Liraglutide (Victoza – Novo Nordisk), a glucagon-like peptide-1 (GLP-1) receptor agonist given by subcutaneous injection, has been approved by the FDA for treatment of patients with type 2 diabetes. It can be used alone or in addition to oral antidiabetic drugs such as metformin (Glucophage, and others) or glimepiride (Amaryl, and others). Liraglutide is not recommended for first-line therapy and is not approved for use with insulin.

The cardiovascular safety of the thiazolidinedione rosiglitazone (Avandia – GlaxoSmithKline) is in the news again, with some authorities calling for its removal from the market (New York Times, February 19, 2010).

Saxagliptin (Onglyza - Bristol-Myers Squibb), the second oral dipeptidyl peptidase-4 (DPP-4) inhibitor to be marketed in the US, has been approved by the FDA for treatment of adults with type 2 diabetes.

Colesevelam (Welchol - Daiichi Sankyo - Med Lett Drugs Ther 2000; 42:102), a bile-acid sequestrant used to lower LDL cholesterol, has been approved by the FDA as an adjunct to diet and exercise in the treatment of type 2 diabetes. In unpublished studies summarized in the package insert, patients with type 2 diabetes taking metformin (Glucophage, and others), a sulfonylurea or insulin (each as either monotherapy or in combination with other anti-diabetic agents) were given colesevelam 3800 mg per day or placebo; colesevelam significantly reduced glycosylated hemoglobin (A1c) by about 0.5% more than placebo in all three trials. The mechanism is unclear.

Colesevelam can cause constipation, nausea and dyspepsia, increase serum triglyceride concentrations, and interfere with absorption of other oral drugs. One month's treatment with Welchol obtained from drugstore.com would cost about $200. Medical Letter consultants are not enthusiastic about prescribing it for this indication.

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Losing even a small amount of weight and increasing physical activity can prevent some of the complications of obesity, particularly type 2 diabetes. Diet and exercise are the preferred methods for losing weight but are associated with high long-term failure rates. Drugs may help some patients, but all currently available drugs for weight reduction have drawbacks. Gastric surgery can produce marked weight loss in the severely obese, but long-term data on safety are limited.

Avandaryl, a new fixed-dose tablet combining the thiazolidinedione rosiglitazone (Avandia) and the sulfonylurea glimepiride (Amaryl, and others), was recently approved by the FDA for treatment of type 2 diabetes. It is approved for patients already taking a combination of rosiglitazone and a sulfonylurea or those not adequately controlled on rosiglitazone or sulfonylurea monotherapy. Rosiglitazone is also available in a fixed-dose combination with metformin (Avandamet). Most patients with type 2 diabetes eventually require 2 drugs with different mechanisms to control hyperglycemia.

Exenatide injection (Byetta - Amylin/Lilly), a synthetic peptide that stimulates release of insulin from pancreatic beta cells, has been approved by the FDA as adjunctive therapy for patients with type 2 diabetes who have not achieved optimal glycemic control on metformin (Glucophage, and others), a sulfonylurea, such as glyburide (DiaBeta, and others), or both. Exenatide is not indicated for use with insulin.

Pioglitazone is the third thiazolidinedione ("glitazone") to be marketed in the USA for treatment of type 2 diabetes. Thiazolidinediones decrease resistance to insulin.