General Information

Symlin (pramlintide) is an antihyperglycemic agent. It is designed to mimic the activity of the naturally occurring hormone amylin, which is secreted together with insulin and is involved in post-prandial glucose control.

Symlin is specifically indicated for the mealtime treatment of type 1 and type 2 diabetes in combination with standard insulin therapy, in patients who have failed to achieve adequate glucose control on insulin monotherapy. It can be administered to type 2 diabetics also on metformin or sulfonylurea therapy.

Mechanism of Action

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Side Effects

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Dosing/Administration

Symlin is supplied as a clear sterile solution designed for subcutaneous injection. Recommended dosing varies depending on whether a patient has type 1or type 2 diabetes: for type 1 patients, initial recommended dosing is 15 mcg, which should be titrated at 15 mcg increments to a maintenance dose of 30 mcg or 60 mcg as tolerated. For type 2 patients, initial dose should be 60 mcg, with a single increment increase to 120 mcg as tolerated. NOTE: Initiation of Symlin therapy may require adjustments to insulin dosing schedules, and should be performed under the close supervision of a healthcare professional.

Clinical Trial Results

Approval of Symlin was supported by a number of clinical trials, investigating the drug in both type 1 and type 2 diabetic in both short- and long-term controlled trials, long term uncontrolled trials, and an open label study.

Type 1 diabetes
Symlin was evaluated for the treatment of type 1 diabetics (n=1717) in 3 long-term randomized, double-blind, placebo-controlled studies. Patients received 30 mcg or 60 mcg Symlin in addition to standard insulin therapy; in two of the trials, only minimal insulin dose adjustment was allowed, in order to isolate Symlin's efficacy; in the third, insulin dose was adjusted per standard medical practices. Symlin administration was seen to produce significant improvements in a number of measures at 6 months, including: change in HbA1c levels vs. baseline (-0.43 percent); placebo-subtracted HbA1c levels (-0.33 percent); change in total body weight (-1.1 kg); and placebo-subtracted total body weight (-1.7 kg).

The drug was also investigated for the treatment of type 1 diabetes in a dose titration study. This randomized, double-blind, placebo-controlled study enrolled patients with relatively good glycemic control (mean HbA1c = 8.1 percent). In addition to maintained standard insulin regimens, subjects received an initial dose of 15 mcg Symlin or placebo, which was titrated in 15 mcg intervals to 30 mcg or 60 mcg, based on whether subjects experienced significant nausea. Insulin dosing was reduced 30-50 percent during titration to reduce potential incidence of hypoglycemia. At six months, subjects receiving Symlin plus insulin achieved similar reductions in mean HbA1C levels, compared to subjects receiving placebo-plus-insulin (-0.47 +/- 0.07 percent versus -0.49 +/- 0.07 percent, respectively), while using a significantly lower total and fast-acting insulin dose (-11.7 percent, -22.8 percent from baseline). Symlin also produced weight loss relative to both baseline (-1.33) and placebo-plus-insulin (-2.6 kg)

Finally, Symlin was studied in the treatment of type 1 diabetes in an open-label clinical practice setting. Using a flexible dose regimen of insulin, the study enrolled type 1 diabetics unable to achieve glycemic control on insulin alone. The addition of Symlin to this regimen significantly reduced mean HbA1c levels (-0.18 percent) and body weight (-3.0 kg) at six months, and reduced total, short-acting, and long-acting insulin (-12.0 +/- 1.36, -21.7 +/- 2.81, and -0.4 +/- 1.59 percent, respectively), all relative to baseline.

Type 2 diabetes
Symlin was investigated for the treatment of type 2 diabetes in a pair of long-term randomized, double-blind, placebo-controlled studies. Patients received Symlin or placebo in addition to the patients existing regimens of fixed dose insulin with or without metformin and/or sulfonylurea. Symlin was found to produce significantly superior improvements in reduction in HbA1c levels (-.57 percent), placebo-subtracted HbA1c levels (-0.40 percent), body weight (-1.5 kg), placebo-subtracted body weight (-1.7 kg), percent change in rapid-acting insulin dose (-3.0 percent) and percent change in long-acting insulin dose (-0.2 percent), at 6 months.

Symlin was also investigated in an open-label clinical practice study in the treatment of type 2 diabetics whose disease was inadequately controlled by insulin therapy. The trial enrolled 166 patients, who received 120 mcg Symlin in addition to a standard flexible-dose insulin regimen. Results indicated that the drug produced reductions from baseline in mean HbA1c levels (-0.56 +/- 0.15 percent) and mean body weight (-2.76 +/- 0.34 kg). Symlin administration also reduced necessary doses of total, short-acting and long-acting insulin (-6.4 +/- 2.66 percent, -10.3 +/- 4.84 percent and -4.20 +/- 2.42 percent, respectively).