemic agent, BG blood glucose aIn UKPDS, the annual incidence of severe hypoglycemia in insulin-treated patients was < 3%. With the newer long-acting basal insulins this is even lower (2.3%) [47]

What is Your Role in Insulin Therapy?

Success in overcoming patient barriers relies greatly on listening to the patient and proactively addressing their fears and concerns [55, 56]. Open dialogue with the patient throughout the continuum of diabetes management, with an emphasis on the positive benefits of insulin therapy, will significantly enhance the outcomes for patients with diabetes. See Table 4 for review of action points with your patient.
Table 4

A new LEASE on insulin management [55]

Listen and askActively listen to fears and concerns. Normalize these concerns before discussing alternativesInvite discussion, show conviction of belief and supportive body language
EducateAsk permission to educate about the importance of insulin, the progressive nature of the disease, how to self-manage their disease
AddressProactively address patient concerns that may deter initiation and adherence to insulinAsk questions, identify the barriers, outline goals
SupportEnlist support of diabetes management teamProvide continuous support and education through the course of treatment
EmpowerEncourage 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 dietBe 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
A new LEASE on insulin management [55]

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) [58].

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, 59–64] and engage the patient, which in turn can lower barriers to insulin therapy [4, 65, 66]. Clear instructions to the patient on how the dose will be titrated, to manage expectations which will empower the patient and improve adherence to therapy [3, 4, 16, 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?

Three generations of basal insulins are available in Canada. The first generation of basal insulin is NPH, a human insulin that has been available for many decades, since 1946. The basal analogues (insulins detemir and glargine (Gla-100)) emerged in the 2000s and provided longer duration of action, improved day-to-day variability, reduced hypoglycemia, especially nocturnal, and did not require resuspension (as does NPH) [67]. A next generation of long-acting basal insulins—insulins glargine 300 U/mL (Gla-300) and degludec—have emerged with an extended action profile, improved safety, and the advantage of being administered in smaller volumes [29]. Table 5 summarizes the main characteristics of the currently available basal insulins. The panel recognizes that the choice of basal insulin may depend on access, cost, and clinical judgment with respect to the patient’s individual needs and lifestyle [29].
Table 5

Basal insulins

Insulin classificationDuration of actionCV safetyRisk of nocturnal hypoglycemiaConsiderations
Intermediate-actingNPH~ 18 h+++Needs resuspensionAdministered usually twice daily
Long-actingDetemir16–24 h++Administered once or twice daily
Gla-100~ 24 hDemonstrated (neutral)++Administered once daily, same time of dayAvailable in a fixed-ratio combination with lixisenatide
Next generationGla-300 (U300)~ 30 hbDemonstrateda (neutral)+Smaller volume (U300)Administered once dailyFlexible +
Degludec (U100, U200)~ 30 hbDemonstrated (neutral)+Option smaller volume (U200)Administered once dailyFlexible ++U100 available in a fixed-ratio combination with liraglutide

Duration of action and considerations: http://guidelines.diabetes.ca/fullguidelines/chapter12; [14, 29, 68–78]. Degludec and Gla-300 studies: [18, 20–28, 30–32, 70, 79, 80]

Gla-100 glargine 100 U/mL, Gla-300 glargine 300 U/mL

+ Insulins with low risk of hypoglycemia; ++ Insulins with moderate risk of hypoglycemia; +++ Insulins with higher risk of causing hypoglycemia

aBased on results from ORIGIN with Gla-100

bPK/PD studies at 0.4 U/kg

Basal insulins Duration of action and considerations: http://guidelines.diabetes.ca/fullguidelines/chapter12; [14, 29, 68–78]. Degludec and Gla-300 studies: [18, 20–28, 30–32, 70, 79, 80] Gla-100 glargine 100 U/mL, Gla-300 glargine 300 U/mL + Insulins with low risk of hypoglycemia; ++ Insulins with moderate risk of hypoglycemia; +++ Insulins with higher risk of causing hypoglycemia aBased on results from ORIGIN with Gla-100 bPK/PD studies at 0.4 U/kg

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 [8]. 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 [66]. 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 [8]. Box 1A details the recommendations by the panel for basal insulin dose and titration.

