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The iQ&A Interactive Medical Intelligence Zone for Glycemic Regulation
The iQ&A Interactive Medical Intelligence Zone for Glycemic Regulation
Why do clinicians managing patients with T2D need to be aware of the trials, physiologic basis, side effects and other dimensions of deploying fixed ratio, long-acting insulin-GLP-1 RA combination regimens?
Are there significant clinical differences—pharmacokinetic, safety, degree of weight loss, control of PPG—between the two combination formulations, i.e. glargine insulin plus lixisenatide (iGlarLixi) vs. degludec insulin plus liraglutide (iDegLira)?
From a translational perspective, who are the ideal patient candidates for the fixed ratio, combination formulations, i.e. glargine insulin plus lixisenatide (iGlarLixi) vs. degludec insulin plus liraglutide (iDegLira)?
What insights have we gained about drug-based management of the diabetic heart?
What insights have we gained about drug-based management of the diabetic heart?
What is your current perspective on the LEADER Trial and how should we translate its findings to the front lines of diabetes care? Can you describe the trial design?
How do slow dose titration strategies for the fixed ratio, combination formulations, i.e. glargine insulin plus lixisenatide (iGlarLixi) vs. degludec insulin plus liraglutide (iDegLira) potentially affect the side effects seen?
From practical perspective, where are combination insulin-plus-GLP-1 RA regimens likely to fit into the sequencing algorithm for care of patients with T2D?
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?
How were the trials designed that evaluated the effectiveness and safety of the fixed ratio combination of insulin glargine and lixisenatide, and what did we learn about titration strategies and mitigating side effects of each components?
Which patients with T2D will be the most appropriate candidates for the fixed ratio, combination regimens, i.e., iGlarLixi or iDegLira? And just how effective, tolerable, and safe are these formulations at lowering HA1c levels?
Can you provide some discrete clinical and patient profiles where fixed ratio, combination regimens consisting of a long-acting insulin and GLP-1 RA should be strongly considered?
Why are the risks of hypoglycemia very low when using the fixed ratio, combination regimens? Does this have to do with slow titration or mechanistic complementarity? By what mechanism do they mitigate hypoglycemic risk?
Are there clinically relevant differences between the fixed ratio, combination regimens— iGlarLixi or iDegLira— consisting of a long-acting insulin and GLP-1 RA?
From a practical, clinical perspective what advantages are offered by the two fixed ratio combination formulations, i.e. glargine insulin plus lixisenatide vs. degludec insulin plus liraglutide that seem to be on their way to approval?
How do the PK/PD dimensions of GLP-1-RAs determine their proper alignment with specific glycemic regulation needs (FPG vs PPG) and with specific clinical profiles of patients with T2D?
What have your studies shown as far as the optimal way to advance basal insulin therapy, and combining basal insulin with either prandial insulin or a GLP-1 RA?
What do we know about the relationship between PPG and cardiovascular risk?
What do we know about the relationship between PPG and cardiovascular risk?
What specific strategies are currently in the T2D pharmacologic toolkit that have been shown effective for reducing PPG? Where do GLP-1 RAs fit into this scheme?
Are there head-to-head comparisons looking at the effects of different GLP-1 RAs on PPG control? What are the results and implications of those studies?
How do we define PPG? How do we confirm its presence as an actionable metabolic derangement in need of intervention? And where does iGlarLixi fit into this treatment algorithm for PPG?
What attributes—mechanistically, metabolically, and physiologically—of GLP-1 RAs, in your mind, support their position as foundational agents across a broad spectrum of patients with T2D?
Within the class of GLP-1 RAs, are there important comparative distinctions—dosing, PK/PD, side effects, weight loss, lipid profiles, and BP—that have clinical relevance that you believe should be highlighted? How do they differentially affect PPG?
What is the rationale of combining GLP-1 RAs and long-acting insulin into fixed ratio combination agents?
