Pramlintide is a synthetic analog of islet amyloid polypeptide (IAPP or amylin). When given subcutaneously, it delays gastric emptying, suppresses glucagon secretion, and decreases appetite. It is approved for use both in type 1 diabetes and in insulin-treated type 2 diabetes. In 6-month clinical studies with type 1 and insulin-treated type 2 patients, those on the drug had an approximately 0.4% reduction in HbA1c and about 1.7 kg weight loss compared with placebo. The HbA1c reduction was sustained for 2 years but some of the weight was regained. The drug is given by injection immediately before the meal. Hypoglycemia can occur, and it is recommended that the short-acting or premixed insulin doses be reduced by 50% when the drug is started. Nausea was the other main side effect, affecting 30-50% of persons but tended to improve with time. In patients with type 1 diabetes, the initial dose of pramlintide is 15 mcg before each meal and titrated up by 15 mcg increments to a maintenance dose of 30 mcg or 60 mcg before each meal. In patients with type 2 diabetes, the starting dose is 60 mcg premeals increased to 120 mcg in 3 to 7 days if no significant nausea occurs.
6. Drug combinations
Several drug combinations are available in different dose sizes, including glyburide and metformin (Glucovance); glipizide and metformin (Metaglip); rosiglitazone and metformin (Avandamet); pioglitazone and metformin (ACTOplus Met); and rosiglitazone and glimepiride (Avandaryl). These drug combinations, however, limit the clinician’s ability to optimally adjust dosage of the individual drugs and for that reason are not recommended.
7. Safety of the antihyperglycemic agents
The UKPDS has put to rest previous concerns regarding the safety of sulfonylureas. It did not confirm any cardiovascular hazard among over 1500 patients treated intensively with sulfonylureas for over 10 years, compared with a comparable number who received either insulin or diet therapy. Analysis of a subgroup of obese patients receiving metformin also showed no hazard and even a slight reduction in cardiovascular deaths compared with conventional therapy.
The currently available thiazolidinediones have not to date exhibited the idiosyncratic hepatotoxicity seen with troglitazone. However, these drugs can precipitate congestive heart failure and should not be used in patients with New York Heart Association class III and IV cardiac status. Lactic acidosis from metformin is quite rare and probably not a major problem with its use in the absence of major risk factors such as impaired renal or hepatic disease or conditions predisposing to hypoxia.