In 2005 pramlintide was approved for use in type 1 diabetes. This agent is an analogue of the hormone amylin, a peptide normally co-secreted with insulin. The primary function of amylin is to reduce postprandial hyperglycemia and this is accomplished by three mechanisms: a reduction of mealtime glucagon secretion, a delay of gastric emptying, and a primary effect to reduce satiety. This latter effect is likely related to the fact that amylin receptors have been found in the brain, thus also classifying the peptide as a “neurohormone”. Although the pharmacokinetics and pharmacodynamics of pramlintide are similar to human amylin (the half-life is about 48 minutes with an effect on blood glucose lasting about 3 hours), pramlintide the analogue does not aggregate, form insoluble particles, or adhere to surfaces, as does preparations of amylin itself. Mean A1c reductions of about 0.5-0.7% have been noted in clinical trials.

Pramlintide is injected just prior to meals at an initial dose of 15 mcg per meal and increased as tolerated every three days to a final dose of 60 mcg per meal. It is recommended the drug be administered only prior to major meals consisting of 250 calories or 30 grams of carbohydrate. Prandial insulin doses both for those receiving their insulin as MDI or CSII need to be reduced due to a reduction of food intake and the delay in gastric emptying. For those receiving insulin via a pump, most clinicians have found using an “extended bolus” (see above) works best to avoid postprandial hypoglycemia. For those using MDI, some patients administer their insulin just prior to eating (without a lag time) or after eating. Others have found smoother postprandial glycemia using preprandial regular insulin in place of a rapid-acting analogue. Although the package insert suggests reducing the dose by 50%, many have found this too large of a reduction for those receiving appropriate basal insulin and a 25% reduction works well for most. Alternatively, the initial insulin dose reduction might be 25%, increasing to 40 or 50% reduction as the pramlintide dose increases from 15 mcg to 60 mcg before each meal. Due to the mechanism of action of pramlintide noted above, weight loss is common and mean weight loss after 6 months of 1 to 2 kg is the norm. However, this effect is quite variable and weight losses of 5 to 10 kg have been reported.

The major side effect of pramlintide is nausea, or more accurately, a post-prandial feeling of abdominal fullness. In the registration studies, where nausea was routinely questioned for, some nausea was noted in 30 to 40% of patients. The nausea is most often mild and self-limited. The most important practical point is that if nausea occurs one should not titrate the dose upwards until the nausea resolves. Some patients require extremely slow titration, no more than 6 mcg dose increments per week (1 unit on an insulin syringe).

Severe hypoglycemia has also been noted with the use of pramlintide. In the open-label clinical trials with prandial insulin reduction, severe hypoglycemia was reported in 2.3% and 0.9% of patients in the first three and subsequent three months respectively. However, this can be minimized by ensuring proper basal insulin dosing (both CSII and MDI) prior to initiation. Frequent post-meal glucose testing will also reduce the frequency of post-meal hypoglycemia.