What critical advances in the development of long-acting insulin and GLP-1 RA—and combination approaches using both—are having a positive impact on management of T2D? How should PK/PD properties affect our choice of specific GLP-1 RA? ...
What are the ideal clinical profiles for and distinctions among the fixed ratio, combination formulations? What are their potential advantages—i.e., reduced risk of weight gain and hypoglycemia —and unique therapeutic windows of opportunities?
How will fixed ratio, basal insulin-GLP-1 RA combinations likely fit into the sequencing algorithm for diabetes care? How do we select among the available options? And in whom should we use these formulations?
Why, in both ADA and AACE guidelines statements, do GLP-1 receptor agonists represent a foundational approach for management of T2D?
In what setting and in what patient profiles do GLP-1 RAs make most sense? What degrees of HA1c reduction are seen?
What is the rationale, therefore, of combining GLP-1 RAs and basal insulin into fixed ratio combination agents?
Can you provide clinical profiles where there is a strong rationale to move from a regimen consisting of metformin and SGLT2 inhibitor, to a fixed ratio combination of a basal insulin plus GLP-1 RA?
What is the importance of postprandial hyperglycemia (PPG) and glucose excursions as a management metric and what are the implications for selecting GLP-1 RAs?
What is the physiologic rationale of combining GLP-1 RAs and basal insulin into fixed ratio combination agents such as iGlarLixi and iDegLira?
What is the role of PPG as a determinant of achieving comprehensive HA1c level control? And how early in the course of T2D management do you think fixed ratio, combination basal insulin-GLP-1 RA formulations play a role?
What are the still unanswered questions about combination basal insulin-GLP-1 RA formulations?
What are the still unanswered questions about combination basal insulin-GLP-1 RA formulations?
What is your interpretation of the results from the studies evaluating the effectiveness and safety of fixed ratio insulin-GLP-1 RA combinations?
For what reasons does insulin remain a foundational therapy for managing patients with T2D? And why does the addition of a GLP-1 RA potentially augment the utility of insulin-based management?
What is the physiological, safety, efficacy and compliance-focused rationale for combining basal insulin plus GLP-1 RA into a fixed ratio formulation? And how does this strategy impact pan-glycemic—FPG and PPG—control?
Can you identify the specific composition of fixed ratio combination long-acting insulin/GLPA-1 RA formulations, and how clinicians should titrate and deploy these agents?
How would approach a mildly obese patient with T2D on a maximum dose of metformin who is not yet achieving FPG or PPG target goals?
How would you approach a 65-year old patient with T2D who has reasonable control of FBG but clear documentation of PPG?
What level of HA1c reduction is achieved with the fixed ratio combination and how is the side effect profile of the GLP-1 RA affected by the combination formulation and the titration strategy it utilizes?
From a practical, titration perspective what important clinical guidance can you provide to optimize effectiveness of the fixed ratio insulin-GLP-1 RA combination?
Where might the fixed ratio, combination regimens consisting of a long-acting insulin and GLP-1 RA fit into the ADA and AACE guidelines and how do your see their use in the sequencing algorithm for T2D?
How would deploy the fixed ratio combination agents in a 58-year old obese male patient who was not meeting HA1c target goals on metformin alone, or a second oral agent?
What is the importance of postprandial hyperglycemia (PPG) and glucose excursions as a management metric and what are the implications for selecting a specific GLP-1 RA with a specific PK/PD profile?
From a practical perspective, how do we assess to what degree PPG is playing a role in failing to achieve goal-directed HA1c levels? How do we use FPG and PPG levels to determine the need for agents useful for PPG control?
What was the physiological, safety, and compliance-focused rationale for combining basal insulin plus GLP-1 RA into a fixed ratio formulation?
How important is the mechanistic complementarity between basal insulin and GLP-1 RAs and what implication does this have for the safety and efficacy of fixed ratio combinations such as iGlarLixi and iDegLira?
