Glycemic Management in Adults with Type 1 Diabetes 2018 Clinical Practice Guidelines Glycemic Management in Adults with Type 1 Diabetes Chapter 12 Angela McGibbon MD PhD FRCPC FACP, Lenley Adams MD FRCPC FACP, Karen Ingersoll RN CDE, Tina Kader MD FRCPC, Barna Tugwell MD FRCPC

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In memoriam … Dr. Angela McGibbon Angie completed her MD, residency in Internal Medicine and fellowship in Endocrinology at Dalhousie University before returning to her hometown, Fredericton in 2003.  She was a Clinical Associate Professor of Medicine (Endocrinology) at Memorial and Dalhousie Universities and was active in regional and provincial diabetes strategies and all levels of medication education.  She was known for her warmth, compassion and dedication to her family, her patients and her community. She passed away from a sudden illness on February 11, 2018. She will be missed.

Key Changes Formerly titled “Pharmacotherapy in Type 1 diabetes” 2018 Diabetes Canada CPG – Chapter 12. Glycemic Management in Adults with Type 1 Diabetes Key Changes 2018 Formerly titled “Pharmacotherapy in Type 1 diabetes” New title to reflect other treatment modalities for type 1 diabetes New information on New bolus (prandial) and basal insulin preparations Role of CSII and CGM CGM, continuous glucose monitoring; CSII, continuous subcutaneous insulin infusion

Pharmacotherapy in Type 1 Diabetes Checklist 2018 Diabetes Canada CPG – Chapter 12. Glycemic Management in Adults with Type 1 Diabetes Pharmacotherapy in Type 1 Diabetes Checklist USE basal-bolus injection therapy or continuous subcutaneous insulin infusion TAILOR insulin regimens to the individual’s treatment goals, lifestyle, diet, age, general health, motivation, hypoglycemia awareness status, and ability for self-management COUNSEL about the risk, prevention and treatment of insulin-induced hypoglycemia 5

Analogue Basal Serum Insulin Level 2018 Diabetes Canada CPG – Chapter 12. Glycemic Management in Adults with Type 1 Diabetes Serum Insulin Level Time Analogue Bolus Human Basal Analogue Basal Human Bolus guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca 6

Types of insulin Insulin type (trade name) Onset Peak Duration BOLUS (prandial or mealtime) insulins Rapid-acting insulin analogues (clear) Insulin aspart (NovoRapid®) Insulin glulisine (Apidra®) Insulin lispro (Humalog®) U-100 U-200 Faster-acting insulin aspart (Fiasp®) 9–20min 10–15min 4min 1–1.5h 1–2h 0.5-1.5h 3–5h 3.5–5h 3–4.75h 3-5h Short-acting insulins (clear) Insulin regular (Humulin®-R, Novolin® ge Toronto) Insulin regular U-500 (Entuzity® (U-500) 30min 15min 2–3h 4-8h 6.5h 17-24h BASAL insulins Intermediate-acting (cloudy) Insulin neutral protamine Hagedorn (Humulin® N, Novolin® ge NPH) 1–3h 5–8h Up to 18h Long-acting insulin (clear) Insulin detemir (Levemir®) Insulin glargine U-100 (Lantus®) Insulin glargine U-300 (Toujeo®) Insulin glargine biosimilar (Basaglar®) Insulin degludec U-100, U-200 (Tresiba®) 90min Not applicable U-100 glargine 24h, detemir 16–24h U-300 glargine >30h degludec 42h PREMIXED insulins Premixed regular insulin –NPH (cloudy) Humulin® 30/70 Novolin® ge 30/70, 40/60, 50/50 A single vial or cartridge contains a fixed ratio of insulin (% of rapid-acting or short-acting insulin to % of intermediate-acting insulin) Premixed insulin analogues (cloudy) Biphasic insulin aspart (NovoMix® 30) Insulin lispro/lispro protamine (Humalog® Mix25 and Mix50)

Insulin Therapy in Type 1 Diabetes 2018 Diabetes Canada CPG – Chapter 12. Glycemic Management in Adults with Type 1 Diabetes Insulin Therapy in Type 1 Diabetes BASAL – BOLUS INJECTION THERAPY Bolus insulin at meal times + basal insulin once or twice a day OR CONTINUOUS SUBCUTANEOUS INSULIN INFUSION “insulin pump therapy” with continuous subcutaneous infusion of insulin via a catheter 8

Must Counsel About Hypoglycemia 2018 Diabetes Canada CPG – Chapter 12. Glycemic Management in Adults with Type 1 Diabetes Must Counsel About Hypoglycemia Must counsel all patients with type 1 diabetes about hypoglycemia: recognition, treatment, prevention Assess risk factors for severe hypoglycemia Assess for hypoglycemia unawareness and treat accordingly 9

Benefits of Continuous Subcutaneous Insulin Infusion (CSII) 2018 Diabetes Canada CPG – Chapter 12. Glycemic Management in Adults with Type 1 Diabetes Benefits of Continuous Subcutaneous Insulin Infusion (CSII) For individuals using basal bolus injections (BBI), changing to CSII provides Small improvement in A1C Improved treatment satisfaction and diabetes specific related QOL Reduction in severe hypoglycemia if there is a high baseline rate of severe hypoglycemia (non-severe and nocturnal hypoglycemia unchanged) BBI, basal-bolus insulin; CSII, continuous subcutaneous insulin infusion; QOL, quality of life Yeh HC et al. Ann Intern Med 2012;157:336-47. Pickup JC et al. Diabet Med 2008;25:765-74.

