What is Pramlintide?
As a synthetic amyloid peptide analogue, pramlintide functions as an insulin supplement primarily for patients diagnosed with type 1 and type 2 diabetes. The drug enhances glycemic management through its insulin and GLP-1 mimicking effects and produces weight-loss results.
Table.1 Pramlintide related products at Creative Peptides.
Pramlintide Structure
The sequence design of pramlintide comes from rat amyloid peptide rather than human amyloid islet polypeptide which creates a structural difference from natural amyloid peptide. The proline residues at positions 25, 28, and 29 in pramlintide have been replaced to enhance its pharmacological effectiveness. As a non-amyloid protein, pramlintide remains stable and safe because it avoids forming amyloid fibers. The disulfide bond connects Cys2 and Cys3 which represents a typical structural characteristic of many proteins.
Fig.1 The arrangement of 37 amino acids in the pramlintide.
Pramlintide Functions
Pramlintide is an effective adjunct to the treatment of diabetes, improving glycemic control, promoting weight management, and providing potential cardiovascular protection through multiple mechanisms. The following are the main functions of pramlintide:
Lowers postprandial blood glucose levels: Pramlintide lowers postprandial blood glucose levels by inhibiting postprandial glucagon secretion, delaying gastric emptying, and suppressing appetite. Together, these effects reduce glucose production in the liver and lower food intake, which contributes to overall blood sugar control.
Improved efficacy of insulin therapy: Pramlintide is often used as an adjunct to insulin therapy, especially in patients with type 1 and type 2 diabetes. It reduces insulin use while improving glycemic control without increasing the risk of hypoglycemia.
Weight management: Pramlintide helps reduce food intake by suppressing appetite and slowing gastric emptying, thereby promoting weight loss. In clinical trials, pramlintide significantly reduced the weight of obese patients.
Cardiovascular protection: Pramlintide has also shown certain cardiovascular protective effects, such as reducing levels of oxidative stress markers and reducing postprandial blood glucose fluctuations, which may reduce the risk of diabetes-related complications.
Table.2 Cardiovascular disease (CVD) related peptides at Creative Peptides.
Mechanism of Action
Pramlintide's mechanism of action improves glycemic control primarily by mimicking an insulin-like peptide (Amylin). The following is a detailed description of the mechanism of action of pramlintide:
Delayed gastric emptying: Pramlintide slows the rate of emptying of gastric contents by activating neural mechanisms in the gastrointestinal tract. This effect can extend the length of time food stays in the stomach, which slows the rate at which blood sugar rises after a meal.
Inhibition of glucagon secretion: Pramlintide can reduce the secretion of glucagon after meals, thereby reducing the decomposition of glycogen in the liver and the production of new glucose, further reducing blood sugar levels.
Increases satiety: Pramlintide increases the patient's satiety by activating satiety-related areas in the central nervous system, thereby reducing food intake and aiding in weight management.
Multiple mechanisms of action synergistic: Pramlintide not only improves glycemic control through the above mechanisms, but also provides a more comprehensive glycemic regulatory effect when combined with other glucose-lowering drugs such as insulin or metformin.
Safety features: Pramlintide does not cause hypoglycemia, especially when used alone. When used in combination with insulin, its dose needs to be adjusted appropriately to avoid the risk of hypoglycemia.
Other potential effects: In addition to the main mechanisms mentioned above, pramlintide may also exert other biological effects by modulating oxidative stress responses, such as showing certain anti-inflammatory and anti-tumor potential in patients with diabetes and obesity.
Pramlintide effectively improves postprandial blood glucose levels by delaying gastric emptying, inhibiting glucagon secretion, increasing satiety, and other mechanisms, and has shown good safety and synergistic effects in combination therapy.
Table.3 Insulin related products at Creative Peptides.
Pharmacokinetics and Metabolism
Pancreatic amyloid polypeptide is a polypeptide hormone made up of 37 amino acid residues. It is released by pancreatic beta cells after meal. It has been proved that pramlintide can delay the absorption of glucose, inhibit the secretion of glucagon and reduce the formation and release of liver sugar, thus it can reduce the frequency and amplitude of blood glucose fluctuation and improve the overall blood glucose control in diabetic patients. The absolute bioavailability of pramlintide peptide is 30% to 40%, the peak time is about 20 minutes, and the half-life is about 50 minutes. pramlintide is mainly metabolized and excreted by the kidney. The half-life of its metabolite Des-lyspramlintide is similar to that of pramlintide.
Pramlintide and Diabetes
Pramlintide is a synthetic insulin-like peptide primarily used in the treatment of diabetes mellitus, where its main mechanisms of action include delaying gastric emptying, inhibiting glucagon secretion, and generating satiety through the central nervous system, thereby improving glycemic control and weight management. The following are the specific applications of pramlintide in different diseases.