What should we expect as far as weight gain, risk of hypoglycemia, and degree of HA1c lowering with fixed ratio combinations such a iGlarLixi and iDegLira?
What is meant exactly by a “fixed ratio” combination?
Can we extrapolate from what we learned about liraglutide in the LEADER trial to combination therapy that would employ a basal insulin in combination with this GLP-1 RA?
Does the LEADER trial data provide any guidance for how we might use fixed ratio combinations of basal insulin plus GLP-1 RA, or should we avoid such cross-trial comparisons?
What is the underlying physiology that explains the role of incretins in the disease processes leading to T2D?
What incretin-targeted therapies are available to modulate the incretin hormones and what are the clinical differences among the available options?
What is the rationale for combining basal insulin plus GLP-1 RA into a fixed ratio formulation? How does this strategy impact pan-glycemic—FPG and PPG—control and other metabolic target goals and risk factors?
Why is the combination of basal insulin and a GLP-1 RA logical from the standpoint of mechanistic complementarity?
From a clinical perspective, who are the ideal patient candidates for the fixed ratio, combination formulations, i.e. glargine insulin plus lixisenatide vs. degludec insulin plus liraglutide?
How would specific basal insulin-GLP-1 RA combination agents be used in specific patient populations with T2D? Are there trials that shed light on this?
What are the important developments at ADA 2016 as far as GLP-1 RAs?
What are the important developments at ADA 2016 as far as GLP-1 RAs?
How do make sense of the results and designs of the various cardiovascular outcome trials, including the LEADER trial, in patients with T2D and what do you believe is the take home message?
Can you review for us the design and rationale of the LEADER trial?
Can you review for us the design and rationale of the LEADER trial?
What are the translational implications of the LEADER trial based on the results reported at ADA 2016?
What do we know about dosing as it might impact CV outcomes, for liraglutide in the LEADER Trial, and how does this compare to what we learned from SGLT2 inhibitor-based CV outcomes trials?
What are the physiologic properties of incretin system-targeting agents?
What are the physiologic properties of incretin system-targeting agents?
What are the PK/PD properties for GLP-1 RAs and how do these differences affect their clinical roles? And specifically, how do long- vs. short-acting GLP-1 RAs affect PPG vs FPG?
Based on physiologic properties, which patients are eligible for short- vs long-acting GLP-1 RAs? And why is the combination of basal insulin and GLP-1 RA a reasonable strategy?
What are the physiologic and clinical properties of incretin system-targeting agents?
What are the physiologic and clinical properties of incretin system-targeting agents?
What are the multi-factorial effects of GLP-1 RAs?
What is the physiologic and clinical rationale for combining basal insulin and a GLP-1 RA as a treatment strategy for T2D?
What is the mechanism by which GLP-1 RAs induce weight loss?
What is the mechanism by which GLP-1 RAs induce weight loss?
At what point in the ADA and AACE sequencing algorithm for glycemic control in patients with T2D is the use of GLP-1 RA recommended? What are the treatment triggers for GLP-1 RA?
What degree of HA1c lowering do the studies report with the use of GLP-1 RAs?
What degree of HA1c lowering do the studies report with the use of GLP-1 RAs?
What degree of HA1c lowering are studies reporting with fixed ratio combinations using a basal insulin plus GLP-1 RA?
What aspects of GLP-1 RA do you think are most important for the practicing physician caring for patients with T2D?
How do you think you will use the combination formulations in real practice? How will you titrate these agents?
What degree of HA1c reductions can we expect to see with fixed ratio, basal insulin-GLP-1 RA combinations?
Why Is it important to look for and treat PPG?
What is the role of incretin axis for lowering PPG?
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?
From an HA1c control perspective, what is the advantage of using GLP-1 RAs in combination with long-acting insulin rather than as stand-alone therapy or as add-on to metformin?
Who do you believe would benefit from a fixed ratio combination of a GLP-1 RA with long-acting insulin?
What are the cardiovascular effects of GLP-1 RAs?