Juan P. Frias, MD
Clinical Assistant Professor of Medicine
University of California
San Diego, California
Chief Medical Officer
National Research Institute
Los Angeles, California
Can you provide some background, including dosing and units of each component, for the two fixed ratio, combination, insulin-plus-GLP-1 receptor agonist formulations that have been investigated and are likely to be approved?
From a front lines translational perspective, where are combination insulin-plus-GLP-1 RA regimens likely to fit into the sequencing algorithm for care of patients with T2D?
What markers and strategies do you recommend for titrating fixed-dose combination regimens? What dosing considerations apply to ensure optimal HA1c control?
Are there significant clinical differences—pharmacokinetic, safety, weight loss, control of PPG—between the two combination formulations, i.e. glargine insulin plus lixisenatide (iGlarLixi) vs. degludec insulin plus liraglutide (iDegLira)?
Given the established use of metformin and SGLT2 inhibitors as oral foundation agents, where do you believe the GLP-1 RA/insulin combination regimens, which are injectable, are likely to play the most important role in guideline-directed care?
How would deploy the fixed ratio combination agents in an obese patient who was not meeting HA1c target goals on metformin alone, or a second oral agent?
How would you deploy the fixed ratio combination regimens in patients who had documented postprandial hyperglycemia? Would one combination offer an advantage over the other, based on pharmacokinetic properties of the GLP-1 RA?
What is the appropriate way to add fixed ratio combination GLP-1 RA/insulin regimens to oral foundational therapy? Are these drugs added sequentially? Should the oral agents be discontinued?
What are the withdrawal and regimen adherence rates with the GLP-1 RA/insulin regimens, and how do the fixed ratio combination formulations affect GI side effects sometimes encountered with GLP-1 RAs? Is the incidence of side effects lower?
What was the physiological, safety, and compliance-focused rationale for combining basal insulin plus GLP-1 RA into a fixed ratio formulation? How would this approach achieve pan-glycemic (FBG and PPG) control?