| Literature DB >> 29476414 |
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
When and in whom to initiate insulin in T2D
| When to consider insulin initiation | When |
|---|---|
| Maximally tolerated non-insulin agents but A1C above the individualized target (usually 7.0%) | There are no contraindications for the use of insulin but insulin may not be appropriate for: |
[8]; http://guidelines.diabetes.ca/fullguidelines; http://www.rcn.org.uk; https://www.rcn.org.uk/professional-development/publications/pub-002254
Provider barriers
| Provider barriers | Panel recommendations to address provider barriers |
|---|---|
| Concerns about the risks to patients [ | Recognize the low risk of hypoglycemia and weight gain with earlier use of basal insulin in T2D [ |
| Excess weight gain | Recognize the lower risk of hypoglycemia with each successive generation of basal insulin (human vs analogue vs next generation analogue) [ |
| Assumptions about patient inability to use insulin | Discuss with your patient. Do not assume that your patient is uninterested or non-adherent. Negotiate benefit versus risk or initiation versus inaction [ |
| Awareness that most people can manage their treatment with appropriate education and support [ | |
| [ | Diabetes education and allied support (cognitive behavior therapy and motivational communication) by healthcare professionals (HCPs) to improve adherence and health outcomes [ |
| Lack of resources [ | Include the family members/caregivers in the educational and ongoing support [ |
| Reluctance to utilize insulin early in the diagnosis of T2D [ | Recognize that delaying therapy prevents patients from achieving A1C targets and increases the occurrence of major diabetes complications [ |
Patient barriers [39–43]
| Concern | Panel recommendations |
|---|---|
| Fear of needles or apprehension toward injections | Demonstrate injection technique: show the insulin pen and small needle tips. Apply the principles of systematic desensitization (self-controlled exposure) |
| Feeling that this is a personal failure [ | 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 [ |
| Belief that insulin causes diabetes complications [ | Insulin is a natural hormone and a replacement therapy [ |
| Concerns over hypoglycemia (BG < 4.0 mmol/L) [ | Reassure the patient that most hypoglycemic episodes are mild. |
| Concerns over weight gain [ | Encourage healthy diet and moderate exercise. Monitor weight. |
| Belief that insulin can never be stopped and will restrict lifestyle [ | Offer a 3-month trial period with subsequent reassessment. |
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]
A new LEASE on insulin management [55]
| Actively listen to fears and concerns. Normalize these concerns before discussing alternatives | |
| 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 | |
| Enlist support of diabetes management team | |
| 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 |
Basal insulins
| Insulin classification | Duration of action | CV safety | Risk of nocturnal hypoglycemia | Considerations | |
|---|---|---|---|---|---|
| Intermediate-acting | NPH | ~ 18 h | – | +++ | Needs resuspension |
| Long-acting | Detemir | 16–24 h | – | ++ | Administered once or twice daily |
| Gla-100 | ~ 24 h | Demonstrated (neutral) | ++ | Administered once daily, same time of day | |
| Next generation | Gla-300 (U300) | ~ 30 hb | Demonstrateda (neutral) | + | Smaller volume (U300) |
| Degludec (U100, U200) | ~ 30 hb | Demonstrated (neutral) | + | Option smaller volume (U200) | |
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
Box 1A: 2017 recommendations by the panel for basal insulin dose and titration
| Panel recommendations | Comments | |
|---|---|---|
| The | 10 U/day | May need to be lower for some patients—recall that the starting dose should be individualized [ |
| Fasting SMBG target | Target should be 4.0–7.0 mmol/L for most people | Individualize target with a step approach (within 3 months) [ |
| Dose adjustments | Select a simple titration algorithm that matches patient lifestyle [ | Measure glucose level at least every morning before breakfastc [ |
| Optimal/maximum basal insulin dose | Educate the patient of their expected dose [ | Indication that basal insulin is not enough includes: |
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]

Frequently asked questions and concerns
| Question | Answer |
|---|---|
| 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.). |
| Is there a ceiling to titration process? | There is no such thing as a maximum dose [ |
| What to do if daytime hypoglycemia occurs while on secretagogues? | Dose adjustment of secretatogue and/or basal insulin recommended |
| 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. |
| What to do if sickness occurs? | Normally continue with the usual dose of basal insulin |
| 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 |
| What to do if gave the dose twice? | Test more frequently |
| 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) |
| 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 |
| When to refer to a specialist? [ | Patient has frequent episodes of unexplained hypoglycemia |
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
| Anti-hyperglycemic agent | Anti-hyperglycemic agents when initiating basal insulin | Comments | |
|---|---|---|---|
| Metformin | Continued | – | |
| Insulin secretagogues | Options to continue, reduce, or stop the | If SU is stopped or reduced, titration of insulin is even more important | |
| TZDs | Usually discontinueda [ | Due to increased risk of edema and heart failure with insulin [ | |
| Incretin agents (GLP-1R agonist, DPP4i) | Continueda [ | – | |
| SGLT2 inhibitor | Continued | – | |
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®)
Box 2: panel recommendations for medical follow-up with diabetes HCPs [87, 91]
| When | What and why |
|---|---|
| 24–72 h | When initiating insulin or titration |
| 1–2 week(s) | Patients report BG readings |
| 1 month | Patients report BG readings |
| 3 months | A1C measurement |
| 6 months | A1C measurement |
| Within 24 h of hypoglycemia | Educate patient on recognizing, preventing, and treating hypoglycemia |