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Here are the key recommendations: 1 Type 2 Diabetes with No Relevant Comorbidities First-line therapy: Modified-release Metformin + SGLT2 inhibitor If Metformin is contraindicated or not tolerated: SGLT2 inhibitor monotherapy 2 Type 2 Diabetes with Heart Failure Initial therapy: Modified-release Metformin + SGLT2 inhibitor If Metformin cannot be used: SGLT2 inhibitor alone 3 Type 2 Diabetes with Atherosclerotic Cardiovascular Disease (ASCVD) Recommended combination therapy: Metformin SGLT2 inhibitor Semaglutide (up to 1 mg weekly) If Metformin is contraindicated: SGLT2 inhibitor + Semaglutide 4 Early-Onset Type 2 Diabetes Initial treatment: Modified-release Metformin + SGLT2 inhibitor Consider adding: GLP-1 receptor agonist or Tirzepatide for improved glycemic and cardiometabolic outcomes 5 Type 2 Diabetes with Obesity Recommended first-line therapy: Modified-release Metformin + SGLT2 inhibitor Additional weight-focused therapies may be considered based on individual patient needs

The FDA continues to monitor GLP-1 receptor agonists for psychiatric effects, and any emergence of suicidal ideation during treatment should be taken seriously

Moreover, insulin resistance of the adipose tissue, associated with overweight/obesity, contributes to the flux of FFA from adipose tissue to the liver through unrestricted lipolysis (19)

Once this critical transport mechanism is restored, the mitochondria can resume beta-oxidation, converting those dormant, accumulated fats into a steady, reliable stream of ATP