In some instances, patients will require medication reduction or discontinuation. 1):S98–S110 - August 01, 2020, http://www.diabetesjournals.org/content/license, http://www.fda.gov/Drugs/DrugSafety/ucm493244.htm, http://www.micromedexsolutions.com/micromedex2/4.34.0/WebHelp/RED_BOOK/Introduction_to_REDB_BOOK_Online.htm, https://data.medicaid.gov/Drug-Pricing-and-Payment/NADAC-National-Average-Drug-Acquisition-Cost-/a4y5-998d, 9. With the advent of improved continuous glucose monitors, closed-loop pump-sensor systems, and devices that offer alternative approaches for patients with hypoglycemia unawareness, the role of pancreas transplantation alone, as well as islet transplant, will need to be reconsidered. 9. Lifestyle modifications that improve health (see Section 5 “Facilitating Behavior Change and Well-being to Improve Health Outcomes,” https://doi.org/10.2337/dc20-S005) should be emphasized along with any pharmacologic therapy. 9.1). Longer-acting basal analogs (U-300 glargine or degludec) may convey a lower hypoglycemia risk compared with U-100 glargine when used in combination with oral agents (68–74). 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the TITRATE study, Pharmacokinetics and pharmacodynamics of insulin glargine given in the evening as compared with in the morning in type 2 diabetes, Dose-response effects of insulin glargine in type 2 diabetes, Efficacy and safety of insulin analogues for the management of diabetes mellitus: a meta-analysis, Long-acting insulin analogues versus NPH insulin (human isophane insulin) for type 2 diabetes mellitus, Long-acting insulin analogues versus NPH human insulin in type 2 diabetes: a meta-analysis, Patient-level meta-analysis of efficacy and hypoglycaemia in people with type 2 diabetes initiating insulin glargine 100U/mL or neutral protamine Hagedorn insulin analysed according to concomitant oral antidiabetes therapy, Insulin Glargine 4002 Study Investigators, The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients, A 26-week, randomized, parallel, treat-to-target trial comparing insulin detemir with NPH insulin as add-on therapy to oral glucose-lowering drugs in insulin-naive people with type 2 diabetes, Insulin glargine or NPH combined with metformin in type 2 diabetes: the LANMET study, on behalf of the EDITION 3 study investigators, 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), New insulin glargine 300 U/ml versus glargine 100 U/ml in Japanese people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs: glucose control and hypoglycaemia in a randomized controlled trial (EDITION JP 2), Glycaemic control and hypoglycaemia with new insulin glargine 300 U/ml versus insulin glargine 100 U/ml in people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs: the EDITION 2 randomized 12-month trial including 6-month extension, Efficacy and safety of degludec versus glargine in type 2 diabetes, Comparison of insulin degludec with insulin glargine in insulin-naive subjects with type 2 diabetes: a 2-year randomized, treat-to-target trial, Effect of insulin degludec vs insulin glargine U100 on hypoglycemia in patients with type 2 diabetes: the SWITCH 2 randomized clinical trial, NN1250-3579 (BEGIN Once Long) Trial Investigators, Insulin degludec versus insulin glargine in insulin-naive patients with type 2 diabetes: a 1-year, randomized, treat-to-target trial (BEGIN Once Long), Association of initiation of basal insulin analogs vs neutral protamine Hagedorn insulin with hypoglycemia-related emergency department visits or hospital admissions and with glycemic control in patients with type 2 diabetes, Insulin Access and Affordability Working Group, Short-acting insulin analogues vs. regular human insulin in type 2 diabetes: a meta-analysis, Meta-analysis of insulin aspart versus regular human insulin used in a basal-bolus regimen for the treatment of diabetes mellitus, Effect of total daily dose on efficacy, dosing, and safety of 2 dose titration regimens of human regular U500 insulin in severely insulin-resistant patients with type 2 diabetes, One-year sustained glycaemic control and less hypoglycaemia with new insulin glargine 300 U/ml compared with 100 U/ml in people with type 2 diabetes using basal plus meal-time insulin: the EDITION 1 12-month randomized trial, including 6-month extension, New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 2 diabetes using oral agents and basal insulin: glucose control and hypoglycemia in a 6-month randomized controlled trial (EDITION 2), Improved postprandial glucose with inhaled technosphere insulin compared with insulin aspart in patients with type 1 diabetes on multiple daily injections: the STAT study, Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes, Glucagon-like peptide-1 receptor agonist and basal insulin combination treatment for the management of type 2 diabetes: a systematic review and meta-analysis, Insulin and glucagon-like peptide 1 receptor agonist combination therapy in type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials, Treatment intensification with stepwise addition of prandial insulin aspart boluses compared with full basal-bolus therapy (FullSTEP Study): a randomised, treat-to-target clinical trial, Institutional Subscriptions and Site Licenses, Special Podcast Series: Therapeutic Inertia, Special Podcast Series: Influenza Podcasts, Addendum. A comparative effectiveness meta-analysis suggests that each new class of noninsulin agents added to initial therapy with metformin generally lowers A1C approximately 0.7–1.0% (46,47). 