Coinciding with National Diabetes Month is the recent publication, 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), which contains the most up-to-date, impactful set of new treatment guidelines for patients with Type 2 diabetes mellitus (T2DM).
This article summarizes the highlights of the report, which was developed by experts from both the ADA and the EASD and has been referred to as a “paradigm shift” toward a more focused and patient-centered approach to select a comprehensive treatment program for the management of T2DM and its chronic complications.
The role of glucose control in T2DM
Historically, there were only a few medication classes available for the treatment of T2DM. They were typically centered around glucose control, which is universally recognized as fundamental to diabetes management, given that elevated blood sugar has been extensively proven to cause the “microvascular” complications of diabetes affecting the kidneys, eyes and peripheral nerves.
The drugs that have been the standard T2DM treatments for decades for glucose control include injectable insulins, and oral sulfonylureas and metformin. However, sulfonylureas and insulin can cause troublesome low blood sugar reactions (hypoglycemia), and can often lead to weight gain – exacerbating the obesity that already burdens many T2DM patients.
In addition, despite use of these medications, many T2DM patients still have not achieved their recommended glucose goals, spurring the need for new medications that were durable and could lower glucose to target levels – without the side effects of hypoglycemia or weight gain. This unmet medical need has fostered intensive research efforts at pharmaceutical companies over the past 10-20 years.
Exploring benefits beyond glucose control
While pharmaceutical companies were researching these new mechanisms, they were also strategizing for potential drug benefits beyond glucose control. Then, in 2008, the FDA mandated that prior to marketing approval, any new medications for T2DM needed to be tested in large clinical trials to rule out the possibility that they exacerbated the risk for cardiovascular disease, which is the most frequent cause of morbidity and mortality in patients with T2DM.
This mandate for more extensive research trials led to unexpected results. Not only had the subsequent trials demonstrated cardiovascular safety, but, in fact, pharmaceutical companies also discovered and developed several new classes of drugs for T2DM. These available drugs have been shown to go beyond glucose control, offering the potential for less hypoglycemia and actual weight loss as well as unique benefits to ameliorate known complications of T2DM, including kidney impairment, cardiovascular disease (heart attacks and stroke) and heart failure. These characteristics are described in the new consensus report.
The consensus report’s patient-centered recommendations for choosing among specific classes of T2DM treatments is guided by assessing an individual’s:
Making use of new data available from many carefully controlled clinical trials, in particular the cardiovascular outcomes trials over the past four years, the consensus report details its recommendations in new treatment algorithms, outlining therapies and medications to help achieve optimal diabetes control and also improve quality of life.
This patient-centered approach takes into account the individual’s health history and preferences and builds on the core tenets of T2DM care: comprehensive lifestyle management, diabetes self-management education and the use of prescription medications.
Over the disease management continuum of T2DM, the patient remains at the center. This approach incorporates considerations for lifestyle interventions such as medical nutrition therapy and physical activity to control weight, along with the possibility to modify these interventions and medications, based on shifts in the patient’s life and circumstances.
Understanding widely used treatment options
Metformin, a generic drug that has long been recommended as first-line oral therapy for T2DM, remains as the preferred initial therapy as it is recognized for its effectiveness in glucose-lowering without causing hypoglycemia or weight gain. Nevertheless, the majority of patients are not able to reach their glucose goals with metformin therapy alone, and typically require various combination therapies while continuing metformin.
New injectable drugs, known as GLP-1 receptor agonists, have been widely used in the past several years and data from the recent clinical trials have supported their earlier use, e.g., prior to insulin when an injectable is considered. GLP-1 agents promote insulin secretion when glucose levels are high, but given that this stimulation of insulin in the body is dependent on elevated glucose levels, this occurs without the risk of hypoglycemia. GLP-1 agents also generally result in meaningful levels of weight loss.
More recent clinical trial data have now shown that the GLP-1s can provide cardiovascular benefits as well. Both daily and weekly versions of the GLP-1s are available for injection, offering additional choices for administration to patients.
The benefits of newer agents
One of the newest classes of drugs for T2DM is the sodium-glucose cotransporter-2 inhibitors (SGLT2i). These interesting oral medications promote the loss of excess glucose in the urine, which lowers blood glucose without causing hypoglycemia. Along with increased urine glucose, excretion of salt and water tends to lower blood pressure, and the loss of glucose calories from the body by this mechanism can promote weight loss. While the SGLT2is are generally well-tolerated, the increased glucose in the urine can be associated with manageable genital yeast infections.
Recent clinical trials with SGLT2i agents have demonstrated a beneficial effect on renal function in patients with chronic renal impairment, supporting their early use in this population. In addition, advantages for T2DM patients with underlying cardiovascular disease have been demonstrated with the SGLT2is, supporting their earlier use in patients to reduce cardiovascular mortality and episodes of congestive heart failure.
Raising the bar for comprehensive T2DM care
Overall, these new recommendations provide an updated framework to enable physicians and other diabetes care providers to work together with their patients to select an approach that promotes successful long-term management of their diabetes.
This data-driven consensus report will go a long way to help physicians use the newer drugs advantageously on their patients where particular benefits have been demonstrated in controlled trials, especially in the primary care setting where the vast majority of T2DM care is provided. The emphasis on various medical and socioeconomic factors will also promote better regimen adherence. Further iterations of these guidelines will likely appear in the future when updated clinical information emerges from ongoing studies.
The impact of these analyses and recommendations will be to raise the bar for new therapies seeking to go beyond lowering glucose levels. This challenge will be valuable to patients in the future as new drugs and combination regimens continue to emerge for the control of T2DM, while offering additional benefits in preventing or reversing the devastating chronic complications of this globally epidemic disease.
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Davies, MJ et al., 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). Diabetes Care 2018 https://doi.org/10.2337/dci18-0033
Graphic adapted from Davies, MJ et al., 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). Diabetes Care 2018 https://doi.org/10.2337/dci18-0033