Box 1A: 2017 recommendations by the panel for basal insulin dose and titration

Panel recommendationsComments
The initial dosea10 U/day[19, 22, 59] http://guidelines.diabetes.ca/browse/appendices/appendix3 Other considerations:   0.2 U/kg/day [68, 82]   Using FBG as starting point: e.g., if FBG is 16 mmol/L start at 16 U [59]May need to be lower for some patients—recall that the starting dose should be individualized [14] http://guidelines.diabetes.ca/cdacpg_resources/CPG_Quick_Reference_Guide_WEB.pdf 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 longerDiscuss and negotiate your patient’s expectation
Fasting SMBG targetTarget 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[19, 20, 59, 80, 8385]Individualize target with a step approach (within 3 months) [14] http://guidelines.diabetes.ca/cdacpg_resources/CPG_Quick_Reference_Guide_WEB.pdf Important to educate that diabetes is a progressive disease and this is a moving target [4]
Dose adjustmentsSelect a simple titration algorithm that matches patient lifestyle [57]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 is1 unit every dayb [19, 63, 64, 66]Other titration algorithms include:2 units twice weekly based on lowest fasting SMGB value of the last 3 days [26, 27, 62, 86]Every week, based on lowest fasting SMGB value of the last 3 days [26, 63, 64]Other considerations:  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 [57]  For other considerations, see Table 6Measure glucose level at least every morning before breakfastc [57] http://guidelines.diabetes.ca/browse/appendices/appendix3 Remind patient to adjust the basal insulin based on morning glucose not bedtime glucosec [57]Assess for possible hypoglycemia (< 4.0 mmol/L) and decrease titration [52] http://guidelines.diabetes.ca/fullguidelines/chapter14Recognize that patient fear of hypoglycemia is easily elicited (hypoglycemia is a traumatic stress) and that providers underestimate the psychological impact of nonsevere hypoglycemia [51]Mitigating hypoglycemia:Is there an identifiable cause? [52] http://guidelines.diabetes.ca/fullguidelines/chapter14Teach patients how to prevent, recognize, and treat hypoglycemia [52] http://guidelines.diabetes.ca/fullguidelines/chapter14Confirm with patient that it is not “pseudo-hypoglycemia”. Explain what pseudo-hypoglycemiad is and ways to mitigate it [54]If no identifiable and preventable cause is identified, reduce the doseConfirm patient is using an accurate glucometer
Optimal/maximum basal insulin doseEducate the patient of their expected dose [3, 57]In most studies: 40 to 50 units is needed [8, 19, 26, 27, 66]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 [87]FBG in target, but A1C above target

BG blood glucose, FBG fasting blood glucose, SMBG self-monitored blood glucose

aFor more information on how to handle any oral agents and other FAQs, see Tables 6 and 7

bAlgorithm proven safe and effective with insulin glargine 100 units/mL (Lantus®) and 300 units/mL (Toujeo™)

cAdjust accordingly if shift worker

dPseudo-hypoglycemia: an event in which the patient experiences symptoms of hypoglycemia with a BG > 3.9 mmol/L but approaching that level [54]

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 BG blood glucose, FBG fasting blood glucose, SMBG self-monitored blood glucose aFor more information on how to handle any oral agents and other FAQs, see Tables 6 and 7
Table 6

Frequently asked questions and concerns

QuestionAnswer
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 [8]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 recommendedIf 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 insulinTest more frequentlyIf problems eating or hydrating: stop metformin, SGLT2 inhibitor, insulin secretagogue, ACE inhibitor, ARBs, diuretic, NSAIDsUse 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 [88]
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 unsureTest more frequentlyIf values rise, may consider giving half the dose [88]Additional comments: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 frequentlyTake extra snack at bedtimeWake up every 2–3 h to test glucose. If < 7.0 mmol/L, take an extra snack [88]Additional comments: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 advicePhone 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 doseIf > 12 h: consider omitting dose or give 50% when remember and 50% next dose and resume as per usual dosing administration schedule [89] Additional comments Recall that new long-acting basal insulins provide greater flexibility [24, 86]
Does insulin stacking (build-up of insulin in the circulation) occur with the long-acting basal insulins? [90]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 [90]
When to consider seeking support from other HCPs? [87]Patient has surpassed 1 U/kg/day of basal insulin without sufficient FBG controlPatient has recurrent episodes of hypoglycemiaPatient 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? [87]Patient has frequent episodes of unexplained hypoglycemiaPatient 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 occurredAt 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

