the health strategist
institute for
strategic health transformation
Joaquim Cardoso MSc.
Chief Research & Strategy Officer (CRSO),
Chief Editor and Senior Advisor
August 28, 2023
What is the message?
While metformin has traditionally been the preferred first-line treatment for type 2 diabetes (T2D) due to its safety and affordability, the emergence of newer glucose-lowering agents with cardiovascular and renal benefits has led to a shift in treatment paradigms.
- Recent evidence from cardiovascular outcome trials (CVOTs) indicates that GLP-1 receptor agonists and SGLT2 inhibitors provide cardiorenal protection in addition to glycemic control.
- As a result, current guidelines recommend considering these agents as first-line options for T2D patients with or at high risk of cardiovascular disease, heart failure, or chronic kidney disease.
It is of high importance the individualization of treatment based on patient characteristics, preferences, and access to medications to achieve optimal outcomes in managing T2D and its associated complications.
One page summary
Metformin, initially approved by the FDA in 1994, has been the preferred first-line treatment for type 2 diabetes (T2D) due to its effectiveness, safety, and affordability.
However, the emergence of newer glucose-lowering agents with cardiovascular and renal benefits has raised questions about metformin’s continued role. Recent evidence from cardiovascular outcome trials (CVOTs) and guideline recommendations highlight the evolving landscape of T2D treatment.
Cardiovascular Outcome Trials Transform Standard of Care: In 2008, the FDA mandated CV risk evaluation for T2D therapies.
CVOTs for dipeptidyl peptidase-4 (DPP-4) inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors established their cardiovascular safety and even demonstrated reduced major adverse cardiovascular events (MACE) relative to placebo. Trials like LEADER and EMPA-REG OUTCOME revealed cardioprotective benefits of GLP-1 receptor agonists and SGLT2 inhibitors, shifting guidelines towards holistic management.
Individualizing Care to Attain Cardiorenal-Metabolic Goals: CVOTs assessed GLP-1 receptor agonists and SGLT2 inhibitors alongside metformin, but evidence supports their benefits regardless of metformin use.
Dedicated SGLT2 inhibitor renal outcome trials (CREDENCE, DAPA-CKD, EMPA-KIDNEY) confirmed renal and cardiovascular benefits. GLP-1 receptor agonists and SGLT2 inhibitors were endorsed for ASCVD, heart failure (HF), and chronic kidney disease (CKD) in updated ADA and AACE guidelines, regardless of glycemic control needs.
Optimizing Guideline-Directed Medical Therapy: Challenges to optimal therapy include underutilization in high-risk subgroups due to cost, access, and clinician barriers.
While metformin remains important, GLP-1 receptor agonists and SGLT2 inhibitors are viable first-line options for T2D patients at risk of cardiovascular and renal complications.
Conclusion:
The role of metformin in first-line T2D therapy depends on individual patient characteristics. Metformin remains vital in combination with lifestyle changes for patients without key cardiorenal comorbidities.
However, evidence supports considering GLP-1 receptor agonists and SGLT2 inhibitors as first-line options for patients with or at high risk for ASCVD, HF, or CKD, irrespective of background metformin use.
Treatment choices should be tailored to patient goals, preferences, and access to medication.
Efforts to enhance patient access to newer therapies are crucial for optimal outcomes.
This is a summary of the article “First-Line Therapy in T2D: Has Metformin Been ‘Dethroned’?”, written by Joshua J. Neumiller, PharmD, CDCES; Radica Z. Alicic, MD, MSc, and published on August 15, 2023 at Medscape.