Benefits of Continuous Glucose Monitoring (CGM) 2018 Diabetes Canada CPG – Chapter 12. Glycemic Management in Adults with Type 1 Diabetes Benefits of Continuous Glucose Monitoring (CGM) If using BBI or CSII with SMBG, adding CGM with high sensor adherence provides Improvement in A1C with no increase in hypoglycemia Improvement in QOL, diabetes distress, fear of hypoglycemia If using sensor-augmented pump (SAP) therapy with nocturnal hypoglycemia, using SAP with low glucose suspend provides Reduction in nocturnal hypoglycemia with no A1C increase BBI, basal-bolus insulin; CSII, continuous subcutaneous insulin infusion; CGM, continuous glucose monitoring; SMBG, self-monitoring of blood glucose; SAP, sensor augmented pump; QOL, quality of life Bergenstal RM et al. N Engl J Med 2010;363:311-20. Bergenstal RM et al. N Engl J Med 2013;368:224-32.

Adjunctive therapy in type 1 diabetes 2018 Diabetes Canada CPG – Chapter 12. Glycemic Management in Adults with Type 1 Diabetes Adjunctive therapy in type 1 diabetes Metformin, SGLT2 inhibitors (dapagliflozin, empagliflozin, sotagliflozin), GLP-1 receptor agonist (liraglutide) have been studied Metformin did not provide sustained metabolic or CV benefits SGLT2 inhibitors demonstrated some metabolic benefits but risk of DKA needs to be better understood Liraglutide also showed some metabolic benefits but there are no current indications for use in type 1 diabetes NO recommendation for adjunctive therapy CV, cardiovascular; DKA, diabetic ketoacidosis

2018 Diabetes Canada CPG – Chapter 12 2018 Diabetes Canada CPG – Chapter 12. Glycemic Management in Adults with Type 1 Diabetes Recommendations 1-2 In adults with type 1 diabetes, basal-bolus injection therapy or CSII as part of an intensive diabetes management regimen should be used to achieve glycemic targets [Grade A, Level 1A] In adults with type 1 diabetes using basal-bolus injection therapy or CSII, rapid-acting insulin analogues should be used in place of regular insulin to improve A1C and to minimize the risk of hypoglycemia  [Grade B, Level 2 for basal-bolus injection therapy; Grade B, Level 2 for lispro in CSII; Grade B, Level 2 for aspart in CSII, Grade D, Consensus for glulisine in CSII] and to achieve postprandial BG targets [Grade B, Level 2 for basal-bolus injection therapy; Grade B, Level 2 for CSII] BG; blood glucose; CSII, continuous subcutaneous insulin infusion

2018 Diabetes Canada CPG – Chapter 12 2018 Diabetes Canada CPG – Chapter 12. Glycemic Management in Adults with Type 1 Diabetes Recommendation 3 2018 In adults with type 1 diabetes on basal-bolus injection therapy, A long-acting insulin analogue may be used in place of NPH to reduce the risk of hypoglycemia [Grade B, Level 2 for detemir; Grade B, Level 2 for glargine U-100; Grade D, Consensus for degludec and glargine U-300], including nocturnal hypoglycemia [Grade B, Level 2 for detemir; Grade B, Level 2 for glargine U-100; Grade D Consensus for degludec, and glargine U-300]   Degludec may be used instead of detemir or glargine U-100 to reduce nocturnal hypoglycemia [Grade B, Level 2] compared to detemir; Grade C, Level 3 compared to glargine U-100]

2018 Diabetes Canada CPG – Chapter 12 2018 Diabetes Canada CPG – Chapter 12. Glycemic Management in Adults with Type 1 Diabetes Recommendation 4 4. All individuals with type 1 diabetes and their support persons should be counselled about the risk and prevention of hypoglycemia, and risk factors for severe hypoglycemia should be identified and addressed [Grade D, Consensus]

2018 Diabetes Canada CPG – Chapter 12 2018 Diabetes Canada CPG – Chapter 12. Glycemic Management in Adults with Type 1 Diabetes Recommendation 5 2018 In adults with type 1 diabetes and hypoglycemia unawareness, the following nonpharmacological strategies may be used to reduce the risk of hypoglycemia: A standardized education program targeting rigorous avoidance of hypoglycemia while maintaining overall glycemic control [Grade A, Level 1A] Increased frequency of SMBG, including periodic assessment during sleeping hours [Grade D, Consensus] CGM with high sensor adherence in those using CSII [Grade C, Level 3] Less stringent glycemic targets with avoidance of hypoglycemia for up to 3 months [Grade C, Level 3] CGM, continuous glucose monitoring; CSII, continuous subcutaneous insulin infusion; SMBG, self-monitoring of blood glucose

