Section 01
What it's used for
Approved add-on diabetes drug
Approved by the FDA (as Symlin) alongside mealtime insulin in diabetes. It lowers a blood-sugar marker (HbA1c) by 0.3-0.6% and, unusually for a diabetes drug, brings 1-3 kg of weight loss instead of the weight gain most medicines cause.
▸Clinical wording
FDA-approved as Symlin for adjunctive use with mealtime insulin. Reduces HbA1c by 0.3-0.6% with concurrent weight loss of 1-3 kg (unusual for diabetes medications which typically cause weight gain).
Weight loss in clinical studies
In studies combining it with lifestyle coaching, pramlintide produced consistent weight loss of 3-7% of body weight. Combined with the drug phentermine, weight loss reached up to 11%, both figures from clinical research, not everyday use.
▸Clinical wording
Pramlintide demonstrates consistent weight loss of 3-7% when combined with behavioral interventions. It was studied in combination with phentermine showing up to 11% weight loss.
Section 02
Mechanism of Action
A receptor assembled from two parts
- Amylin has no receptor gene of its own; one is built from a calcitonin receptor plus a helper protein.
- Adding either of two helper proteins in cells created amylin binding sites, while a third one did not.
- Swapping helper parts showed its outer end sets the pharmacology and the rest sets surface delivery.
- The resulting receptor subtypes signal mainly through cAMP, with other internal signals also reported.
▸Clinical wording
Amylin receptors formed by the calcitonin receptor and RAMPs
Amylin has no receptor gene of its own. Co-transfecting COS-7 cells with the human calcitonin receptor and RAMP1 or RAMP3 generated specific rat-amylin binding sites with two distinct pharmacological phenotypes, while RAMP2 or empty vector did not; cAMP responses tracked the binding phenotypes (Christopoulos, Mol Pharmacol 1999). Chimeric RAMP experiments showed the RAMP amino terminus sets the phenotype while its transmembrane and carboxy-terminal domains set how much receptor reaches the surface (Zumpe, BBRC 2000). The resulting AMY1, AMY2 and AMY3 subtypes couple mainly to cAMP, with ERK1/2 phosphorylation and calcium mobilisation also reported (Bower and Hay, Br J Pharmacol 2016).
Three swaps that stop clumping
- Fragments of human and cat amylin formed amyloid-like fibres in a dish, while rodent versions did not.
- Swapping a single amino acid in the sticky core almost abolished fibre formation.
- Pramlintide is human amylin carrying three rodent-type prolines, removing fibre formation and toxicity while keeping receptor activity.
- The trade-off is that it must be buffered near pH 4 to stay dissolved.
▸Clinical wording
Proline substitutions that block amyloid fibril formation
Synthetic peptides matching residues 20-29 of human and cat islet amyloid polypeptide formed amyloid-like fibrils in vitro, whereas the same segments from three rodent species that never develop islet amyloid did not; Ala-Ile-Leu-Ser-Ser at positions 25-29 was the amyloidogenic core, and a proline-for-serine swap at position 28 almost abolished fibril formation (Westermark, PNAS 1990). Pramlintide is human amylin carrying exactly those rodent-type prolines at positions 25, 28 and 29, which removes amyloid formation and cytotoxicity while preserving receptor activity; the trade-off is that it must be buffered near pH 4 to stay soluble (Bower and Hay, Br J Pharmacol 2016).
A brain area open to the bloodstream
- The area postrema sits outside the blood-brain barrier and reads blood-borne signals directly.
- Destroying that area in rats significantly reduced the appetite-suppressing response to injected amylin.
- In rat brain slices amylin excited 48 percent of the neurons tested at near-physiological concentrations.
- Those neurons were fifteen times more sensitive than neurons of a neighbouring brain structure.
▸Clinical wording
Area postrema as the site of action for circulating amylin
The area postrema lies outside the blood-brain barrier and reads blood-borne signals directly. Thermal ablation of the area postrema and nucleus of the solitary tract in rats significantly reduced the anorectic response to intraperitoneal amylin (Lutz, Peptides 1998). In rat brain slices, amylin at 10E-11 to 10E-8 M excited 48 percent of 94 area postrema neurons with a mean threshold near 10E-10 M, close to physiological plasma levels, and these neurons were fifteen-fold more sensitive than subfornical organ neurons; the antagonist AC-187 blunted the response, c-Fos work confirmed it in vivo, and cGMP acted as the excitatory second messenger (Riediger, Am J Physiol 2001).