SGLT2 sodium-glucose co-transporter 2, ACE angiotensin-converting enzyme, ARB angiotensin receptor blockers, NSAIDs non-steroidal anti-inflammatory drugs

Table 7

What to do with previous drugs [8, 57, 91, 92]: usually continue all current anti-hyperglycemic agents when initiating basal insulin

Anti-hyperglycemic agentAnti-hyperglycemic agents when initiating basal insulinComments
MetforminContinued
Insulin secretagogues(meglitinide and sulfonylurea (SU))Options to continue, reduce, or stop the sulfonylurea [7, 8, 93]Option to continue, reduce, or stop meglitinide [8]If SU is stopped or reduced, titration of insulin is even more importantWhen 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 [94]
TZDsUsually discontinueda [95]Due to increased risk of edema and heart failure with insulin [8, 96]
Incretin agents (GLP-1R agonist, DPP4i)Continueda [8, 97]
SGLT2 inhibitorContinued

GLP-1R glucagon-like peptide-1 receptor, DPP4i protease dipeptidyl peptidase-4 inhibitor, SGLT2 sodium-glucose co-transporter 2, TZD thiazolidinedione

aRecommendation to decrease TZDs is not indicated in Canada; linagliptin use with insulin is off-label (Trajenta®)

bAlgorithm proven safe and effective with insulin glargine 100 units/mL (Lantus®) and 300 units/mL (Toujeo™) cAdjust accordingly if shift worker dPseudo-hypoglycemia: an event in which the patient experiences symptoms of hypoglycemia with a BG > 3.9 mmol/L but approaching that level [54]

Frequent Questions and What to Do with Previous Drugs When Initiating Basal Insulin

Tables 6 and 7 outline some of the frequently encountered questions and concerns facing HCPs when initiating and titrating basal insulin. Frequently asked questions and concerns SGLT2 sodium-glucose co-transporter 2, ACE angiotensin-converting enzyme, ARB angiotensin receptor blockers, NSAIDs non-steroidal anti-inflammatory drugs What to do with previous drugs [8, 57, 91, 92]: usually continue all current anti-hyperglycemic agents when initiating basal insulin GLP-1R glucagon-like peptide-1 receptor, DPP4i protease dipeptidyl peptidase-4 inhibitor, SGLT2 sodium-glucose co-transporter 2, TZD thiazolidinedione aRecommendation to decrease TZDs is not indicated in Canada; linagliptin use with insulin is off-label (Trajenta®)

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) [87]. The panel provides guidelines for medical follow-up with patients in Box 2.

Box 2: panel recommendations for medical follow-up with diabetes HCPs [87, 91]

WhenWhat and why
24–72 hWhen initiating insulin or titrationSupport insulin initiation and reinforce titration
1–2 week(s)Patients report BG readingsEnsure titration is occurring normally
1 monthPatients report BG readingsEnsure titration is occurring normally (it is encouraged to continue with biweekly contacts thereafter)
3 monthsA1C measurementIf not at goal, patient may continue with titration for another 3 monthsThis contact point should occur in person or by virtual consult
6 monthsA1C measurementFollow-up of titrationIf A1C above target, review glycemic profile and consider adding mealtime insulin
Within 24 h of hypoglycemiaEducate patient on recognizing, preventing, and treating hypoglycemiaIf recurrent hypoglycemia occurs, re-evaluate titration schedule or reduce dose (frequent, recurrent hypoglycemia is typically defined as 1–2 lows in 1 week)

Panel Recommendations for Medical Follow-up with Diabetes HCPs

Box 2: panel recommendations for medical follow-up with diabetes HCPs [87, 91]

Conclusion

Several factors underlie the importance of the initiative put forth by this expert panel: there is a rising prevalence of diabetes [98]; half of the T2D population is not at target, among which 61% were receiving insulin therapy [99], 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.
  81 in total

1.  Ultra-long-acting insulin degludec has a flat and stable glucose-lowering effect in type 2 diabetes.

Authors:  T Heise; L Nosek; S G Bøttcher; H Hastrup; H Haahr
Journal:  Diabetes Obes Metab       Date:  2012-07-10       Impact factor: 6.577

2.  New insulin glargine 300 Units · mL-1 provides a more even activity profile and prolonged glycemic control at steady state compared with insulin glargine 100 Units · mL-1.

