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Several structural parameters differentiate these molecules that may explain the different clinical profiles ( Figure 3B )

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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

. () [2] Pi-Sunyer, X., et al