General Information

Amaryl (glimepiride) is an insulin-sparing sulfonylurea agent.

Amaryl is specifically indicated as a first-line therapy to lower blood glucose in people with type II diabetes whose high blood glucose cannot be controlled by diet and exercise alone.

Amaryl is supplied as a tablet for oral administration. Amaryl should be administered with breakfast or the first main meal of the day. The recommended starting dose of Amaryl is 1 mg or 2 mg once daily. Patients at increased risk for hypoglycemia (e.g., the elderly or patients with renal impairment) should be started on 1 mg once daily. After reaching a daily dose of 2 mg, further dose increases can be made in increments of 1 mg or 2 mg based upon the patient’s glycemic response. Uptitration should not occur more frequently than every 1 to 2 weeks. A conservative titration scheme is recommended for patients at increased risk for hypoglycemia. The maximum recommended dose is 8 mg once daily.

Clinical Trials

The FDA approval of Amaryl was based on a 14-week, multicenter, randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of Amaryl monotherapy. A total of 304 patients with type 2 diabetes already treated with sulfonylurea therapy were enrolled in the trial. Patients discontinued their sulfonylurea therapy then entered a 3-week placebo washout period followed by randomization into 1 of 4 treatment groups: placebo (n=74), Amaryl 1 mg (n=78), Amaryl 4 mg (n=76), and Amaryl 8 mg (n=76). All patients randomized to Amaryl started 1 mg daily. Patients randomized to Amaryl 4 mg or 8 mg had blinded, forced titration of the Amaryl dose at weekly intervals, first to 4 mg and then to 8 mg, as long as the dose was tolerated, until the randomized dose was reached. Patients randomized to the 4 mg dose reached the assigned dose at Week 2. Patients randomized to the 8 mg dose reached the assigned dose at Week 3. Once the randomized dose level was reached, patients were to be maintained at that dose until Week 14. Compared to placebo, treatment with Amaryl 1 mg, 4 mg, and 8 mg daily provided statistically significant improvements in HbA1c compared to placebo.

Mechanism of Action

Amaryl (glimepiride) primarily lowers blood glucose by stimulating the release of insulin from pancreatic beta cells. Sulfonylureas bind to the sulfonylurea receptor in the pancreatic beta-cell plasma membrane, leading to closure of the ATP-sensitive potassium channel, thereby stimulating the release of insulin.