Authors:  Reinhard H A Becker; Raphael Dahmen; Karin Bergmann; Anne Lehmann; Thomas Jax; Tim Heise
Journal:  Diabetes Care       Date:  2014-08-22       Impact factor: 19.112

3.  New Long-Acting Basal Insulins: Does Benefit Outweigh Cost?

Authors:  Eberhard Standl; David R Owen
Journal:  Diabetes Care       Date:  2016-08       Impact factor: 19.112

Review 4.  Understanding how pharmacokinetic and pharmacodynamic differences of basal analog insulins influence clinical practice.

Authors:  Jennifer Goldman; Christoph Kapitza; Jeremy Pettus; Tim Heise
Journal:  Curr Med Res Opin       Date:  2017-06-23       Impact factor: 2.580

Review 5.  Barriers and facilitators to starting insulin in patients with type 2 diabetes: a systematic review.

Authors:  C J Ng; P S M Lai; Y K Lee; S A Azmi; C H Teo
Journal:  Int J Clin Pract       Date:  2015-07-06       Impact factor: 2.503

Review 6.  Breaking down patient and physician barriers to optimize glycemic control in type 2 diabetes.

Authors:  Stuart A Ross
Journal:  Am J Med       Date:  2013-09       Impact factor: 4.965

7.  Three-year efficacy of complex insulin regimens in type 2 diabetes.

Authors:  Rury R Holman; Andrew J Farmer; Melanie J Davies; Jonathan C Levy; Julie L Darbyshire; Joanne F Keenan; Sanjoy K Paul
Journal:  N Engl J Med       Date:  2009-10-22       Impact factor: 91.245

Review 8.  Clinical evidence for the earlier initiation of insulin therapy in type 2 diabetes.

Authors:  David R Owens
Journal:  Diabetes Technol Ther       Date:  2013-06-20       Impact factor: 6.118

9.  Risk of hypoglycaemia in type 2 diabetes patients under different insulin regimens: a primary care database analysis.

Authors:  Karel Kostev; Franz W Dippel; Wolfgang Rathmann
Journal:  Ger Med Sci       Date:  2015-01-12

10.  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).

Authors:  G B Bolli; M C Riddle; R M Bergenstal; M Ziemen; K Sestakauskas; H Goyeau; P D Home
Journal:  Diabetes Obes Metab       Date:  2015-02-12       Impact factor: 6.577

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  4 in total

1.  Expert Opinion: A Call for Basal Insulin Titration in Patients with Type 2 Diabetes in Daily Practice: Southeast European Perspective.

Authors:  Nicolae Hancu; Andrej Janez; Nebojsa Lalic; Nikolaos Papanas; Dario Rahelic; Gabriela Roman; Cristian Serafinceanu; Nikolaos Tentolouris; Blaženko Vukovic; Agron Ylli; Tsvetalina Tankova
Journal:  Diabetes Ther       Date:  2021-03-15       Impact factor: 2.945

Review 2.  Weight Change and the Association with Adherence and Persistence to Diabetes Therapy: A Narrative Review.

Authors:  Kristina S Boye; Shraddha Shinde; Tessa Kennedy-Martin; Susan Robinson; Vivian T Thieu
Journal:  Patient Prefer Adherence       Date:  2022-01-06       Impact factor: 2.711

Review 3.  A practical approach to the clinical challenges in initiation of basal insulin therapy in people with type 2 diabetes.

Authors:  Thomas Forst; Pratik Choudhary; Doron Schneider; Bruno Linetzky; Paolo Pozzilli
Journal:  Diabetes Metab Res Rev       Date:  2020-12-01       Impact factor: 4.876

4.  Practical guidance on the initiation, titration, and switching of basal insulins: a narrative review for primary care.

Authors:  Roopa Mehta; Ronald Goldenberg; Daniel Katselnik; Louis Kuritzky
Journal:  Ann Med       Date:  2021-12       Impact factor: 4.709

  4 in total

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