Fixed-ratio basal insulin/ glucagon-like peptide 1 (GLP-1) agonist combinations appear to be a better option than sequential intensification for patients with type 2 diabetes who remain uncontrolled on oral antidiabetic drugs, according to ADA Past President Vivian Fonseca, MD.
Dr. Fonseca was one of four speakers in the Sunday morning symposium Prioritizing Injectable Therapies in Type 2 Diabetes. He said that he would like to see the Food and Drug Administration approve fixed-ratio combinations (FRC) as a primary indication for type 2 diabetes patients. The FDA has approved two FRCs, insulin degludec/liraglutide and insulin glargine/lixisenatide, but only for patients inadequately controlled on basal insulin or a GLP-1 receptor agonist.
“That is a limitation that I hope will change. There are studies that are ongoing to provide more data to submit to the FDA to get this label change,” said Dr. Fonseca, Assistant Dean for Clinical Research, Chief of the Section of Endocrinology, and Professor of Medicine at Tulane University.
Both FRCs show no differences in glycemic control or adverse affects, Dr. Fonseca said. And both show better efficacy than a component given alone, with improved fasting plasma glucose and postprandal glucose levels, lower rates of hypoglycemia and weight gain versus insulin monotherapy, slower titration that reduces gastrointestinal side effects, and a simplified regiment.
Liraglutide is also indicated for preventing cardiovascular (CV) events.
“You have a single injection that addresses multiple defects with the least number of injections, which may improve patient adherence,” Dr. Fonseca said.
Juan P. Frías, MD, President and Principal Investigator at the National Research Institute, is a proponent of GLP-1 receptor agonists over basal insulin as long as no contraindications or safety concerns exist. Based on head-to-head random clinical trials and real-world analyses, Dr. Frías said GLP-1 receptor agonists offer improved or similar A1C reduction, a more favorable body weight profile, lower risk of non-severe hypoglycemia, and a more favorable CV risk profile than basal insulin.
GLP-1 receptor agonists do, however, have higher gastrointestinal-related side effects. And basal insulin should be used first if the patient has signs of significant insulin insufficiency, he said.
“Almost all patients will need intensification and should eventually be on both agents,” Dr. Frías said.
Also during the session, Helena W. Rodbard, MD, Medical Director at Endocrine and Metabolic Consultants, presented a lecture titled “Therapy Progression After Basal Insulin—GLP-1 Agonist versus Prandial Insulin versus Premixed Insulin.”
In the FullSTEP study (Treatment Intensification with Stepwise Addition of Prandial Insulin Aspart Boluses Compared with Full Basal-bolus Therapy), researchers found that progressive intensification of prandial insulin therapy—starting at one injection a day and increasing depending on A1C levels—provided a significantly lower risk of hypoglycemia with glycemic control compared to thrice-daily basal-bolus injections. The stepwise arm of the study had a lower total daily insulin dose and fewer injections a day.
Juris Meier, MD, Chief Physician in the Department of Diabetology and Gastrointestinal Endocrinology at St. Josef Hospital, Ruhr University Bochum, Germany, examined how differences in GLP-1 analogs impact treatment. Liraglutide, dulaglutide, and semaglutide have an advantage in A1C reduction, he said. For weight loss, liraglutide and semaglutide are good choices, while dulaglutide and semaglutide are top choices for convenience and adherence, and semaglutide and liraglutide have better CV outcomes.
Exanatide-LAR is also good for CV outcomes and mitigating gastrointestinal side effects, Dr. Meier said, while exenatide and lixisenatide help with reducing postprandal glucose heart rate.