2018 Diabetes Canada CPG – Chapter 12 2018 Diabetes Canada CPG – Chapter 12. Glycemic Management in Adults with Type 1 Diabetes Recommendation 6 2018 6. In adults with type 1 diabetes on basal-bolus injection therapy who are not achieving glycemic targets, CSII with or without CGM may be used to improve A1C [Grade B, Level 2 with CGM; Grade B, Level 2 without CGM] CGM, continuous glucose monitoring; CSII, continuous subcutaneous insulin infusion

Recommendation 7 In adults with type 1 diabetes, 2018 Diabetes Canada CPG – Chapter 12. Glycemic Management in Adults with Type 1 Diabetes Recommendation 7 2018 In adults with type 1 diabetes, CSII may be used instead of basal-bolus injection therapy to improve treatment satisfaction [Grade C, Level 3] CSII plus CGM may be used instead of basal-bolus injection therapy or CSII with SMBG to improve quality of life, treatment satisfaction and other health-quality-related outcomes [Grade B, Level 2] CGM, continuous glucose monitoring; CSII, continuous subcutaneous insulin infusion; SMBG, self-monitoring of blood glucose

2018 Diabetes Canada CPG – Chapter 12 2018 Diabetes Canada CPG – Chapter 12. Glycemic Management in Adults with Type 1 Diabetes Recommendations 8-9 2018 Adults with type 1 diabetes on CSII should undergo periodic evaluation to determine whether continued CSII is appropriate [Grade D, Consensus]  9. In adults with type 1 diabetes and an A1C at or above target regardless of insulin delivery method used, CGM with high sensor adherence may be used to improve or maintain A1C [Grade B, Level 2] without increasing hypoglycemia [Grade C, Level 3] CGM, continuous glucose monitoring; CSII, continuous subcutaneous insulin infusion

2018 Diabetes Canada CPG – Chapter 12 2018 Diabetes Canada CPG – Chapter 12. Glycemic Management in Adults with Type 1 Diabetes Recommendation 10 2018 10. In adults with type 1 diabetes experiencing nocturnal hypoglycemia and using CSII and CGM, SAP with low glucose suspend may be chosen over SAP alone to reduce hypoglycemia [Grade B, Level 2] CGM, continuous glucose monitoring; CSII, continuous subcutaneous insulin infusion; SAP, sensor augmented pump

2018 Diabetes Canada CPG – Chapter 12 2018 Diabetes Canada CPG – Chapter 12. Glycemic Management in Adults with Type 1 Diabetes Key Messages Basal-bolus insulin routines (i.e., multiple daily injections or continuous subcutaneous insulin infusion) are the preferred insulin management regimens for adults with type 1 diabetes Insulin regimens should be tailored to the individual’s treatment goals, lifestyle, diet, age, general health, motivation, hypoglycemia awareness status and ability for self-management All individuals with type 1 diabetes should be counselled about the risk, prevention and treatment of hypoglycemia. Avoidance of nocturnal hypoglycemia may include changes in insulin therapy and increased monitoring

2018 Diabetes Canada CPG – Chapter 12 2018 Diabetes Canada CPG – Chapter 12. Glycemic Management in Adults with Type 1 Diabetes Key Messages If glycemic targets are not met with optimized multiple daily injections, CSII may be considered. Successful CSII therapy requires appropriate candidate selection, ongoing support and frequent involvement with the health-care team CGM may be offered to people not meeting their glycemic targets, who will wear the devices the majority of the time, in order to improve glycemic control CGM, continuous glucose monitoring; CSII, continuous subcutaneous insulin infusion

Key Messages for People with Diabetes 2018 Diabetes Canada CPG – Chapter 12. Glycemic Management in Adults with Type 1 Diabetes Key Messages for People with Diabetes Insulin therapy is required for the treatment of type 1 diabetes There are a variety of insulins and methods of giving insulin to help manage type 1 diabetes Insulin is injected by pen, syringe or insulin pump

Key Messages for People with Diabetes 2018 Diabetes Canada CPG – Chapter 12. Glycemic Management in Adults with Type 1 Diabetes Key Messages for People with Diabetes Your health-care provider will work with you to determine such things as: The number of insulin injections you need per day The timing of your insulin injections The dose of insulin you need with each injection If an insulin pump is appropriate for you Your pump settings if you are using a pump

Key Messages for People with Diabetes 2018 Diabetes Canada CPG – Chapter 12. Glycemic Management in Adults with Type 1 Diabetes Key Messages for People with Diabetes The insulin treatment your health-care provider prescribes will depend on your goals, lifestyle, meal plan, age, and general health. Social and financial factors may also be taken into account Learning to avoid and treat hypoglycemia (low blood glucose) is an important part of your education. The ideal balance is to achieve blood glucose levels that are as close to target as possible while avoiding hypoglycemia

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