Peter Attia MD - The triple therapy: three free drugs that work better for diabetics | Dr. Ralph DeFronzo
The EDICT study challenges traditional diabetes treatment by using a triple therapy approach from the start, involving metformin, exenatide, and pioglitazone. This method addresses multiple pathophysiological issues simultaneously, unlike the conventional stepwise approach that often starts with metformin alone. The study followed 315 patients over six years, showing that 70% maintained an A1C level below 6.5%, compared to only 29% with the traditional ADA approach. This suggests that addressing multiple aspects of diabetes from the beginning can lead to better long-term control and fewer complications.
The study also highlights the cost-effectiveness of using older, cheaper drugs in combination, which can achieve significant improvements in insulin sensitivity and beta-cell function. Despite the potential for weight gain with pioglitazone, the benefits in terms of A1C reduction and overall diabetes management are substantial. The findings suggest a need for a paradigm shift in diabetes treatment, focusing on comprehensive, early intervention rather than a gradual escalation of therapy.
Key Points:
- Triple therapy from the start improves A1C control significantly better than traditional methods.
- 70% of patients in the EDICT study maintained A1C below 6.5% over six years.
- Older, cheaper drugs like metformin, exenatide, and pioglitazone are effective in combination.
- The approach addresses multiple diabetes-related issues simultaneously, improving insulin sensitivity and beta-cell function.
- The study suggests a shift towards early, comprehensive treatment rather than gradual escalation.
Details:
1. 🔬 EDICT Study: Transformative Diabetes Treatment
- The EDICT study implemented a triple therapy approach from the start, contrasting with the traditional method of sequential monotherapy for diabetes treatment.
- This approach utilized metformin, exenatide, and pioglitazone, each selected for their effectiveness in managing diabetes symptoms and progression.
- The study tracked 315 diabetic patients over six years, employing insulin and hypoglycemic clamps to monitor glucose levels and insulin sensitivity.
- Compared to the standard ADA approach—beginning with metformin, then adding sulfonylureas, and eventually insulin—the triple therapy aimed to maintain an A1C level of 6.5 or lower.
- Results showed a significant disparity after six years, with only 29% of patients on the traditional ADA regimen maintaining an A1C below 6.5, versus 70% on triple therapy.
- These findings suggest a potential shift in treatment protocols towards early intensive therapy to improve long-term outcomes for diabetics.
2. 📊 EDICT vs ADA: A Comparative Analysis
2.1. Insulin Sensitivity
2.2. Cost Analysis
3. 📜 Historical Insights: GRADE and Past Studies
- The speaker, a seasoned scientist and clinician with over 850 publications, has extensive experience with hundreds of thousands of patients, solidifying their credibility in clinical research.
- Utilizing insulin clamp studies, the speaker demonstrates significant improvements in insulin sensitivity and beta cell function with a sample of 315 people, indicating highly effective research tools.
- A therapy is highlighted that normalizes insulin sensitivity and beta cell function, achieving an A1C of less than 6.5 in 50% of patients, compared to a metformin and insulin regimen where 71% show no improvement.
- The GRADE study, backed by the National Institutes of Health, corroborates these findings as the third study to validate the therapy's effectiveness over traditional methods.
- The speaker's credentials and the study's findings are distinct yet complementary, reinforcing the study's credibility and impact.
4. 💊 Understanding Drug Mechanisms and Efficacy
- The 2020 study required participants to have failed on Metformin, highlighting the need to explore alternative treatments when initial therapies are ineffective.
- Sulfonylureas initially lower A1C levels but tend to lose effectiveness over time as they do not address the underlying cause of diabetes, leading to pancreatic burnout.
- DPP-4 inhibitors increase endogenous GLP-1 and GIP levels but are less potent compared to alternatives like semaglutide injections, resulting in limited long-term efficacy.
- While DPP-4 inhibitors provide an initial reduction in A1C, their diminishing impact over time highlights the necessity for more effective diabetes management solutions.
- The study emphasizes the importance of ongoing innovation in treatment options to overcome the limitations of current therapies and provide lasting effects.
5. 💰 Cost Dynamics in Diabetes Therapy
5.1. Therapy Effectiveness and Cost Comparison
5.2. Impact of Cost on Patient Choices
6. 🔍 Key Findings and Clinical Implications
- In patients with a starting A1C above 10, those on a mixed insulin regimen achieved an A1C of 7.1% after three years, but experienced hypoglycemia, whereas those on exenatide and pioglitazone reached an A1C of 6.1%.
- In a subgroup with starting A1C of 12.2, symptomatic patients treated with exenatide and pioglitazone reduced their A1C to 6.1% after three years, even without metformin.
- Utilizing exenatide and pioglitazone, two older and cost-effective medications, can significantly reduce A1C levels in severe type 2 diabetes cases, demonstrating their potential to reverse high-risk conditions.
- The study involved over 200 participants, indicating robust results due to sophisticated pathophysiologic measurements.
- A possible side effect is a slight weight gain; however, higher generation GLP-1 agonists can mitigate this, offering comprehensive benefits by reducing the cost factor.
7. 🎵 Musical Interlude
- No actionable insights can be extracted from this segment as it is a music interlude without spoken content.