2020 糖尿病血糖控制 6 第二型DM的初始治療

Initial Therapy
Metformin should be started at the time type 2 diabetes is diagnosed unless there are contraindications; for many patients this will be monotherapy in combination with lifestyle modifications. Metformin is effective and safe, is inexpensive, and may reduce risk of cardiovascular events and death (35). Metformin is available in an immediate-release form for twice-daily dosing or as an extended-release form that can be given once daily. Compared with sulfonylureas, metformin as first-line therapy has beneficial effects on A1C, weight, and cardiovascular mortality (36); there is little systematic data available for other oral agents as initial therapy of type 2 diabetes. The principal side effects of metformin are gastrointestinal intolerance due to bloating, abdominal discomfort, and diarrhea; these can be mitigated by gradual dose titration. The drug is cleared by renal filtration, and very high circulating levels (e.g., as a result of overdose or acute renal failure) have been associated with lactic acidosis. However, the occurrence of this complication is now known to be very rare, and metformin may be safely used in patients with reduced estimated glomerular filtration rates (eGFR); the FDA has revised the label for metformin to reflect its safety in patients with eGFR ≥30 mL/min/1.73 m2 (37). A recent randomized trial confirmed previous observations that metformin use is associated with vitamin B12 deficiency and worsening of symptoms of neuropathy (38). This is compatible with a recent report from the Diabetes Prevention Program Outcomes Study (DPPOS) suggesting periodic testing of vitamin B12 (39).

In patients with contraindications or intolerance to metformin, initial therapy should be based on patient factors; consider a drug from another class depicted in Fig. 9.1. When A1C is ≥1.5% (12.5 mmol/mol) above the glycemic target (see Section 6 “Glycemic Targets,” https://doi.org/10.2337/dc20-S006, for selecting appropriate targets), many patients will require dual combination therapy to achieve their target A1C level (40). Insulin has the advantage of being effective where other agents are not and should be considered as part of any combination regimen when hyperglycemia is severe, especially if catabolic features (weight loss, hypertriglyceridemia, ketosis) are present. It is common practice to initiate insulin therapy for patients who present with blood glucose levels ≥300 mg/dL (16.7 mmol/L) or A1C >10% (86 mmol/mol) or if the patient has symptoms of hyperglycemia (i.e., polyuria or polydipsia) or evidence of catabolism (weight loss) (Fig. 9.2). As glucose toxicity resolves, simplifying the regimen and/or changing to oral agents is often possible. However, there is evidence that patients with uncontrolled hyperglycemia associated with type 2 diabetes can also be effectively treated with a sulfonylurea (41).