Slower stomach emptying and less glucagon
- In healthy volunteers pramlintide raised stomach emptying half-time from 112 minutes to 169 and 177 minutes.
- Small bowel and colon transit were unchanged, while a marker of vagus nerve output fell.
- In two blinded placebo-controlled trials in type 1 diabetes, the meal-driven rise in glucagon was absent on pramlintide.
▸Clinical wording
Vagal slowing of gastric emptying and suppression of meal glucagon
In healthy humans randomised to placebo or subcutaneous pramlintide, gastric emptying half-time rose from 112 minutes to 169 and 177 minutes, while small bowel and colonic transit were unchanged; postprandial pancreatic polypeptide, a marker of vagal cholinergic outflow, fell and correlated inversely with emptying half-time, pointing to vagal inhibition (Samsom, Am J Physiol 2000). In two randomised double-blind placebo-controlled studies in type 1 diabetes, plasma glucagon rose after a standardised liquid meal in the placebo-plus-insulin group but not in any pramlintide arm, whether infused intravenously or injected subcutaneously (Fineman, Metabolism 2002).
Eating less at the next meal
- A single injection before a preload meal cut buffet calorie intake by 202 kcal in men with type 2 diabetes.
- The same test cut intake by 170 kcal in non-diabetic obese men without changing meal duration.
- Hunger ratings and gut hormone profiles suggested a direct fullness effect rather than recruitment of other appetite hormones.
- In obese rats, combining amylin with leptin produced synergistic reductions in food intake and body weight.
▸Clinical wording
Satiation, food intake and interaction with leptin signalling
Given as a single subcutaneous dose before a preload meal, pramlintide cut ad libitum buffet energy intake by 202 kcal in insulin-treated men with type 2 diabetes and by 170 kcal in non-diabetic obese men, without changing meal duration; hunger ratings and plasma CCK, GLP-1 and PYY profiles suggested a primary satiogenic action rather than recruitment of other anorexigenic gut peptides (Chapman, Diabetologia 2005). In diet-induced obese rats, amylin and leptin infused together produced formally synergistic reductions in food intake and body weight, with fat loss twice that of pair-fed controls and no compensatory fall in energy expenditure (Trevaskis, Endocrinology 2008).
Section 03
Biological Pathways
- CTR/RAMP receptor assemblyAmylin has no receptor gene of its own; co-transfecting cells with the calcitonin receptor plus RAMP1 or RAMP3 generated AMY1/AMY3 phenotypes coupling mainly to cAMP, while RAMP2 did not (Christopoulos 1999).
- Proline substitutions block fibrilsPramlintide carries rodent-type prolines at positions 25, 28 and 29 of human amylin, a swap that nearly abolished amyloid fibril formation and cytotoxicity while preserving receptor activity (Westermark 1990).
- Area postrema signal detectionThis blood-brain-barrier-free brainstem site reads circulating amylin directly: rat neurons were excited near physiological plasma levels, and ablation blunted the anorectic response (Lutz 1998; Riediger 2001).
- Vagal slowing of gastric emptyingSubcutaneous pramlintide raised gastric emptying half-time from 112 to 169-177 minutes in healthy humans; falling pancreatic polypeptide pointed to vagal inhibition (Samsom 2000).
- Satiation and meal glucagon suppressionPramlintide cut ad libitum buffet intake by 170-202 kcal in obese and diabetic men without lengthening meals, and blocked the postprandial glucagon rise seen with placebo (Chapman 2005; Fineman 2002).