9. Chamberlain JJ, Kalyani RR, Leal S, Rhinehart AS, Shubrook JH, Skolnik N, Herman WH. Diabetes Care 2020;43(Suppl. Despite evidence for reduced hypoglycemia with newer, longer-acting basal insulin analogs in clinical trial settings, in practice these effects may be modest compared with NPH insulin (75). On the other hand, two doses of premixed insulin is a simple, convenient means of spreading insulin across the day. A 9.5 Once initiated, metformin should be continued as long as it is tolerated and not ... PHARMACOLOGIC APPROACHES TO GLYCEMIC TREATMENT U-300 glargine has a longer duration of action than U-100 glargine but modestly lower efficacy per unit administered (81,82). Pharmacologic approaches to the management of glycemia in patients with type 2 diabetes (T2D) are discussed in section 9. In addition, the American Diabetes Association position statement “Type 1 Diabetes Management Through the Life Span” provides a thorough overview of type 1 diabetes treatment (19). The subjects enrolled in the cardiovascular outcome trials using empagliflozin, canagliflozin, liraglutide, and semaglutide had A1C ≥7%, and more than 70% were taking metformin at baseline. These concentrated preparations may be more convenient and comfortable for patients to inject and may improve adherence in those with insulin resistance who require large doses of insulin. In trials comparing the addition of an injectable GLP-1 RAs or insulin in patients needing further glucose lowering, the efficacy of the two treatments was similar (50–52). B, 9.11 Intensification of treatment for patients with type 2 diabetes not meeting treatment goals should not be delayed. Many individuals with type 2 diabetes require doses of insulin before meals, in addition to basal insulin, to reach glycemic targets. Because insulin absorption from IM sites differs according to the activity of the muscle, inadvertent IM injection can lead to unpredictable insulin absorption and variable effects on glucose, with IM injection being associated with frequent and unexplained hypoglycemia in several reports. 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. © 2019 by the American Diabetes Association. Intensifying to injectable therapies. Treatment of Type 1 Diabetes: Synopsis of the 2017 American Diabetes Association Standards of Medical Care in Diabetes. Patients and/or caregivers should receive education about proper injection site rotation and to recognize and avoid areas of lipohypertrophy. The prandial insulin regimen can then be intensified based on patient needs (see Figure 9.2). (33). Davies MJ, D'Alessio DA, Fradkin J, et al. Exogenous-delivered insulin should be injected into subcutaneous tissue, not intramuscularly. Pharmacologic approaches to glycemic treatment: Standards of medical care in diabetes – 2020. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD), update to: management of hyperglycemia in type 2 diabetes, 2018: a consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). E. The American Diabetes Association/European Association for the Study of Diabetes consensus report “Management of Hyperglycemia in Type 2 Diabetes, 2018” and the 2019 update (33,34) recommend a patient-centered approach to choosing appropriate pharmacologic treatment of blood glucose (Fig. The ongoing Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) will compare four drug classes (sulfonylurea, DPP-4 inhibitor, GLP-1 receptor agonist, and basal insulin) when added to metformin therapy over 4 years on glycemic control and other medical, psychosocial, and health economic outcomes (28). Clipboard, Search History, and several other advanced features are temporarily unavailable. Although most patients prefer oral medications to drugs that need to be injected, the eventual need for the greater potency of injectable medications is common, particularly in people with a longer duration of diabetes. In this landmark trial, lower A1C with intensive control (7%) led to ∼50% reductions in microvascular complications over 6 years of treatment. E, 9.8 A patient-centered approach should be used to guide the choice of pharmacologic agents. The FDA has also approved a concentrated formulation of rapid-acting insulin lispro, U-200 (200 units/mL). Cardiovascular Disease and Risk Management Hypertension/Blood Pressure Control Lipid Management Antiplatelet Agents Cardiovascular Disease S124 11. Please enable it to take advantage of the complete set of features! Epub 2019 Aug 13. