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8. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes—2018

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8. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes—2018 Diabetes Care Volume 41, Supplement 1, January 2018 S73 8. Pharmacologic Approaches to American Diabetes Association Glycemic Treatment: Standards of Medical Care in Diabetesd2018 Diabetes Care 2018;41(Suppl. 1):S73–S85 | https://doi.org/10.2337/dc18-S008 8. PHARMACOLOGIC APPROACHES TO GLYCEMIC TREATMENT The American Diabetes Association (ADA) “Standards of Medical Care in Diabetes” includes ADA’s current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA’s clinical practice recommendations, please refer to the Standards of Care Introduction. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC. PHARMACOLOGIC THERAPY FOR TYPE 1 DIABETES Recommendations c Most people with type 1 diabetes should be treated with multiple daily in- jections of prandial insulin and basal insulin or continuous subcutaneous insulin infusion. A c Most individuals with type 1 diabetes should use rapid-acting insulin analogs to reduce hypoglycemia risk. A c Consider educating individuals with type 1 diabetes on matching prandial insulin doses to carbohydrate intake, premeal blood glucose levels, and anticipated physical activity. E c Individuals with type 1 diabetes who have been successfully using continuous subcutaneous insulin infusion should have continued access to this therapy after they turn 65 years of age. E Insulin Therapy Insulin is the mainstay of therapy for individuals with type 1 diabetes. Generally, the starting insulin dose is based on weight, with doses ranging from 0.4 to Suggested citation: American Diabetes Associ- 1.0 units/kg/day of total insulin with higher amounts required during puberty. ation. 8. Pharmacologic approaches to glyce- The American Diabetes Association/JDRF Type 1 Diabetes Sourcebook notes mic treatment: Standards of Medical Care in 0.5 units/kg/day as a typical starting dose in patients with type 1 diabetes who Diabetesd2018. Diabetes Care 2018;41(Suppl. 1): are metabolically stable, with higher weight-based dosing required immediately S73–S85 following presentation with ketoacidosis (1), and provides detailed information © 2017 by the American Diabetes Association. on intensification of therapy to meet individualized needs. The American Diabetes Readers may use this article as long as the work “ is properly cited, the use is educational and not Association (ADA) position statement Type 1 Diabetes Management Through for profit, and the work is not altered. More infor- theLifeSpan” additionally provides a thorough overview of type 1 diabetes mation is available at http://www.diabetesjournals treatment (2). .org/content/license. S74 Pharmacologic Approaches to Glycemic Treatment Diabetes Care Volume 41, Supplement 1, January 2018 Education regarding matching prandial compared with U-100 glargine in patients placebo (23). The Reducing With Metformin insulin dosing to carbohydrate intake, with type 1 diabetes (19,20). Vascular Adverse Lesions in Type 1 Diabetes premeal glucose levels, and anticipated Rapid-acting inhaled insulin used be- (REMOVAL) trial investigated the addition activity should be considered, and se- fore meals in patients with type 1 diabe- of metformin therapy to titrated insulin lected individuals who have mastered tes was shown to be noninferior when therapy in adults with type 1 diabetes at carbohydrate counting should be edu- compared with aspart insulin for A1C low- increased risk for cardiovascular disease cated on fat and protein gram estimation ering, with less hypoglycemia observed and found that metformin did not signifi- (3–5). Although most studies of multiple with inhaled insulin therapy (21). How- cantly improve glycemic control beyond daily injections versus continuous subcu- ever, the mean reduction in A1C was the first 3 months of treatment and that taneous insulin infusion (CSII) have been greater with aspart (–0.21% vs. –0.40%, progression of atherosclerosis (measured small and of short duration, a systematic satisfying the noninferiority margin of by carotid artery intima-media thickness) review and meta-analysis concluded that 0.4%), and more patients in the insulin was not significantly reduced, although there are minimal differences between aspart group achieved A1C goals of other cardiovascular risk factors such as the two forms of intensive insulin therapy #7.0% (53 mmol/mol) and #6.5% (48 body weight and LDL cholesterol im- in A1C (combined mean between-group mmol/mol). Because inhaled insulin car- proved (24). Metformin is not FDA- difference