Section 04
Dosage Information
Lys-Cys-Asn-Thr-Ala-Thr-Cys-Ala-Thr-Gln-Arg-Leu-Ala-Asn-Phe-Leu-Val-His-Ser-Ser-Asn-Asn-Phe-Gly-Pro-Ile-Leu-Pro-Pro-Thr-Asn-Val-Gly-Ser-Asn-Thr-Tyr-NH2| Route / system | Context | Range studied | Limitation |
|---|---|---|---|
| Subcutaneous — type 1 diabetes | Official label (Symlin), added to mealtime insulin | 15 µg before each meal of 250 kcal or 30 g carbs, then 15 µg steps no sooner than every 3 days, to 30 or 60 µg | Halving the mealtime insulin is not optional. The label's strongest warning is severe low blood sugar within 3 hours of the shot, in type 1 above all. |
| Subcutaneous — type 2 diabetes | Official label (Symlin), added to mealtime insulin | 60 µg before each main meal, raised to 120 µg after three days without marked nausea; mealtime insulin halved | Four times the type 1 starting dose of the same drug: the number follows the diagnosis, not body weight. Nausea sets the ceiling and pushes the dose back. |
| Subcutaneous — obesity, no diabetes | Phase 2 dose-finding in obese adults, 4 and 12 months | 120, 240 or 360 µg two or three times a day before meals in 411 adults; the best arms lost 6.1 kg and 7.2 kg more than placebo | Trial doses that never became a label — not approved for weight, programme dropped. These arms ran with lifestyle change and no insulin to cut. |
| Subcutaneous — anything obtained today | Withdrawn in the US; no licensed product is left | No current dose. The pens gave fixed steps: SymlinPen 60 gave 15, 30, 45 and 60 µg, SymlinPen 120 gave 60 and 120 µg | Every Symlin form is discontinued in the US. Without those steps a 15 µg increment is drawn by hand — for the drug whose label halves insulin. |
Results
Syringe Fill Level (100u syringe)
Set positive values for: Recommended dose per kg.
Research Use Only. This information is for educational and research purposes only. Not intended for medical advice or self-medication.
Section 05
Protocols
No protocols featuring this peptide yet. Browse All Protocols
Section 06
Stability & Storage
Storing the product
Symlin pens are stored at 2–8 °C before use. The proline substitutions in pramlintide's sequence prevent the amyloid aggregation that would otherwise occur at physiological concentrations.
After opening
Once opened, a pen is kept at room temperature (up to 25 °C) or refrigerated, and used within 30 days. It is not frozen at any stage.
Section 07
Side Effects & Precautions
Nausea is the most common side effect (30-50% initially), typically resolving over 2-4 weeks with gradual dose titration. Severe hypoglycemia can occur, particularly in type 1 diabetes — insulin dose reduction of 50% is recommended when initiating pramlintide. Anorexia, vomiting, abdominal pain. Injection site reactions.
Section 08
Regulatory Status
FDA / United States
Approved 2005, discontinued 2025
Symlin (SymlinPen 60/120) was cleared as an adjunct to mealtime insulin for type 1 and type 2 diabetes. AstraZeneca discontinued manufacturing, and the last formulations left the US market around October 2025; no generic pramlintide ever reached the market.
EMA / Europe
Never approved
Pramlintide has never held a European marketing authorisation and was not available through standard EU prescribing even while Symlin was sold in the US.
WADA
Not prohibited
Pramlintide and other amylin analogues do not appear in the peptide-hormone (S2) or metabolic-modulator (S4) sections of the 2026 Prohibited List.
Regulatory status differs by country and changes over time. A manufacturer's decision to discontinue a drug reflects commercial choices, not necessarily a safety withdrawal — check current availability before relying on this entry.