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes—2020. Recommendations cover oral and noninsulin injectable therapies, insulin treatment, and combination injectable therapies. Injectable and oral glucose-lowering drugs have been studied for their efficacy as adjuncts to insulin treatment of type 1 diabetes. PHARMACOLOGIC APPROACHES TO GLYCEMIC TREATMENT Rapid-acting inhaled insulin used be- foremealsintype1diabeteswasshown to be noninferior when compared with aspartinsulinforA1Clowering,withless hypoglycemia observed with inhaled in- sulin therapy (16). Recommendations have been published elsewhere outlining best practices for insulin injection (23). Suggested citation: American Diabetes Association. C. Because the hallmark of type 1 diabetes is absent or near-absent β-cell function, insulin treatment is essential for individuals with type 1 diabetes. See the section insulin injection technique above, for guidance on how to administer insulin safely and effectively. USA.gov. Rather, the utility and importance of insulin to maintain glycemic control once progression of the disease overcomes the effect of other agents should be emphasized. Diabetes Care 19 December 2019 [Epub ahead of print].DOI: 10.2337/dci19-0066, 10-year follow-up of intensive glucose control in type 2 diabetes, Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: a systematic review and meta-analysis, FDA Drug Safety Communication: FDA revises warnings regarding use of the diabetes medicine metformin in certain patients with reduced kidney function, Long-term treatment with metformin in type 2 diabetes and methylmalonic acid: post hoc analysis of a randomized controlled 4.3year trial, Diabetes Prevention Program Research Group, Long-term metformin use and vitamin B12 deficiency in the Diabetes Prevention Program Outcomes Study, Dapagliflozin, metformin XR, or both: initial pharmacotherapy for type 2 diabetes, a randomised controlled trial, Safe and simple emergency department discharge therapy for patients with type 2 diabetes mellitus and severe hyperglycemia, Clinical considerations for use of initial combination therapy in type 2 diabetes, Initial combination therapy with metformin, pioglitazone and exenatide is more effective than sequential add-on therapy in subjects with new-onset diabetes. As glucose toxicity resolves, simplifying the regimen and/or changing to oral agents is often possible. Proper insulin injection technique includes injecting into appropriate body areas, injection site rotation, appropriate care of injection sites to avoid infection or other complications, and avoidance of intramuscular (IM) insulin delivery. The risks and benefits of adjunctive agents continue to be evaluated, but only pramlintide is approved for treatment of type 1 diabetes. Recommended starting dose is 500mg daily with the evening meal, increasing as needed to achieve goals to a total dose of 2000mg per day (ADA, 2020). The committee selected and reviewed the studies, developed the recommendations, and solicited feedback from the larger clinical community. Reduction of nocturnal hypoglycemia in people with type 1 diabetes using insulin pumps with glucose sensors is improved by automatic suspension of insulin delivery at a preset glucose level (12–14). A, 9.6 Early combination therapy can be considered in some patients at treatment initiation to extend the time to treatment failure. Section 12 “Older Adults” (https://doi.org/10.2337/dc20-S012) and Section 13 “Children and Adolescents” (https://doi.org/10.2337/dc20-S013) have recommendations specific for older adults and for children and adolescents with type 2 diabetes, respectively; Section 10 “Cardiovascular Disease and Risk Management” (https://doi.org/10.2337/dc20-S010) and Section 11 “Microvascular Complications and Foot Care” (https://doi.org/10.2337/dc20-S011) have recommendations for the use of glucose-lowering drugs in the management of cardiovascular and renal disease, respectively. Classification. Pharmacologic Approaches to Glycemic Treatment Pharmacologic Therapy for Type 1 Diabetes Surgical Treatment for Type 1 Diabetes Pharmacologic Therapy for Type 2 Diabetes S103 10. For appropriate context, see Fig. However, there is no consensus to guide the choice of injection or pump therapy in a given patient, and research to guide this decision-making is needed (12). U-300 glargine and U-200 degludec are three and two times as concentrated as their U-100 formulations, and allow higher doses of basal insulin administration per volume used. 9. ObesityManagementfor the TreatmentofType2 Diabetes Assessment Diet, Physical Activity, and Behavioral Therapy Pharmacotherapy Metabolic Surgery S64 8. See page S101. © 2021 by the American Diabetes Association. Postprandial glucose excursions are