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Methandien>1 indicates increased risk; OR 10,000 participants over 1–2 years; no significant increase in overall adverse events compared to placebo. | Routine use is safe for most patients after screening. |
| **Cardiovascular** | No increased risk of major adverse cardiovascular events (MACE). Some evidence of reduced all‑cause mortality with sitagliptin when combined with metformin. | Safe in patients with established CVD; may provide modest benefit. |
| **Renal** | No significant renal toxicity noted. However, sitagliptin is cleared renally; dose adjustment required if eGFR

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