favoring insulin pump therapy tridges are only available in 4-, 8-, and approved for use in patients with type 1 –0.30% [95% CI –0.58 to –0.02]) and se- 12-unit doses, limited dosing increments diabetes. vere hypoglycemia rates in children and to fine-tune prandial insulin doses in type 1 Incretin-Based Therapies adults (6). A 3-month randomized trial in diabetes are a potential limitation. Due to their potential protection of b-cell patients with type 1 diabetes with noctur- Postprandial glucose excursions may mass and suppression of glucagon release, nal hypoglycemia reported that sensor- be better controlled by adjusting the tim- glucagon-like peptide 1 (GLP-1) receptor augmented insulin pump therapy with ing of prandial (bolus) insulin dose admin- agonists (25) and dipeptidyl peptidase the threshold suspend feature reduced istration. The optimal time to administer 4 (DPP-4) inhibitors (26) are being studied nocturnal hypoglycemia without increas- prandial insulin varies, based on the type in patients with type 1 diabetes but are ing glycated hemoglobin levels (7). The of insulin used (regular, rapid-acting ana- not currently FDA-approved for use in pa- U.S. Food and Drug Administration (FDA) log, inhaled, etc.), measured blood glucose tients with type 1 diabetes. has also approved the first hybrid closed- level, timing of meals, and carbohydrate loop system pump. The safety and effi- consumption. Recommendations for pran- Sodium–Glucose Cotransporter 2 Inhibitors cacy of hybrid closed-loop systems has dial insulin dose administration should Sodium–glucose cotransporter 2 (SGLT2) been supported in the literature in ado- therefore be individualized. inhibitors provide insulin-independent lescents and adults with type 1 diabetes glucose lowering by blocking glucose re- (8,9). Pramlintide absorption in the proximal renal tubule by Intensive management using CSII and Pramlintide, an amylin analog, is an agent inhibiting SGLT2. These agents provide continuous glucose monitoring should be that delays gastric emptying, blunts pan- modest weight loss and blood pressure encouragedinselectedpatientswhen creatic secretion of glucagon, and en- reduction in type 2 diabetes. There are there is active patient/family participa- hances satiety. It is FDA-approved for use three FDA-approved agents for patients tion (10–12). in adults with type 1 diabetes. It has been with type 2 diabetes, but none are FDA- The Diabetes Control and Complica- shown to induce weight loss and lower in- approved for the treatment of patients tions Trial (DCCT) clearly showed that in- sulin doses. Concurrent reduction of pran- with type 1 diabetes (2). SGLT2 inhibitors tensive therapy with multiple daily dial insulin dosing is required to reduce the may have glycemic benefits in patients injections or CSII delivered by multidisci- risk of severe hypoglycemia. with type 1 or type 2 diabetes on insulin plinary teams of physicians, nurses, dieti- therapy (27). The FDA issued a warning tians, and behavioral scientists improved Investigational Agents about the risk of ketoacidosis occurring glycemia and resulted in better long-term Metformin in the absence of significant hyperglyce- outcomes (13–15). The study was carried Adding metformin to insulin therapy may mia (euglycemic diabetic ketoacidosis) out with short-acting and intermediate- reduce insulin requirements and improve in patients with type 1 or type 2 diabe- acting human insulins. Despite better mi- metabolic control in patients with type 1 tes treated with SGLT2 inhibitors. crovascular, macrovascular, and all-cause diabetes. In one study, metformin was Symptoms of ketoacidosis include dysp- mortality outcomes, intensive therapy found to reduce insulin requirements nea, nausea, vomiting, and abdominal was associated with a high rate of severe (6.6 units/day, P , 0.001), and led to pain. Patients should be instructed to hypoglycemia (61 episodes per 100 patient- small reductions in weight and total and stop taking SGLT2 inhibitors and seek years of therapy). Since the DCCT, a number LDL cholesterol but not to improved gly- medical attention immediately if they of rapid-acting and long-acting insulin an- cemic control (absolute A1C reduction have symptoms or signs of ketoacidosis alogs have been developed. These analogs 0.11%, P 5 0.42) (22). A randomized clin- (28). are associated with less hypoglycemia, ical trial similarly found that, among over- less weight gain, and lower A1C than human weight adolescents with type 1 diabetes, SURGICAL TREATMENT FOR insulins in people with type 1 diabetes the addition of metformin to insulin did TYPE 1 DIABETES (16–18).
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