best controlled by a well-timed injection of prandial insulin. However, intensive therapy was associated with a higher rate of severe hypoglycemia than conventional treatment (62 compared with 19 episodes per 100 patient-years of therapy). Drug-specific and patient factors to consider when selecting antihyperglycemic treatment in adults with type 2 diabetes. Epub 2015 Mar 13. Similarly, the addition of a sodium–glucose cotransporter 2 (SGLT2) inhibitor to insulin therapy has been associated with improvements in A1C and body weight when compared with insulin alone (30,31); however, SGLT2 inhibitor use in type 1 diabetes is associated with a two- to fourfold increase in ketoacidosis. However, high costs and tolerability issues are important barriers to the use of GLP-1 RAs. A discussion was added on access to analog insulins and how there are multiple approaches to insulin treatment, with the goal of keeping patients safe and avoiding diabetic ketoacidosis and significant hypo- … 9.2). Therefore, consideration of cost is an important component of effective management. ©2019 by the American Diabetes Association. Two different once-daily fixed-dual combination products containing basal insulin plus a GLP-1 RA are available: insulin glargine plus lixisenatide and insulin degludec plus liraglutide. Ann Pharmacother. Enter multiple addresses on separate lines or separate them with commas. The combination of basal insulin and GLP-1 RA has potent glucose-lowering actions and less weight gain and hypoglycemia compared with intensified insulin regimens (84–86). Considerations include cardiovascular comorbidities, hypoglycemia risk, impact on weight, cost, risk for side effects, and patient preferences (Table 9.2 and Figure 9.1). Diabetes Care 2020;43(Suppl. Compared with sulfonylureas, metformin as first-line therapy has beneficial effects on A1C, weight, and cardiovascular mortality (36); there is little systematic data available for other oral agents as initial therapy of type 2 diabetes. In clinical trials, long-acting basal analogs (U-100 glargine or detemir) have been demonstrated to reduce the risk of symptomatic and nocturnal hypoglycemia compared with NPH insulin (61–66), although these advantages are modest and may not persist (67). Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-- 2020. A, 9.3 Patients with type 1 diabetes should be trained to match prandial insulin doses to carbohydrate intake, premeal blood glucose, and anticipated physical activity. Pharmacologic Approaches to Glycemic Treatment of Type 2 Diabetes: Synopsis of the 2020 American Diabetes Association's Standards of Medical Care in Diabetes Clinical Guideline Ann Intern Med . The principal action of basal insulin is to restrain hepatic glucose production and limit hyperglycemia overnight and between meals (59,60). These results have not been generalized to oral agents other than vildagliptin, but they suggest that more intensive early treatment has some benefits and should be considered through a shared decision-making process with patients, as appropriate. Diabetes Care, 43 (Supplement 1), S98-S110. Diabetes Care, 43 (Supplement 1), S98-S110. In patients with contraindications or intolerance to metformin, initial therapy should be based on patient factors; consider a drug from another class depicted in Fig. More information is available at http://www.diabetesjournals.org/content/license. This site needs JavaScript to work properly. 1): S73-S85 Learning Objectives •Recognize drug-specific and patient factors of antihyperglycemic agents to support patient-provider shared decision making Sign In to Email Alerts with your Email Address. Human regular insulin, NPH, and 70/30 NPH/regular products can be purchased for considerably less than the AWP and NADAC prices listed in Table 9.3 at select pharmacies. 2019 Sep 17;171(6):415-420. doi: 10.7326/M19-1638. The addition of metformin to adults with type 1 diabetes caused small reductions in body weight and lipid levels but did not improve A1C (27,28). For example, instruction of patients in self-titration of insulin doses based on self-monitoring of blood glucose improves glycemic control in patients with type 2 diabetes initiating insulin (58). However, over the past three decades, evidence has accumulated supporting more intensive insulin replacement, using multiple daily injections of insulin or continuous subcutaneous administration through an insulin pump, as providing the best combination of effectiveness and safety for people with type 1 diabetes. Pramlintide is based on the naturally occurring β-cell peptide amylin and is approved for use in adults with type 1 diabetes. As referenced above, there are now numerous evidence-based insulin delivery recommendations that have been published. Once a basal/bolus insulin regimen is initiated, dose titration is important, with adjustments made in both mealtime and basal insulins based on the blood glucose levels and an understanding of the pharmacodynamic profile of each formulation (pattern control). Pharmacologic Approaches to Glycemic Treatment–2020 and 10. Pharmacologic Approaches to Glycemic Treatment: NCI CPTC Antibody Characterization Program. Diabetes Care. Glycemic Targets Assessment of Glycemic Control A1C Testing A1C Goals Hypoglycemia Intercurrent Illness S57 7. Diabetes Care 2018; 41 (Suppl. 