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Diabetes prevalence continues to rise in the United States, affecting more than 30 million people (9.4% of the population) in 2015 (1). Diabetes is expensive in terms of both direct medical costs and indirect costs of disability, lost work productivity, and premature death. The estimated cost of diabetes in the United States was $245 billion in 2012 (2). Optimizing care by facilitating glycemic control, patient education, preventive health screenings, and adherence to the treatment regimen have been suggested as methods to decrease the cost of this disease (3). There are inequalities in the disease burden of diabetes in the United States. The prevalence, incidence, and complications rates of diabetes are higher in non-Hispanic black, Hispanic, and American Indian/Alaska Native populations (4,5). Minority, low-income, and uninsured people have a higher risk for omissions of recommended diabetes prevention services (6). Furthermore, people who are non-English–speaking may experience barriers to effective diabetes medication management, including prohibitive costs of medications, hindered communication, knowledge deficits, and difficulties in understanding (7). The American Diabetes Association consistently identifies the promotion of health equity for populations disparately affected by diabetes as an advocacy priority (8). Federally Qualified Health Centers (FQHCs) provide primary care, behavioral health services, dental care, and other health care services to medically underserved populations. These safety-net clinics work to reduce barriers to health and health care in low-income populations disproportionately affected by chronic disease by increasing access to health care providers and medications (9,10). In 2016, FQHCs provided care to more than 26 million patients, more than half of whom had an income below the federal poverty level. The Health Resources and Services Administration (HRSA) reported in its 2016 health center data report that 32.1% of the more than 2 million patients with diabetes receiving care at FQHCs had …

Diabetes is a major worldwide epidemic with >415 million individuals living with the disease. This number is expected to grow to a staggering 642 million by 2040 (1). According to the American Diabetes Association, diabetes affects 29.1 million Americans, or 9.3% of the population. Diabetes management in the United States presents several challenges: 20% of individuals with diabetes remain undiagnosed, 1.4 million new cases are diagnosed annually, and one-third of adults with diabetes are not at the general recommended A1C goal of

Diabetes is a complex, chronic medical condition affecting 29.1 million people in the United States (9.3% of the population) and is projected to affect one in three Americans by 2050 if the current trend continues (1). Diabetes management can be challenging, often requiring multiple therapeutic agents as the disease progresses. Current guidelines recommend metformin as first-line pharmacological therapy for the treatment of type 2 diabetes. Multiple second-line options are available for patients whose A1C goal is not achieved with monotherapy, and selection should be based on patient- and drug-specific factors. Sodium–glucose cotransporter 2 (SGLT2) inhibitors, the newest U.S. Food and Drug Administration (FDA)–approved oral antidiabetic agents, are among these options for patients with type 2 diabetes. Canagliflozin, dapagliflozin, and empagliflozin are the currently available SGLT2 inhibitors in the United States (2,3). Sodium–glucose cotransporter 1 (SGLT1) is predominantly located in the small intestine, but is also expressed in the kidneys, trachea, heart, and colon (4,5). In the kidneys, SGLT1 is primarily located in the S3 segment of the proximal convoluted tubule (PCT) (4). SGLT2 is expressed in the kidneys and primarily located in the S1 and S2 segments of the PCT (4,5). In normoglycemic adults, about 180 g of glucose (Figure 1) is filtered per day in the glomerulus, and most is reabsorbed (4,6). In people with diabetes, reabsorption of glucose is increased compared to people without diabetes (7,8). SGLT1 and SGLT2 are located in the apical membrane and facilitate the transport of glucose with sodium from the renal tubular lumen into the cells (Figure 2) (4). FIGURE 1. Structures of glucose, phlorizin, canagliflozin, dapagliflozin, and empagliflozin. FIGURE 2. Cotransport of glucose and sodium by SGLT1 and SGLT2 in the PCT. Phlorizin (Figure 1), an O -glucose derivative/ O -glycoside, was discovered in …

There are 29.1 million people in the United States living with diabetes (1). Except in cases with contraindications, annual influenza vaccination is recommended for all people with diabetes to reduce morbidity, mortality, and health care costs associated with influenza illness (2,3). There were 12 influenza vaccines available for the 2016–2017 influenza season. These vaccines were categorized into inactivated or live, quadrivalent or trivalent, and high-dose or standard-dose formulations (2). Common adverse reactions of pain, soreness, fever, muscle aches, fatigue, redness, or swelling may occur after intramuscular vaccine administration (4). Hyperglycemia is not noted as an adverse reaction in vaccine package inserts; however, reports of its occurrence have been documented in the Vaccine Adverse Event Reporting System (VAERS) (5). Since 1991, there have been 946 reports of hyperglycemia with all available vaccines and 361 reports of hyperglycemia with all types of influenza vaccines. When looking specifically at the trivalent influenza vaccine, there have been 235 reported cases, with 70.6% reported during the first 4 days after vaccine administration (5). In light of these reports, a literature search was performed to obtain more information about acute hyperglycemia after vaccine administration. The search was performed with the advanced search option in PubMed using the terms "hyperglycemia,” “blood sugar,” “blood glucose,” “vaccines,” “influenza vaccine,” “diabetes,” and “immunizations.” The search failed to yield any literature reports specifically related to blood glucose …