Pramlintide and Type 1 Diabetes
Pramlintide is approved as an adjunct to insulin therapy for those with type 1 diabetes who are on insulin but have poor glycemic control. Studies have shown that pramlintide can significantly improve blood sugar control, lower HbA1c (Glycated Hemoglobin A1c) levels, and reduce insulin doses. For example, in a one-year study, patients in the pramlintide group experienced an average decrease in HbA1c levels of 0.3 to 0.4 percent, along with weight loss. Pramlintide can also reduce postprandial blood sugar fluctuations and improve the overall quality of life of patients. However, it is important to note that pramlintide, when used in combination with insulin, may increase the risk of hypoglycemia.
Pramlintide and Type 2 Diabetes
Pramlintide can be used as a premeal insulin supplement, in combination with insulin, metformin, or sulfonylureas to improve glycemic control and weight management. Studies have shown that pramlintide significantly reduces HbA1c and body weight.
Table.4 Peptides in diabetes at Creative Peptides.
Other Therapeutic Applications
In addition to diabetes and oncology treatment, pramlintide has demonstrated potential in other areas:
Pramlintide and Weight Loss
Pramlintide is mainly used for blood sugar control in diabetics, but studies in recent years have shown that it also has some weight loss effects. Pramlintide achieves its weight loss effect by mimicking the action of natural insulin-like peptides mainly through the following mechanisms.
Slows down gastric emptying: Pramlintide slows down gastric emptying, thereby increasing satiety and reducing food intake.
Inhibits glucagon secretion: It can inhibit the secretion of glucagon after meals, further reducing appetite.
Regulates appetite: Pramlintide acts through the central nervous system, reducing hunger and enhancing satiety.
Several studies have shown that pramlintide can lead to significant weight loss in obese or overweight patients:
In a 6-week randomized, double-blind, placebo-controlled trial in which 60 obese subjects received different doses of pramlintide injections, the results showed an average weight loss of 2.6 kg. In another 24-week study, 177 obese subjects were treated with pramlintide and lost 2.8 kilograms. In a 52-week study, 656 patients with type 2 diabetes who were treated with pramlintide lost an average of 1.5 kilograms.
When pramlintide is used in combination with other drugs, the weight loss effect is more significant:
In one study, pramlintide in combination with meglitinide resulted in a 12.75% weight loss in obese patients, significantly higher than the effect of pramlintide or meglitinide alone.
Another study showed that pramlintide in combination with phentermine reduced the average weight of obese patients by 11.5 kilograms.
Pramlintide and Antitumor
Recent studies have found that pramlintide has potential anti-tumor activity, especially in colorectal cancer (CRC). Pramlintide has been shown to inhibit the growth of HCT-116 and HT-29 cells and work synergistically with chemotherapy drugs such as 5-fluorouracil, oxaliplatin, and irinotecan to enhance chemotherapy efficacy.
Pramlintide and Alzheimer's Disease (AD)
Studies have shown that pramlintide can improve cognitive function and pathological status in Alzheimer's disease model mice, possibly related to its antioxidant stress mechanism.
Pramlintide and Metabolic Regulation
Pramlintide also plays a role in regulating energy balance and metabolism, such as improving the survival rate and metabolism of intervertebral disc cells in disc degeneration.
Summary
Pramlintide serves as an adjunct in managing type 1 and type 2 diabetes by improving glycemic control, promoting weight loss, and offering cardiovascular protection. Its mechanism includes delaying gastric emptying, inhibiting glucagon secretion, and enhancing satiety. The drug also helps reduce insulin use, minimizing hypoglycemia risks. Beyond diabetes, pramlintide has shown potential in weight loss, anticancer activity, and even Alzheimer's treatment. Looking ahead, its multifaceted benefits highlight its promising role in broader metabolic and therapeutic applications, improving both quality of life and clinical outcomes for various conditions.
FAQs
1. What kind of drug is pramlintide?
Pramlintide is an injectable synthetic analog of amylin used to manage blood glucose levels in patients with diabetes by regulating post-meal glucose spikes and enhancing satiety.
2. Is pramlintide an amylin?
Pramlintide is not amylin itself but a synthetic analog of human amylin, mimicking its physiological functions to assist in glucose regulation alongside insulin therapy.
3. What is the onset of action with pramlintide?
Pramlintide has a rapid onset of action, typically beginning within 20 minutes after subcutaneous injection, making it effective for controlling postprandial glucose levels.
4. Is pramlintide a peptide?
Yes, pramlintide is a peptide consisting of 37 amino acids. Its structure closely resembles human amylin, allowing it to function similarly in glucose regulation.
Reference
- Ryan, Gina J., et al., Pramlintide in the treatment of type 1 and type 2 diabetes mellitus. Clinical therapeutics 27.10 (2005): 1500-1512.
