Adult Type 2 Diabetes Insulin Guidelines INTRODUCTION Background pharmacists, nurses, and dietitians from across Sutter Health. This More than 29 million American adults have diabetes, which is the 4th revision of the original guideline first written in 2008. is approximately 9.1% of adults in the United States. Diabetes This guideline is based on a primary review of the literature. doubles the risk of heart disease and strokes.3 Uncontrolled The identification and rating of the literature to support this diabetes is the leading cause of adult-onset blindness, kidney Adult Type 2 Diabetes Insulin Guideline followed a multi-step disease and lower-limb amputations.3 There has been an process. Pertinent articles for review were identified by a Medline substantial increase in the prevalence of diabetes. Over the last search including the key words: Diabetes Mellitus, Type 2/drug 30 years the number of patients with diabetes has quadrupled. If therapy, Hypoglycemic Agents, Insulin, Algorithms, Titrat,* the prevalence continues to increase, one out of every three adults Bolus and Basal. The search was limited to 2005 to June 1st 2016, will have diabetes by 2050.4 Despite the increase in prevalence language English, and Adult 19+. Older clinical trials evaluating of diabetes, the clinical management of diabetes has improved Human Regular insulin were included, since none were available over time. The mean A1C has improved from 1999 to 2010 from from 2005-2016. The guideline team then reviewed the list of 7.6% to 7.2% which has led to an improvement in cardiovascular articles and included those that were identified as clinical trials disease outcomes and a substantial decrease in the number of examining the initiation and titration of insulin in an ambulatory patients with end stage microvascular complications. That said, setting in adults. The most recent American Diabetes Association only 33-49% of patients with diabetes currently have their diabetes (ADA) and American Association of Clinical Endocrinologists targets for blood glucose, blood pressure and lipid control at goal, (AACE) consensus guidelines, the most recent American Family and only 14% have all three targets at goal.1 Medicine review summary, and the most recent ADA position Approximately 5-10% of diabetes is type 1 diabetes. 90-95% of statements and technical reviews on diabetes care topics were also diabetes is type 2 diabetes.3 Type 1 diabetes is due to insulin included. Insulin package insert recommendations were obtained deficiency, and must be treated with insulin. Type 2 diabetes is from Lexi-Comp, Online. The recommendations for this guideline initially due to insulin resistance, but relative insulin deficiency are based on the information from these articles above. develops over time. Many patients with type 2 diabetes The insulin guideline is intended for adults with type 2 diabetes eventually need to take insulin to manage their condition. in an ambulatory setting. It is not intended for patients with This clinical practice guideline is written to support clinicians type 1 diabetes, patients with ketosis or acute insulin deficiency, who care for patients with type 2 diabetes using insulin. pregnant patients, hospitalized patients, children or adolescents. It is intended to help clinicians, educators, care managers and Clinical Practice Guidelines Benefit patients make decisions about insulin, oral, and non-insulin A clinical practice guideline (CPG) can help improve consistency injectable diabetes medications according to standard clinical of best practice care in a health care organization. It allows all practice. It should not take the place of clinical decision-making members of a care team to screen, diagnosis, monitor, treat and skills of individual clinicians. All decisions should be made within educate patients using standard recommendations. It also allows the context of the specific situation for each patient, including an organization to measure clinical outcomes in the population current health, current medications, risk of hypoglycemia, quality using metrics consistent with the CPG treatment algorithm. It of life, life expectancy, and patient preference. provides a template to translate the organization’s diagnosis and This guideline is divided into the following sections: treatment recommendations into embedded decision support General recommendations . 2 tools within the electronic health record and into patient-friendly Basal insulin . 4 information and handouts. It provides a means to efficiently adjust care consistently across the organization when new evidence Prandial insulin . 6 emerges about disease management in the health care literature. Premixed insulin . 