Living guideline on drugs for type 2 diabetes: incorporating living evidence on benefits and harms, prognosis, and values and preferences

2024 Prague [Global Evidence Summit]

Agarwal A¹, Agoritsas T², Manja V³, Mustafa R⁴, Vandvik P⁵

¹MAGIC Evidence Ecosystem Foundation, Oslo, Norway; Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada

²MAGIC Evidence Ecosystem Foundation, Oslo, Norway; Division of General Internal Medicine, Department of Medicine, University Hospitals of Geneva, Geneva, Switzerland

³University of California Davis, Davis, California, United States

⁴Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada; Department of Internal Medicine, Division of Nephrology and Hypertension, University of Kansas, Kansas City, Missouri, United States

⁵MAGIC Evidence Ecosystem Foundation, Oslo, Norway; Department of Medicine, Innlandet Hospital Trust, Gjøvik, Norway

Background:

For patients with type 2 diabetes mellitus (T2DM), 2 drug classes—namely, sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists—demonstrate cardiorenal benefits, having resulted in a paradigmatic shift in management. This shift—with rapidly emerging evidence now also on weight loss—has introduced new challenges for evidence synthesizers and guideline developers. Beyond the need to dynamically update and compare the relative merits of 14 available drug classes across relevant outcomes, guidance must also account for variability in patient risk profiles and values and preferences.

Objectives:

To produce international living practice guidelines for T2DM drugs with a patient perspective, informed by living systematic reviews

Methods:

Since 2016, BMJ Rapid Recommendations, led by the MAGIC Evidence Ecosystem Foundation, has accelerated the translation of evidence into practice by developing trustworthy guidelines, applying current best standards and processes, methods (GRADE), and technology (MAGICapp).

Here, an international panel including patients, clinicians, and methodologists defined clinical questions in PICO format for drug alternatives in patients with T2DM. These informed systematic reviews on benefits and harms, prognosis, and values and preferences ultimately informed recommendations.

Results:

An updated network meta-analysis (NMA) of 816 trials (471,038 patients) confirmed moderate- to high-certainty evidence for cardiorenal benefits for SGLT-2 inhibitors and GLP-1 receptor agonists, with low-certainty evidence of important renoprotective effects with finerenone and weight loss effects with tirzepatide. The systematic review on prognosis (82 studies) did not identify credible risk prediction models for patients with established cardiovascular and renal disease, resulting in 3 pragmatically defined risk strata. The systematic review on patient values and preferences (30 studies, 12,062 patients) provided insufficient evidence to optimally inform what treatment options most patients would want. Taking all this evidence into account, the guideline panel issued risk-stratified recommendations for the 4 drug classes.

Conclusions:

This first iteration of an international living guideline for T2DM drugs emphasized the need for parallel living systematic reviews for treatment effects, prognosis, and values and preferences to inform risk-stratified, patient-centered recommendations and underscored the need for global collaboration as is being explored with the Alliance for Living Evidence (https://www.aliveevidence.org).