In 2005, a small pharmaceutical company obtained FDA approval to sell the first non-insulin product for type 1 diabetes as well as for use in type 2 diabetes. The company, Amylin Pharmaceuticals, had developed their drug, Symlin (pramlintide acetate), over 16 years of effort, and found that it improves postprandial glucose, and allows weight loss, less insulin use, and minimization in glucose fluctuations.
Pramlintide is a synthetic version of a hormone that almost no one has heard of: amylin. Amylin the hormone is a polypeptide that is synthesized by the beta cells of the pancreas. The beta cells, well-known as the body's factory that produces insulin, apparently have been multitasking and making amylin all along. Amylin (sometimes called Islet Amyloid Polypeptide or IAPP) is released in response to meals, and has several roles: modifying the rate of gastric emptying; prevention of the postprandial rise in the hormone glucagon; and satiety leading to decreased caloric intake and potential weight loss. The end result, when given with insulin, is to help control glucose levels.
However, the clinical trials for Symlin showed that decreases in A1C were minimal, and the FDA was concerned about cases of severe hypoglycemia that had been seen in the clinical trials. Amylin agreed to refrain from advertising Symlin for a year after launch, and hired a marketing agency to try to figure out how to promote the product.
Despite the agency's glowing claims that they "built an identity and launch platform for Symlin as a symbiotic brand with its own unique benefits independent of insulin" with baloney like "We positioned the efficacy of Symlin outside of the diabetes benchmark of A1C with 'Benefits Beyond A1C'," sales of Symlin never took off.
Meanwhile, Amylin obtained approval for another diabetes drug (Byetta, exenatide), and refocused its attention on selling the newer drug, and on developing a once-weekly version of Byetta. Symlin sort of disappeared from everyone's view, and Symlin sales slumped.
What was wrong with Symlin? Superficially, it might seem that a non-insulin drug that's approved for use in both type 1 and type 2 diabetes should be a winner. But the drawbacks are overwhelming:
- the drug is approved only when given together with mealtime insulin.
- the drug has to be given by injection. Which raises an interesting question: why would anyone want to have to give injections of two different products at mealtime, when one (insulin) is well-known to control glucose and the other (pramlintide) is new, the mechanisms of action are obscure, and it doesn't do much to control glucose?
- the drug has a "boxed warning" about hypoglycemia. "Boxed warnings" are the FDA's method of alerting physicians to side effects that are of great concern, and are black-lined boxes at the beginning of the product label. For pramlintide, the warning reads: "WARNING. SYMLIN is used with insulin and has been associated with an increased risk of insulin-induced severe hypoglycemia, particularly in patients with type 1 diabetes.
hypoglycemia associated with SYMLIN use occurs, it is seen within 3 hours following a SYMLIN injection.
If severe hypoglycemia occurs while operating a motor vehicle, heavy
machinery, or while engaging in other high-risk activities, serious injuries may occur.
Appropriate patient selection, careful patient instruction, and insulin dose adjustments are critical elements for reducing this risk."
- the drug's label includes a long list of diabetes patients who are not candidates for the product: those with "poor compliance with current insulin regimen;
poor compliance with prescribed self-blood glucose monitoring;
have an HbA1c >9%;
recurrent severe hypoglycemia requiring assistance during the past 6 months;
presence of hypoglycemia unawareness;
confirmed diagnosis of gastroparesis; require the use of drugs that stimulate gastrointestinal motility;
Should patients using mealtime insulin be advised to use Symlin? Well, maybe, if they aren't on the long list of folks who aren't candidates; if they understand the risk of hypoglycemia and are instructed in how to manage it; if their insulin doses are adjusted when starting Symlin; and if they are willing to inject two different medications at mealtime.
Probably not too many people with diabetes fit this profile. Hence Symlin will remain a niche product, an interesting concept for endocrinologists to consider using for a few patients, but a product that will never be widely used.