Type 2 diabetes in the US managed care setting: the burden of disease and rationale for an oral glucagon-like peptide-1 receptor agonist.

Diabetes affects an estimated 34 million US adults, with type 2 diabetes (T2D) accounting for 90% to 95% of cases. The downstream consequences of uncontrolled T2D are substantial, including an increased risk of microvascular complications (eg, renal impairment, retinopathy, and peripheral neuropathy), cardiovascular disease, impaired quality of life, and death. Overall, diabetes places a significant strain on the US health care system, with 7.8 million hospitalizations annually among patients with diabetes, and $237 billion in direct medical costs. Injectable glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been available for T2D for over a decade, and are recommended, in particular, for patients with a compelling need to minimize hypoglycemia risk, curtail weight gain, or promote weight loss, and for patients with established cardiovascular disease. Despite being associated with high glucose-lowering efficacy, weight loss, and a low risk of hypoglycemia, injectable GLP-1RAs are relatively underutilized, and are associated with suboptimal adherence and persistence. These challenges may relate in part to the injectable route of administration, given that injection-related concerns have been linked with a failure to intensify T2D therapy in a timely manner (ie, therapeutic inertia), and are cited by patients as a barrier to initiating and persisting with injectable treatments. The approval of the first tablet formulation of a GLP-1RA for T2D, oral semaglutide, has the potential to address these challenges. In this context, we review the burden of T2D in the United States, the role of GLP-1RAs, the challenges of therapeutic inertia and poor adherence, and the rationale for an oral GLP-1RA, focusing on considerations for managed care.

Burden of Illness in Type 2 Diabetes Mellitus.

An estimated 30.2 million Americans have diabetes, and this number is expected to increase based on trends over recent decades and compounded by an aging U.S. POPULATION: As reviewed in this article, type 2 diabetes mellitus (T2DM) is associated with impaired health-related quality of life (HRQoL) and with a substantial socioeconomic burden. Compared with individuals without T2DM, those with T2DM have worse HRQoL, greater decrements in HRQoL over time, and possibly greater depressive symptomology. Diabetes-related complications and comorbidities (e.g., obesity and cardiovascular disease) are associated with worse HRQoL. Hypoglycemic episodes are associated with reduced HRQoL and greater levels of depression; they can also interfere with social and occupational activities. In turn, low HRQoL can be a driver for poor glycemic control. In 2012, the total estimated cost associated with diagnosed diabetes in the United States was $245 billion. Factors contributing to increased health care resource utilization and costs in patients with T2DM include medical comorbidities, diabetes-related complications, inadequate glycemic control, and hypoglycemic episodes. Readmission is a key driver of hospital-related costs and is more common among elderly patients with T2DM. Elderly patients with T2DM represent a particularly vulnerable population given that these patients may have varying degrees of physical and mental comorbidities that can increase their risk of hypoglycemia, falls, and depression. This review demonstrates that T2DM imposes a considerable burden on both the individual and society. Treatment strategies should consider the effects of treatment on HRQoL and on outcomes (e.g., complications and hypoglycemia) that affect both HRQoL and costs. Management strategies that maximize HRQoL while minimizing the risk of hypoglycemia and other treatment-related complications are particularly critical in the elderly. DISCLOSURES: This supplement was funded by Novo Nordisk. Cannon reports speaker fees and owns stock in Novo Nordisk. Handelsman reports research grants from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Grifols, Janssen, Lexicon, Merck, Novo Nordisk, Regeneron, and Sanofi; speaker fees from Amarin, Amgen, AstraZeneca, Boehringer Ingelheim-Lilly, Janssen, Merck, Novo Nordisk, Regeneron, and Sanofi; and has served in advisory capacity to Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Eisai, Intarcia, Janssen, Lilly, Merck, Merck-Pfizer, Novo Nordisk, Regeneron, and Sanofi. Heile reports speaker fees from and has served as advisor to Novo Nordisk. Shannon reports consultant and speaker fees from Novo Nordisk and Boehringer Ingelheim-Lilly Alliance.

Cardiovascular Outcomes with Once-Weekly GLP-1 RAs: Clinical and Economic Implications.

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of atherosclerotic cardiovascular (ASCVD) disease, which is the largest contributor to the economic burden of diabetes. Minimization of disease morbidity through comprehensive management of ASCVD risk factors, including but not limited to hyperglycemia, is a key goal of T2DM therapy. Emerging evidence with some glucagon-like peptide-1 receptor agonists (GLP-1 RAs) points to beneficial effects across a range of atherosclerotic risk factors and possible improvement of some cardiovascular outcomes independent of these effects. Given these benefits, there has been substantial interest in evaluating the cardiovascular safety of GLP-1 RAs as well as their potential to reduce the risk of major adverse cardiac events (MACE). Following the superior clinical outcome with the once-daily GLP-1 RA liraglutide (Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results [LEADER]), this review examines and summarizes the effects of once-weekly GLP-1 RAs, including exenatide extended release (ER), dulaglutide, and semaglutide, on reducing cardiovascular events in patients with T2DM. A phase 3 cardiovascular outcomes trial (EXSCEL) of exenatide ER found no significant difference between exenatide ER and placebo in reducing MACE in patients with T2DM. In a phase 3 premarketing trial in T2DM patients at high risk of cardiovascular disease (SUSTAIN-6), semaglutide significantly reduced the risks of MACE and non-fatal stroke compared with placebo. A phase 3 study (REWIND) is underway to evaluate the effects of dulaglutide on MACE. Considering the substantial costs of cardiovascular disease in patients with T2DM, it will be of interest to assess the impact of treatment with once-weekly GLP-1 RAs on cardiovascular disease-related costs among patients with T2DM. DISCLOSURES: This supplement was funded by Novo Nordisk. Heile reports speaker fees from and has served as advisor to Novo Nordisk. Billings reports personal fees from Dexcom, Novo Nordisk, and Sanofi. Cannon reports speaker fees and owns stock in Novo Nordisk. Handelsman reports research grants from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Grifols, Janssen, Lexicon, Merck, Novo Nordisk, Regeneron, and Sanofi; speaker fees from Amarin, Amgen, AstraZeneca, Boehringer Ingelheim-Lilly, Janssen, Merck, Novo Nordisk, Regeneron, and Sanofi; and has served in advisory capacity to Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Eisai, Intarcia, Janssen, Lilly, Merck, Merck-Pfizer, Novo Nordisk, Regeneron, and Sanofi. Shannon reports consultant and speaker fees from Novo Nordisk and Boehringer Ingelheim-Lilly Alliance. Wyne has nothing to disclose.