Just a few years shy of a century ago, a group of Canadian researchers discovered a viable method of extracting insulin, filling a large and critical gap in the therapeutic treatment of diabetes (1). Since then, insulin and its associated delivery devices have become an integral part of the care and management of patients living with diabetes. Shortly after the first insulin injection was successfully delivered, vials of insulin became available commercially. At this time, large glass syringes were used to administer insulin, and each injection required sterilization of the syringe, as well as sharpening of the syringe needle with a pumice stone. Through the years, insulin syringes modernized, but it was not until the 1970s that an alternate delivery system—the insulin pump, used in continuous subcutaneous insulin infusion (CSII) regimens—became available. Fifteen years later, the first insulin pen was introduced to the marketplace, providing evidence that, as time progresses, there is no shortage of innovation in the diabetes arena. The first two rapid-acting inhaled insulins on the market—Exubera in 2006 and Afrezza in 2014—represented yet another innovation milestone. In theory, inhaled insulin completely eliminated the psychological barriers associated with subcutaneous insulin delivery, such as needle phobia and incorrect injection technique. However, in October 2007, Pfizer withdrew Exubera from the market, and in January 2016, Sanofi withdrew from a $925 million marketing agreement with MannKind for Afrezza; both removals were due to poor sales volume. Although patients and providers have been searching for years for alternatives to injecting insulin, Exubera has already failed, and Afrezza’s destiny is uncertain. In 2006, Exubera was the first inhaled insulin approved by the U.S. Food and Drug Administration (FDA). It showed noninferiority in efficacy with regard to A1C lowering in both type 1 diabetes (2) and type 2 diabetes (3) compared to mixed regular/NPH …

The association between inpatient hyperglycemia and adverse patient outcomes is well documented.1–7 Thus, focus on inpatient glycemic control has increased in the past decade. However, optimal glycemic targets remain controversial, and significant barriers to optimal glycemic control persist. After publication of the initial van den Berghe trial in surgical intensive care patients,1 several professional organizations published guidelines supporting near-normal glycemic targets.8,9 Subsequent trials documented an increased risk for hypoglycemia with tight glycemic control, suggesting that more modest glycemic targets may be optimal.10–13 The Normoglycemia in Intensive Care Evaluation–Survival Using Glucose Algorithm Regulation (NICE-SUGAR) study,14 a large, randomized trial involving > 6,100 medical and surgical patients, documented higher 90-day mortality rates in patients managed with tight glycemic control than in those receiving conventional glucose management. Although hypoglycemia was more common among patients in the intensive treatment group, the association of hypoglycemia with an increased hazard ratio for death was similar in the two groups, suggesting that hypoglycemia contributed to the excess mortality in the intensively treated group.15 The increased risk for hypoglycemia and mortality with tight glycemic control does not justify ignoring glycemic control, but it does justify setting more moderate targets. The American Diabetes Association (ADA), the American Association of Clinical Endocrinologists (AACE), the Surviving Sepsis Campaign, and the Institute for Healthcare Improvement all updated their guidelines for glycemic control in 2009 in response to data from NICE-SUGAR.16–18 All four sets of guidelines recommend initiating insulin therapy in patients with persistent hyperglycemia (blood glucose > 180 mg/dl). After insulin is initiated, the target blood glucose range should be 140–180 mg/dl for the majority of patients. However, a more stringent goal of 110–140 mg/dl may be appropriate for certain patients, provided it can be achieved without …

