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Anti-hyperglycemic drug selection, sequence for type 2 diabetes addressed in ADA/EASD position statement update
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A revised position statement on the management of hypoglycemia in patients with type 2 diabetes, updated upon request from the American Diabetes Association and the European Association for the Study of Diabetes, is published in Diabetes Care.
The writing group that penned the guidelines published in 2012, when a paucity of comparative effectiveness research existed on the long-term treatment outcomes of anti-hyperglycemic drugs, reconvened from June to September 2014 to incorporate data from recent clinical trials.
“An entirely new statement was felt to be unnecessary,” according to the writing group. “Instead, the group focused on those areas where revisions were suggested by a changing evidence base.”
Silvio E. Inzucchi, MD, of Yale University School of Medicine, New Haven, Connecticut, with co-chair David R. Matthews, MD, University of Oxford, United Kingdom steered members’ input to address critical areas, including glycemic targets, therapeutic options, implementation strategies, other considerations and future directions.
Silvio E. Inzucchi
The experts emphasized that studies have determined that reducing hyperglycemia decreased both the onset and progression of macrovascular complications, but they noted that the impact of glucose control on cardiovascular complications remains uncertain and stressed the importance of an individualized approach.
“Instead of a one-size-fits-all approach, personalization is necessary, balancing the benefits of glycemic control with its potential risks, taking into account the adverse effects of glucose-lowering medications (particularly hypoglycemia), and the patient’s age and health status, among other concerns,” they wrote.
The researchers noted that the availability of sodium glucose cotransporter 2 (SGLT2) inhibitors presents a major change in treatment options since the previous publication. They underscored that earlier concerns about thiazolidinediones (TZD) and bladder cancer have been allayed; however, they advised that dipeptidyl peptidase-4 (DPP-4) inhibitors be used cautiously in light of potential cardiovascular effects and highlighted the pancreatic safety concerns in this class as well as in glucagon-like peptide-1 (GLP-1) receptor agonists.
“The use of any drug in patients with type 2 diabetes must balance the glucose-lowering efficacy,
side-effect profiles, anticipation of additional benefits, cost and other practical aspects of care, such as dosing schedule and requirements for glucose monitoring,” they wrote.
The experts highlighted recent calls to relax prescribing policies to extend the use of metformin — still the first-line choice for monotherapy — in patients with mild to moderate kidney disease, and encouraged due caution for renal insufficiency when considering second-line agents.
In addressing dual and triple combination therapies, the researchers noted that no evidence-based recommendation can be made for using SGLT2 inhibitors in conjunction with GLP-1 receptor agonists without data. Although clinicians can look to additional drugs to treat patients with HbA1c levels well above target ≥9% (≥75 mmol/mol), no proven advantage has been shown by achieving a glycemic target more quickly, according to the writing group.
“As long as close patient follow-up can be ensured, prompt sequential therapy is a reasonable alternative, even in those with baseline HbA1c levels in this range,” they wrote.
Basal insulin is still encouraged as part of the treatment approach for patients who do not reach agreed HbA1c targets; however, adding GLP-1 receptor agonists offers efficacy similar or superior to prandial insulin, along with weight loss and lower hypoglycemia.
“The available data now suggest that either a GLP-1 receptor agonist or prandial insulin could be used in this setting, with the former arguably safer, at least for short-term outcomes,” the researchers wrote. The first option may be more attractive in patients with obesity or those unable to handle the complexities of a multidose insulin regimen.
A basal-bolus strategy at mealtime should be used for patients not responding to such options, according to the writing group. Further, SGLT2, TZD or concentrated insulin could help during this stage of the disease, the researchers noted.
The updated position statement urges clinicians to consider complexity and cost involved with multiple combinations; the experts noted that complicated regimens could warrant HbA1c target reassessment or potential bariatric surgery in patients with obesity.
The updates remind the community that nutritional counseling and diabetes self-management education are integral parts of a therapeutic program.
“These will ensure that the patient has access to information on methods to reduce, where possible, the requirements for pharmacotherapy, as well as to safely monitor and control blood glucose levels,” the researchers wrote.
Latent autoimmune diabetes of adulthood (LADA) and the insulin requirements and metabolic changes in these patients should be concerns for clinicians, according to the writing group.
The various comorbidities potentially occurring in patients were emphasized in the revised statement, with new data on DPP-4 and SGLT2 inhibitors, as well as patient resources, among the areas clinicians want to consider.
“More long-term data regarding the cardiovascular impact of our glucose-lowering therapies will be available over the next 1 to 3 years,” the group wrote. “Information from these trials will further assist us in optimizing treatment strategies.”
The experts highlighted a comparative effectiveness study in the US to assess long-term outcomes of multiple agents used after metformin as a monotherapy, with results anticipated in 2020.
“The recommendations in this position statement will obviously need to be updated in future years in order to provide the best and most evidence-based recommendations for patients with type 2 diabetes,” the researchers wrote.
Disclosure: Please see study for full list of disclosures.
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