8 Switching back and forth from analog to human insulins . .9 Sutter Health Adult Type 2 Diabetes Switching back and forth from basal/prandial to Insulin Guidelines premixed insulin . 10 The following Sutter Health Adult Type 2 Diabetes Insulin Pre-operative insulin recommendations . 11 Clinical Practice Guideline was written by a multi-disciplinary Additional information . 12 team including internists, family physicians, endocrinologists, Adult Type 2 Diabetes Insulin Guidelines General Recommendations For type 2 diabetes patients with A1C and glucose levels above goal despite optimal use of other oral diabetes medications, consider Glucagon-like Peptide-1 Receptor Agonists (GLP1 RAs) or insulin.1 GLP1 RAs can be equally or more effective than insulin, and are associated with less weight gain and less hypoglycemia.1,5,15,19,22,26,30 Consider GLP1 RAs for patients who desire weight loss, have no contraindications to GLP RAs and who do not have signs or symptoms of severe hyperglycemia, significant insulin deficiency, or history of diabetic ketoacidosis (DKA). GLP1 RAs include below • Exenatide (Byetta®) • Exenatide ER (Bydureon®) • Liraglutide (Victoza®) • Dulaglutide (Trulicity®) • Albiglutide (Tanzeum®) Insulin is ideal for patients who have evidence of significant hyperglycemia, a history of DKA, need to avoid weight loss, have contraindications to GLP1 RAs, and/or cannot tolerate GLP1 RAs. • Start with BASAL INSULIN and follow initiation and titration guidelines below for most type 2 diabetes adult patients.1,5 • Consider start with FULL INSULIN REPLACEMENT (simultaneous basal and prandial insulin at physiologic doses) for patients with suspected type 1 diabetes, acute very high blood sugars, severe symptoms (polyuria, polydipsia, weight loss), evidence of ketoacidosis, or suspicion of severe insulin deficiency—in collaboration with a specialized diabetes provider. Note: all patients should have additional diabetes education when starting injectable or insulin medications1 Note: two basal Insulin and GLP1RAs combinations are FDA approved for once daily injection: • Soliqua™ 100/33 (insulin glargine 100 Units/mL & lixisenatide 33 mcg/mL injection) • Xultophy® 100/3.6 (degludec 100 units/mL and liraglutide 3.6 mg/mL injection) Rev. May, 2017 Adult Type 2 Diabetes Insulin Guidelines | 2 17-SYSCOM-0008379 Consider the following goals when adjusting medications:1 ADA A1C Goals*: • A1C < 7.0% is general goal • A1C < 8.0% goal may be appropriate if: Longstanding diabetes Limited life expectancy Known CVD or advanced complications Extensive co-morbid conditions Difficult to control despite use of insulin Severe hypoglycemia *Alternate A1C goals may be suggested based on individualized characteristics1,5,6 ADA Glucose Goals—Individualized based on characteristics above (especially if high risk for hypoglycemia):1,5,6 Fasting and pre-meal glucose • For most people: 80-130 mg/dL* • For older adults consider 1. If healthy: 90-130 mg/dL 2. If complex/intermediate health status (ie. multiple chronic conditions): 90-150 mg/dL 3. If very complex/poor health status (ie. end stage chronic conditions): 90-180 mg/dL Peak post-meal glucose (1-2 hours after meal) • < 180 mg/dL • Difference between pre-meal and post-meal glucose < 50 mg/dL Adult Type 2 Diabetes Insulin Guidelines | 3 BASAL INSULIN: Long-acting: Glargine 100 units/ml (Lantus,® Basaglar®) Glargine 300 units/ml (Toujeo®) Detemir 100 units/ml (Levemir®) Degludec 100 units/ml or 200 units/ml (Tresiba®) Intermediate-acting: NPH 100 units/ml NPH insulin has elevated risk of hypoglycemia so use with extra caution 1,5,8,24,27,32,35,49,56 INSTRUCTIONS: Basal insulin is the best starting insulin choice for most patients (if fasting glucose is above goal).1,5,8 Start one of the intermediate-acting or long-acting insulins listed above.1,8 Basal insulin is usually started at night and given once daily.20,27,31,33,34,39,43,44,45,51,52,55,57,61 If patient is on only basal insulin, then in general patient should eat predictable carb consistent meal size at regular intervals. Basal insulin should be given at the same time daily, except for Degludec which is equally effective if taken at variable times during the day.46 Continuing non-insulin anti-diabetes medications when starting basal insulin helps maintain glucose control60 but may increase risk of hypoglycemia.1,7,8 The decision about using each particular medication in combination with basal insulin should be individualized.7 Note: if NPH causes nocturnal hypoglycemia, consider switching NPH to long-acting insulin.5,32,49,56, 63 Key characteristics of diabetes medications when used with basal insulin: Metformin: Prevents weight gain and should be continued if tolerated.1,5,8 Sulfonylureas: Increases risk of hypoglycemia and weight gain.5,8,38,56 Meglitinides (ie Prandin®, Starlix®): Target