Type 2 Diabetes and Chronic Kidney Disease and Heart Failure

Describe your topic.: For adults with Type 2 diabetes (T2DM) with or without known chronic kidney disease who cannot attain adequate glucose control with metformin, what are the comparative risks and benefits of GLP-1 agonists and SGLT-2 inhibitors (as compared to placebo, DPP-4 inhibitors, basal insulin, thiazolidinediones, or sulfonylureas)? Important outcomes include acute renal failure, death due to renal causes, end-stage renal disease (or initiation of renal-replacement therapy), composite renal outcomes incorporating eGFR reduction and other outcomes specified above, and all-cause mortality. For adults with Type 2 diabetes (T2DM) and with or without known heart failure who cannot attain adequate glucose control with metformin, what are the comparative risks and benefits of GLP-1 agonists and SGLT-2 inhibitors (as compared to placebo, DPP-4 inhibitors, basal insulin, thiazolidinediones, or sulfonylureas)? Important outcomes include heart failure events, hospitalization for heart failure, and all-cause death.

Describe why this topic is important.: This topic is important because the recent 2018 Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) recommends SGLT-2 inhibitors specifically for adults with T2DM and chronic kidney disease (or T2DM and heart failure) who do not have adequate glucose control with metformin alone. These recommendations are based upon comparison of GLP-1 agonists and SGLT-2 inhibitors to placebo to evaluate impact on glycemic control. Meta-analyses of head-to-head trials comparing older to newer drugs for T2DM examine comparative effectiveness of the different drugs listed above for the outcome of cardiovascular death. The ADA Guidelines do not appear to consider evidence about the potential impact on renal and heart failure outcomes for these groups, however, and a patient-centered approach to care must consider all these relevant outcomes. We want to know more about the comparative effectiveness of these drugs for the renal and heart failure outcomes, if any evidence exists to inform this question.

Tell us why you are suggesting this topic.: We do not have the resources to conduct this systematic review ourselves, yet the standard of care is changing based on the American Diabetes Association Guidelines. GLP-1 agonists and SGLT-2 inhibitors are significantly more expensive than thiazolidinediones, basal insulin, and sulfonylureas; the cost effectiveness (i.e., how many renal events are being prevented, how many heart failure events are being prevented by substituting GLP-1 agonists and/or SGLT-2 inhibitors for the others) is unclear. As a large organization that absorbs the cost of both the drugs and the health outcomes, this question is relevant to our guideline and operational decisions.

Describe what you are doing currently and what you are hoping will change because of a new evidence report.: We are reviewing the primary studies comparing the newer drugs (GLP-1 agonists and SGLT-2 inhibitors) to placebo, focusing on the subgroups and outcomes relevant to chronic kidney disease and heart failure. However, we do not have the resources to find and do meta-analyses on older comparative studies evaluating GLP-1 agonists and SGLT-2 inhibitors vs. other drugs (with these outcomes). Our current recommendation does not specify that adults with chronic kidney disease or heart failure should preferentially receive GLP-1 agonists and/or SGLT-2 inhibitors, due to lack of certainty about whether the evidence supports these treatments based on the balance of benefits to harms. Subsequently, clinicians in our system may lack clarity on the best treatment approach, and undesirable variation in care may persistent. Our hope is that an Evidence Report would provide us with a more evidence-based understanding of the comparative risks and benefits, to inform this important part of our guideline.

How will you or your group use the information from a new evidence report?: We will directly apply the Evidence Report to inform our guideline update. We consistently look to Evidence Reports from the EPCs when developing Kaiser Permanente National Guidelines.

How would you or your group plan to disseminate information from the report? Who would you plan to disseminate it to?: Once we incorporate evidence from the report into our guideline, it is disseminated to the regions of our organization through our regional guideline directors. Guidelines are disseminated to clinicians, physician assistants, nurse practitioners, and other health care professionals in relevant specialty groups, as well as operations, clinical decision support developers, administrative and education staff, providers by email and newsletters, through regional physician portals, and by US mail for clinicians not connected to our email system (e.g., affiliate providers). Our guidelines are typically posted and featured on our national and regional intranet sites as well as an external website as appropriate.

Do you know of organizations that could use an evidence report to change clinical practice? Are you a part of, or have you been in contact with, any organizations that might implement the research findings of an evidence report?: Our organization could and would use an evidence report directly to change clinical practice standards for the Kaiser Permanente system, which comprises 12.8 million members. "Strong recommendations" within Kaiser Permanente translate across regions to clinical decision support in our electronic medical record and related local quality initiatives designed to carry out the recommendations.

Information About You: (optional)

If you are you making a suggestion on behalf of an organization, please state the name of the organization.: Kaiser Permanente

Please tell us how you heard about the Effective Health Care Program.: Through the use of the Evidence Reports from the EPCs for developing Kaiser Permanente National Guidelines

Effective Health Care Program