disease (CKD), defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.732 m 2 should receive medication with proven kidney benefit from the SGLT2 inhibitors class. Decisions about initial medication, additional medication, or a change in medication because of not meeting glycemic goals or new comorbidities should not be delayed. The choice of medication(s) to minimize cardiorenal risk and weight gain and to optimize glycemic management is based on guidelines, glycemic goals, comorbidities, risk of side effects, patient clinical characteristics and preferences, and access (Davies et al., 2022). Figures 2 and 3 identify pharmacologic approaches to manage adults with type 2 diabetes when the goal is to achieve glycemic control and weight loss along with cardiorenal risk reduction. Healthcare Professional Consideration: Diabetes self- management education and support (DSMES) is a central aspect of care for people with type 2 diabetes in concert with pharmacologic therapy involving several antihyperglycemic agents and dosing algorithms. Evidence has consistently shown that DSMES improves knowledge, glycemic levels, and clinical and psychological measures, and it reduces hospitalization admissions (Davis et al., 2022). DSMES is tailored to the individual, including their beliefs and preferences. DSMES is provided using multiple approaches and in a variety of settings. Critical times to refer patients to DSMES are at the time of diagnosis, annually or when not meeting treatment targets, when complications develop, and when transitions in life and care occur (Powers et al., 2020). In all instances, the National Standards for DSMES define diabetes self-management as a collaborative and ongoing process intended to facilitate the development of knowledge, skills, and attitudes required for successful self-management (Davis et al., 2022).
Figure 1: Factors Influencing Person-Centered Glycemic Management in Patients with Type 2 Diabetes
Note. Adapted from Davies et al., 2022 Pharmacological therapy is tailored to patient comorbidities, patient-centered treatment factors, and management needs (ElSayed et al., 2023a; White, 2022). Important comorbidities to consider include atherosclerotic heart disease (ASCVD), chronic kidney disease (CKD), and heart failure (HF). Several categories of medications are used to manage hyperglycemia in adults with type 2 diabetes. Treatment options have changed considerably over the past several years and include a variety of medications. This course will provide an overview of noninsulin antihyperglycemics agents and noninsulin injectables along with best evidence regarding the choice of medication to consider. For all patients with type 2 diabetes, it is essential to assess whether atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), chronic kidney disease (CKD), or obesity are present, as this will impact the choice of drug therapy (ElSayed et al., 2023a; Odegard & Capoccia, 2022). All patients with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) should be prescribed medication with proven cardiovascular benefit from the GLP-1 RA class or SGLT2 inhibitor class. In addition, all patients with type 2 diabetes and chronic kidney
Evidence-Based Practice There is clear evidence of benefit for cardiovascular and kidney outcomes in large-scale randomized trials where sodium–glucose cotransporter-2 (SGLT2) inhibitors are administered with or without metformin (Neuen et al., 2021). SGLT2 inhibitors are now recommended as the preferred second-line therapy in people who do not achieve sufficient glucose control on metformin alone, particularly for those with cardiovascular comorbidities like heart failure or chronic kidney disease (Davies et al., 2022).
BIGUANIDES
The history of metformin can be traced back to the 1920s, when the active ingredient, galegine, was introduced as a potential glucose-lowering agent. However, galegine was found to have weak hypoglycemic effects and an association with lactic acidosis in persons without risk factors for acidosis. In response to the introduction of sulfonylureas in the 1950s, two synthetic derivatives of galegine, metformin and phenformin, were introduced into clinical practice by the 1970s. Phenformin was taken off the market because of its toxic effects and association with lactic acidosis (Rena et al., 2017). Metformin continues to be a popular medication for treating type 2 diabetes, both as a monotherapy and in combination with other medications. Based on the 2023 American Diabetes Association (ADA) Standards of Care for patients with type 2 diabetes, metformin and other more efficacious drugs can be used as first-line therapy or with other drugs depending on the degree of glycemic lowering needed (ElSayed et al., 2023a). Because
of metformin’s general efficacy, absence of weight gain, hypoglycemia, general tolerability, and low cost, it is a popular antihyperglycemic agent (ElSayed et al., 2023a). However, GLP-1 and GIP/GLP-1 drugs are first line for weight management, as they are more efficacious than metformin in meeting this goal. In addition, metformin is initiated concurrently with lifestyle interventions at the time of diagnosis and can be effective as monotherapy or in combination with other glucose-lowering medication (see Figure 2). If a patient’s A1C is greater than 10% or their blood glucose levels are >300 mg/dL, 2023 ADA standards of care recommend higher-efficacy approaches to achieve glycemic goals. For example, additional high-efficacy medications like glucagon-like peptide-1 receptor agonists (GLP-1 RA), a combination of noninsulin therapy and injectables, or starting insulin should be considered (ElSayed et al., 2023b; Odegard & Capoccia, 2022). Very-high-efficacy GLP-1 RAs include dulaglutide (high dose) and semaglutide.
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