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In this “Ask Me Anything” (AMA) episode, Peter explores various pharmacologic tools commonly utilized to improve metabolic health and treat diabetes, including SGLT-2 inhibitors, metformin, and GLP-1 agonists. He examines the available data on these drugs, assessing their comparative effectiveness and their potential in the context of lifestyle interventions. Additionally, he offers insights into whether SGLT2 inhibitors hold promise as geroprotective agents beyond their effects on glycemic control. Next, Peter analyzes the relationship between statin usage and the risk of developing insulin resistance and type 2 diabetes, investigating possible causal pathways and providing insights into strategies for risk reduction. He offers insights on monitoring adverse statin effects and evaluating the need for adjustments, ultimately weighing the trade-off between the risk to overall metabolic health against the benefits of reducing apoB levels through statin use.

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We discuss:

• Pharmacologic tools for improving metabolic health, and the relationship between statins and insulin resistance [2:00];
• SGLT-2 inhibitors: how they work and help to manage type 2 diabetes [4:15];
• The history of SGLT2 inhibitors – from discovery to the current state [10:15];
• Comparing the various FDA-approved SGLT2 inhibitors [15:00];
• Other beneficial effects of SGLT2 inhibitors outside of glycemic control [20:15];
• Exploring SGLT2 inhibitors as potential geroprotective molecules [22:45];
• The side effects and risks associated with SGLT2 inhibitors [31:45];
• Medications, lifestyle interventions, and other considerations for treating diabetes and improving metabolic health [37:45];
• Metformin as a tool for pre-diabetics, and how metformin compares to lifestyle interventions [44:00];
• How GLP-1 agonists compare to metformin and SGLT2 inhibitors in terms of glycemic control and weight loss [49:15];
• Exploring the relationship between statin use and the risk of developing insulin resistance and type 2 diabetes [52:30];
• Possible mechanisms of statin-induced insulin resistance and diabetes, and potential mitigation strategies [1:04:30];
• How to monitor for adverse effects of statin use and assess the need for adjustments [1:11:45];
• Weighing the benefits and risks of statin use: does the diabetes risk outweigh the benefits of lowering apoB with a statin? [1:15:30];
• Parting thoughts [1:20:45]; and
• More.

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