Section 09
Research Studies
- [1]Multiple amylin receptors arise from receptor activity-modifying protein interaction with the calcitonin receptor gene productChristopoulos G, Perry KJ, Morfis M, Tilakaratne N, Gao Y, Fraser NJ, Main MJ, Foord SM, Sexton PM. · Molecular Pharmacology · 1999
- [2]Multiple RAMP domains are required for generation of amylin receptor phenotype from the calcitonin receptor gene productZumpe ET, Tilakaratne N, Fraser NJ, Christopoulos G, Foord SM, Sexton PM. · Biochemical and Biophysical Research Communications · 2000
- [3]Amylin structure-function relationships and receptor pharmacology: implications for amylin mimetic drug developmentBower RL, Hay DL. · British Journal of Pharmacology · 2016
- [4]Islet amyloid polypeptide: pinpointing amino acid residues linked to amyloid fibril formationWestermark P, Engstrom U, Johnson KH, Westermark GT, Betsholtz C. · Proceedings of the National Academy of Sciences · 1990
- [5]Lesion of the area postrema/nucleus of the solitary tract (AP/NTS) attenuates the anorectic effects of amylin and calcitonin gene-related peptide (CGRP) in ratsLutz TA, Senn M, Althaus J, Del Prete E, Ehrensperger F, Scharrer E. · Peptides · 1998
- [6]Amylin potently activates AP neurons possibly via formation of the excitatory second messenger cGMPRiediger T, Schmid HA, Lutz T, Simon E. · American Journal of Physiology - Regulatory, Integrative and Comparative Physiology · 2001
- [7]Pramlintide, an amylin analog, selectively delays gastric emptying: potential role of vagal inhibitionSamsom M, Szarka LA, Camilleri M, Vella A, Zinsmeister AR, Rizza RA. · American Journal of Physiology - Gastrointestinal and Liver Physiology · 2000
- [8]The human amylin analog, pramlintide, corrects postprandial hyperglucagonemia in patients with type 1 diabetesFineman MS, Koda JE, Shen LZ, Strobel SA, Maggs DG, Weyer C, Kolterman OG. · Metabolism · 2002
- [9]Effect of pramlintide on satiety and food intake in obese subjects and subjects with type 2 diabetesChapman I, Parker B, Doran S, Feinle-Bisset C, Wishart J, Strobel S, Wang Y, Burns C, Lush C, Weyer C, Horowitz M. · Diabetologia · 2005
- [10]Amylin-mediated restoration of leptin responsiveness in diet-induced obesity: magnitude and mechanismsTrevaskis JL, Coffey T, Cole R, Lei C, Wittmer C, Walsh B, Weyer C, Koda J, Baron AD, Parkes DG, Roth JD. · Endocrinology · 2008
- [11]Amylin: pharmacology, physiology, and clinical potentialHay DL, Chen S, Lutz TA, Parkes DG, Roth JD. · Pharmacological Reviews · 2015
Section 10
Frequently Asked Questions
Pramlintide is a synthetic analog of amylin, a hormone normally co-released with insulin from pancreatic beta cells. It acts on amylin receptors — the calcitonin receptor paired with accessory proteins called RAMPs — including in the area postrema, a brainstem region that reads blood-borne signals directly, and through that pathway slows gastric emptying, suppresses post-meal glucagon release, and increases satiety.
Weight loss, unusual for a diabetes medication since most cause gain. As an insulin adjunct for diabetes it produced 1 to 3 kg of weight loss alongside HbA1c reductions of 0.3 to 0.6%. In a phase 2 trial in obese adults without diabetes, higher-dose arms lost 6.1 to 7.2 kg more than placebo over 4 to 12 months, but pramlintide was never approved for weight loss on its own.
Yes, and it's the label's strongest warning, particularly in type 1 diabetes: severe low blood sugar can occur within 3 hours of injection. Because of this, the mealtime insulin dose is cut by half when pramlintide is started.
The approved label started type 1 diabetes patients at 15 µg before each meal, raised in 15 µg steps no sooner than every 3 days up to 30 or 60 µg, alongside a 50% cut in mealtime insulin. Type 2 diabetes patients started higher, at 60 µg per meal, raised to 120 µg after three days if nausea wasn't marked.
The sourcing here doesn't give a stated reason from the manufacturer — only that every Symlin form, including the fixed-dose SymlinPen 60 and SymlinPen 120 injectors, has been withdrawn from the US market, leaving no licensed pramlintide product available there.
They act on different hormone systems: pramlintide mimics amylin, semaglutide mimics GLP-1, and both slow gastric emptying and reduce appetite through separate receptors. Pramlintide is approved only as an add-on to mealtime insulin in diabetes, with a required insulin cut at the start, while GLP-1 drugs are used with or without insulin and are also approved for weight management on their own.
Nausea is the most common effect, hitting 30 to 50% of people initially, though it typically eases over 2 to 4 weeks as the dose is raised gradually. Beyond nausea and the hypoglycemia risk, the label lists anorexia, vomiting, abdominal pain and injection-site reactions.