Metformin is the first-line treatment for patients with diabetes because it reduces mortality rates. If metformin is contraindicated or is not tolerated, any one of the other available antihyperglycemic drugs may be used as monotherapy. These drugs are equally effective for glucose control, lowering A1c by approximately 1%. Evidence of their benefit for reducing mortality or morbidity, or improving health-related quality of life is lacking. A sulfonylurea, pioglitazone, or exenatide can be added to maximally dosed metformin if additional glycemic control is necessary. Sulfonylureas and pioglitazone often cause weight gain. The combination of metformin plus a sulfonylurea is associated with a greater risk of hypoglycemia and mortality than the combination of metformin and a thiazolidinedione (ie, glitazone). Thiazolidinediones are contraindicated in patients with severe heart failure or liver disease. Newer drug classes target incretin, the hormone that stimulates food-dependent insulin secretion. The incretin mimetic exenatide, a high-cost injectable drug, is similar to metformin for reduction of A1c and body mass index. Incretin-enhancing dipeptidyl-peptidase 4 inhibitors (ie, gliptins) are inferior to metformin for lowering A1c and body mass index; little is known about their effect on all-cause mortality. Fixed combination products might improve ease of use and adherence; they might also reduce cost and risk of adverse effects.
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