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● If the HbA1c value remains above the target longer than 3 months, you add an additional (i.e. second or third) hypoglycemic agent. The higher the HbA1c value, the more likely insulin (initially a long-acting one) will be required.
● Low costs and clinical data explain and justify the predominance of combinations involving metformin, sulfonylurea, and insulin. But uniform recommendations on combinations cannot be made due to paucity of long-term comparative-effectiveness trials. Rather, the combination suitable for a particular patient is the result of safety considerations, effectiveness, and tolerability. The latter two usually need to be established by trying different drugs.