Glucagon-like peptide-1 (GLP-1) receptor agonists are safe and effective U.S. Food and Drug Administration (FDA)-approved drug products for use in the treatment of type 2 diabetes. To date, the FDA has approved five GLP-1 receptor agonist parenteral formulations: exenatide, liraglutide, exenatide extended-release, and, most recently, albiglutide and dulaglutide. All of these formulations are administered subcutaneously. Exenatide and liraglutide are administered twice daily and once daily, respectively. Until recent approvals of albiglutide and dulaglutide, exenatide extended-release was the only formulation approved for once-weekly use. Relative to other antidiabetic pharmacotherapies, such as metformin or sulfonylureas, GLP-1 receptor agonists are not widely used drugs. A recent study of the usage patterns of antidiabetic drugs estimate that, of 16,316,580 patients prescribed a noninsulin antidiabetic drug in 2012, GLP-1 receptor agonists were dispensed to 673,367 (4.1%) (1). Exenatide extended-release is formulated to encapsulate exenatide in poly-(D,L-lactide-co-glycolide) (also known as PLG matrix) microspheres, which release the active drug over a sustained time interval (2). PLG is a biodegradable and biocompatible medical polymer with an established safety profile used as a controlled release excipient in a variety of drug products (3). PLG undergoes hydrolysis into lactic and glycolic acids, which are eventually eliminated as carbon dioxide and water. In 2012, the introduction of exenatide extended-release into the U.S. market offered GLP-1 receptor agonist users the advantage of fewer injections per week. At the time of approval, the FDA was aware of small, largely asymptomatic injection-site nodules that were associated with exenatide extended-release use. Based on the microsphere excipient, injection-site nodules could be expected with exenatide extended-release administration. However, these reactions were considered nonserious and believed to resolve quickly. Based on controlled data provided in the U.S. approved prescribing information, injection-site reactions were observed more frequently in exenatide extended-release users (17.1%) than in those using exenatide (12.7%) …

Current treatment of type 2 diabetes begins with diet and lifestyle modifications accompanied by use of oral antihyperglycemic medications. Despite multiple therapeutic options for people with type 2 diabetes, the disorder continues to progress, resulting in the gradual deterioration of glycemic control over time (1). This is the result of insulin resistance and progressive decline in β-cell function, combined with increased hepatic glucose output as a result of glucagon dysregulation (2). These factors lead to elevations in both fasting and prandial glucose levels. It is well known that poor glycemic control is associated with increased risk of microvascular and macrovascular complications. Ultimately, basal insulin, premixed insulin, and/or prandial insulin are added to the treatment regimen (3). The U.K. Prospective Diabetes Study and its follow-up found that patients with uncontrolled type 2 diabetes receiving intensive insulin therapy had significantly lower risks of microvascular and macrovascular complications, as well as lowered mortality rates compared to diabetes patients on standard therapy (1,4). However, intensive insulin therapy is associated with weight gain and hypoglycemia (1). A plethora of other treatment options are available for diabetes patients, many of which are either weight neutral or promote weight loss. The downside of having these additional treatment options is that the wide range of choices may present a challenge to prescribers when determining the optimal therapeutic regimen. In making these decisions, health care providers should consider patients’ disease progression state, comorbidities, and concomitant treatments (5). GLP-1 receptor agonists are one of the newer drug classes to appear on the market. These agents have been proven to be effective without increased risk of hypoglycemia or weight gain (6,7). They are ideal for patients who have had episodes of hypoglycemia on large insulin doses and for obese patients who could benefit from the …

As currently diagnosed, gestational diabetes mellitus (GDM) affects 5–9% of all pregnancies in the United States and is growing in prevalence.1 It is defined as carbohydrate intolerance of variable severity that is first recognized during pregnancy. Although GDM has been recognized for decades, the potential significance of the condition, as well as criteria for screening and diagnosis, remain debatable.1 Historically, GDM has been treated with lifestyle modifications and insulin, and oral antihyperglycemic agents have been used infrequently because of concerns regarding neonatal hypoglycemia and teratogenicity. Most recent studies suggest that oral hypoglycemic agents, specifically metformin, are safe to use during pregnancy (Table 1).2–13 Risk for developing GDM has been noted in women who are overweight before pregnancy, have had GDM in a previous pregnancy, or have a family history of diabetes. Poorer outcomes have been seen in both pregnant women and their developing fetuses, including induction of labor and caesarean delivery in women and death, shoulder dystocia, bone fracture, and nerve palsy in fetuses.1 Moreover, recent studies show that diagnosis and management of this disorder will have beneficial effects on both maternal and neonatal outcomes.14,15 According to the American College of Obstetrics and Gynecology, comprehensive screening techniques have been implemented by > 90% of practices in the United States.16 Reasons for the implementation of screening programs were developed from the evidence obtained in the Hyperglycemia and Adverse Pregnancy Outcomes study.17 This large, prospective, observational study found possible adverse effects associated with even mild maternal hyperglycemia. It included a cohort of women with glucose levels at the upper end of the normal range, as well as women with mild GDM. The investigators found a linear correlation between higher levels of maternal glucose and adverse outcomes, including increased birth weight, …