• If no contraindications are present always start with metformin as initial therapy in most patients with type 2 diabetes. However, consider insulin as first–line drug in patients presenting with A1c >10%, fasting sugar >250 mg/dL, random sugar consistently >300 mg/dL, or ketonuria.
  • Start with metformin at the time of diabetes diagnosis, along with lifestyle interventions. Titrate dose to its maximally effective dose (2000–2500 mg/day) over 1 to 2 months.
  • If situations predisposing to lactic acidosis are present, avoid metformin and consider a shorter–duration sulfonylurea.
  • Star with lifestyle intervention first, at the time of diagnosis. If lifestyle interventions have not produced a significant reduction in symptoms of hyperglycemia or in sugar levels after 1 or 2 weeks, add the first drug.
  • Those who cannot be given metformin or sulfonylureas, repaglinide is an alternative, particularly in a patient with chronic kidney disease at risk for hypoglycemia.
  • Other alternative is a pioglitazone, which may be considered in patients with lower initial A1c values or if there are specific contraindications to sulfonylureas. There is a concern about atherogenic lipid profiles and a potential increased risk for cardiovascular events with rosiglitazone.
  • One can consider sitagliptin as monotherapy for those intolerant of or have contraindications to metformin, sulfonylureas, or thiazolidinediones. It is a drug of choice as initial therapy in a patient with chronic kidney disease at risk for hypoglycemia. It is however, less potent than repaglinide, which can also be used safely in patients with chronic kidney disease.
  • In patients in whom it is difficult to distinguish type 1 from type 2 diabetes, start with insulin.
  • Further adjustments of therapy should be made every three months based on the A1C result aiming it close to the non diabetic range. If A1c values >7%, one need to further adjust the diabetic regimen.
  • If A1c remains >7% another drug should be added within 2 to 3 months of initiation of the lifestyle intervention and metformin.
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