Approximately 40% of all type 2 diabetics take a drug from the sulfonylurea class (see TABLE 2) — usually glyburide, glipizide, or chlorpropamide. The sulfonylureas cause the beta-cells of the pancreas to increase insulin secretion. Weight gain is common with sulfonylurea use and ranges from 1.8 to 2.8 kg.
|
Table 2. Antidiabetic Drugs Used to Treat Type 2 Diabetes |
|||
| Drug | Mechanism of Action | Effect on Weight During Initiation of Therapy up to One Year | Potential Side Effects |
| Sulfonylureas | Increased insulin secretion by pancreatic beta cells | 1.8 to 2.8 kg weight gain | Weight gain, hypoglycemia |
| Metformin | Decreased hepatic glucose production/enhanced glucosedisposal by skeletal muscle | 0.6 to 0.8 kg weight reduction | Abdominal bloating, nausea, cramping, diarrhea |
| Acarbose | Inhibits alpha-glucosidase and alpha-amylase | None or negligible | Flatulence, diarrhea, abdominal discomfort |
| Troglitazone | Increased glucose disposal in muscle tissue/decreased hepatic glucose production | None to 0.6 kg weight gain | Few reported (jaundice due to idiosyncratic drug reaction) |
| Insulin | Normal physiologic effects | Up to 6.0 kg weight gain | Hypoglycemia |
Metformin (Glucophage) is a biguanide antidiabetic agent that reduces basal hepatic glucose production by altering gluconeogenesis and/or glycogenolysis. Additionally, metformin decreases insulin resistance by promoting insulin-sensitive glucose uptake by muscle cells. Metformin can also reduce triglycerides and low-density lipoprotein (LDL) cholesterol, and increase high-density lipoprotein (HDL) cholesterol. Weight reductions of 0.6 to 0.8 kg have been noted in study subjects taking metformin.When metformin is combined with the sulfonylurea glyburide, however, average weight gains of 0.7 kg have been reported.
Acarbose (Precose) is an alpha-glucosidase inhibitor as well as an inhibitor of pancreatic alpha-amylase. These enzymes are responsible for the hydrolysis of oligosaccharides and related saccharides in the small intestine. Inhibition of these enzymes results in reductions in the rate and extent of carbohydrate digestion and absorption of glucose in the body. Patients treated with acarbose tend to experience no changes in weight or serum lipids.
Troglitazone (Rezulin) belongs to a new class of drugs called thiazolidinediones. It works by decreasing insulin resistance. Its primary actions involve increasing glucose disposal from the blood stream into muscle tissue and decreasing glucose production in the liver. No or very small weight changes in patients taking troglitazone are seen. Decreases in plasma triglyceride and free fatty acid levels have also been reported.
Approximately three-quarters of all the insulin used in the U.S. is taken by people with type 2 diabetes. Exogenous insulin reduces hepatic glucose production in type 2 diabetics. It also increases insulin-stimulated glucose utilization and endogenous insulin secretion. Weight gain is common in patients using insulin and may include gains up to 6.0 kg in a 12-month period.