1.2 Align approaches to diabetes management with the Chronic Care Model (CCM). For patients without established ASCVD, indicators of high ASCVD risk, HF, or CKD, the choice of a second agent to add to metformin is not yet guided by empiric evidence. Figure 9.2 outlines these options, as well as recommendations for further intensification, if needed, to achieve glycemic goals. Methods: Over the last 25 years, rapid-acting and long-acting insulin analogs have been developed that have distinct pharmacokinetics compared with recombinant human insulins: basal insulin analogs have longer duration of action with flatter, more constant plasma concentrations and activity profiles than NPH insulin; rapid-acting analogs (RAA) have a quicker onset and peak and shorter duration of action than regular human insulin. To approach this variability in people using insulin treatment, strategies have evolved to adjust prandial doses based on predicted needs. Despite the advantages of insulin analogs in patients with type 1 diabetes, for some patients the expense and/or intensity of treatment required for their use is prohibitive. 4.1. In addition to hyperglycemia, insulinopenia can contribute to other metabolic disturbances like hypertriglyceridemia and ketoacidosis as well as tissue catabolism that can be life threatening. The ADA has developed and provided diabetes care stand-ards, guidelines and related doc-uments since 1989, and its clini-cal practice recommendations are integral resources for health care professionals. Section 9. 2017 Oct 3;167(7):493-498. doi: 10.7326/M17-1259. For individuals in whom carbohydrate counting is effective, estimates of the fat and protein content of meals can be incorporated into their prandial dosing for added benefit (22). ASCVD, atherosclerotic cardiovascular disease; CKD, chronic kidney disease; CV, cardiovascular; CVD, cardiovascular disease; CVOTs, cardiovascular outcomes trials; DPP-4i, dipeptidyl peptidase 4 inhibitor; eGFR, estimated glomerular filtration rate; GLP-1 RA, glucagon-like peptide 1 receptor agonist; HF, heart failure; SGLT2i, sodium–glucose cotransporter 2 inhibitor; SU, sulfonylurea; TZD, thiazolidinedione. For patients with established ASCVD or indicators of high ASCVD risk (such as patients ≥55 years of age with coronary, carotid, or lower-extremity artery stenosis >50% or left ventricular hypertrophy), established kidney disease, or heart failure, an SGLT-2 inhibitor or GLP-1 RA with demonstrated CVD benefit (Table 9.1, Table 10.3B, Table 10.3C) is recommended as part of the glucose-lowering regimen independent of A1C and in consideration of patient-specific factors (Figure 9.1). 8. Pharmacologic Therapy for Type 2 Diabetes: Synopsis of the 2017 American Diabetes Association Standards of Medical Care in Diabetes. Of note, prices listed are average wholesale prices (AWP) (54) and National Average Drug Acquisition Costs (NADAC) (55), separate measures to allow for a comparison of drug prices but do not account for discounts, rebates, or other price adjustments often involved in prescription sales that affect the actual cost incurred by the patient. Created Date: Inhaled insulin is contraindicated in patients with chronic lung disease, such as asthma and chronic obstructive pulmonary disease, and is not recommended in patients who smoke or who recently stopped smoking. Pharmacologic approaches to glycemic treatment: Standards of Medical Care in Diabetes—2020. Treatment ” in the complete 2020 Standards of Care for. In addition, recent evidence supports the utility of GLP-1 RAs in patients not reaching glycemic targets with use of non-GLP-1 RA oral agent regimens. Total daily insulin requirements can be estimated based on weight, with typical doses ranging from 0.4 to 1.0 units/kg/day. HHS Retrieved from ndards_of_Care_2020.pdf Drugs.com. Inhaled human insulin has a rapid peak and shortened duration of action compared with RAA and may cause less hypoglycemia and weight gain (7), and faster-acting insulin aspart may reduce prandial excursions better than RAA (8); further investigation is needed to establish a clear place for these agents in diabetes management. Severe metabolic decompensation can be, and was, mostly prevented with once or twice daily injections for the six or seven decades after the discovery of insulin. Section 12 “Older Adults”(https://doi.org/10.2337/dc20-S012) has a full discussion of treatment considerations in older adults, a setting where changes of glycemic goals and de-escalation of therapy is common.