Pramlintide is a synthetic version of amylin, a hormone that the pancreas releases together with insulin after meals. It was sold as Symlin (later the SymlinPen) and is an amylin-based drug: the FDA approved it in March 2005 as an add-on to mealtime insulin in type 1 and type 2 diabetes. It is injected under the skin before each major meal, up to three or four times a day.
Pramlintide slows stomach emptying, blunts the after-meal rise in glucagon and reduces appetite, so it lowers post-meal blood sugar and causes modest weight loss. It was also tested as an obesity drug but was never approved for that use. Two facts matter most: the label carries a boxed warning for severe hypoglycemia when it is combined with insulin, and in October 2025 the manufacturer notified the FDA that it was discontinuing manufacture of the SymlinPen; FDA’s database now lists all Symlin products as discontinued.
This page summarizes what the FDA label, clinical trials and regulators report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Amylin analog (synthetic 37-amino-acid peptide) |
| Brand / approval | Symlin / SymlinPen, developed by Amylin Pharmaceuticals, now AstraZeneca; NDA 021332, approved March 16, 2005 |
| Route | Subcutaneous injection immediately before major meals |
| Strengths | 1000 mcg/mL pens: SymlinPen 60 (1.5 mL) and SymlinPen 120 (2.7 mL) |
| Labeled doses | Type 1 diabetes: 15 mcg titrated to 30–60 mcg per meal; type 2 diabetes: 60 mcg titrated to 120 mcg per meal |
| Half-life (label) | About 48 minutes in healthy people |
| Boxed warning | Severe hypoglycemia when used with insulin, mainly in type 1 diabetes |
| US status | Prescription drug; manufacture discontinued (FDA notice October 2025); not approved for weight loss |
| WADA status | Not named on the 2026 Prohibited List |
What it is
Amylin was isolated in 1987 from the amyloid deposits found in the pancreas of people with type 2 diabetes. It is a 37-amino-acid peptide related to calcitonin gene-related peptide (Cooper et al., PNAS 1987). Beta cells store amylin in the same granules as insulin and release both hormones together after food. In type 1 and type 2 diabetes, the meal-time release of both is reduced (FDA label).
Human amylin itself is a poor drug because it clumps into insoluble amyloid fibrils. Pramlintide keeps the 37-residue length of human amylin but replaces three amino acids (positions 25, 28 and 29) with proline (FDA label). Rat amylin, which does not form fibrils, carries prolines at these sites. Proline disrupts the beta-sheet structure that fibrils need, which makes pramlintide soluble and non-aggregating (Chiu et al., Biophys J 2013; Weyer et al., Curr Pharm Des 2001). It is supplied as the acetate salt, a white water-soluble powder with a molecular weight of 3949.4, in a solution at pH ≈ 4.0.
How it works
The label describes three effects in people, all aimed at the after-meal period (FDA label):
- Slower gastric emptying (the rate at which food leaves the stomach), without reducing total nutrient absorption.
- Less glucagon after meals. Glucagon tells the liver to release glucose; insulin alone does not normalize this rise in diabetes.
- More satiety. A single dose given 1 hour before an unlimited buffet cut calorie intake by ≈ 21% (30 mcg, type 1 diabetes) and ≈ 23% (120 mcg, type 2 diabetes) versus placebo.
Pramlintide alone does not cause hypoglycemia. In controlled hypoglycemia tests it did not change the body’s counter-regulatory hormone response or the perception of hypoglycemia symptoms.
Pramlintide versus newer amylin analogs
Pramlintide’s short half-life is why it must be injected before every meal. Newer amylin analogs were designed to fix this. Cagrilintide is a lipidated, long-acting analog dosed once weekly, developed partly because pramlintide “requires three daily injections due to its short half-life” (Kruse et al., J Med Chem 2021). Cagrilintide is investigational, mainly studied with semaglutide for obesity, whereas pramlintide is an FDA-approved drug.
Pharmacokinetics
From the FDA label, after single subcutaneous doses in healthy people (abdomen or thigh):
| Dose | Peak level (Cmax) | Time to peak | Elimination half-life |
|---|---|---|---|
| 30 mcg | 39 pmol/L | 21 min | 55 min |
| 60 mcg | 79 pmol/L | 20 min | 49 min |
| 90 mcg | 102 pmol/L | 19 min | 51 min |
| 120 mcg | 147 pmol/L | 21 min | 48 min |
Other label facts:
- Bioavailability after subcutaneous injection is about 30–40%. Exposure rises in proportion to dose.
- Injection site matters. Injection into the arm gave 20–36% higher exposure with much greater variability, so the label advises the abdomen or thigh.
- Protein binding is low; about 40% circulates unbound.
- Metabolism. The main metabolite (pramlintide lacking its first amino acid) is active in the lab. Exposure is stable with repeat dosing, so it does not accumulate.
- Kidneys. Mild to severe renal impairment did not significantly change exposure; end-stage kidney disease was not studied. Liver impairment was not studied.
Pramlintide peaks about 20 minutes after injection, while mealtime insulins generally peak later. This mismatch, plus the need for separate injections, is a recognized barrier to use (Kommera et al., J Pharmacol Exp Ther 2024). Pramlintide and insulin must never be mixed in one syringe: in label studies, premixing changed pramlintide peak levels by up to −40% and total exposure by up to +36%.
Approved medical use
Symlin is indicated as an add-on for people with type 1 or type 2 diabetes who use mealtime insulin and have not reached their glucose goals despite optimal insulin therapy (FDA label). It is not approved for weight loss, for people with diabetes who do not use insulin, or for children.
The labeled scheme is built around hypoglycemia prevention:
| Step | Type 1 diabetes | Type 2 diabetes (on mealtime insulin) |
|---|---|---|
| Mealtime insulin at start | Reduce by 50% | Reduce by 50% |
| Starting dose | 15 mcg before each major meal | 60 mcg before each major meal |
| Titration | 15 mcg steps to 30, 45 or 60 mcg | Increase to 120 mcg |
| Pace | At least 3 days without significant nausea between steps | At least 3 days without significant nausea |
| If not tolerated | Drop to 30 mcg; consider stopping if 30 mcg is not tolerated | Drop back to 60 mcg |
A “major meal” in the label is at least 250 kcal or at least 30 g of carbohydrate. The label says it should be used only by patients who can manage insulin adjustments and frequent glucose monitoring, under a clinician skilled in insulin use. It lists people who should not be considered, including those with an HbA1c over 9%, recurrent severe hypoglycemia in the past 6 months, hypoglycemia unawareness, gastroparesis, or poor adherence to insulin or glucose monitoring.
Regulatory and market status
- Approval. NDA 021332 was approved on March 16, 2005 (Drugs@FDA via openFDA).
- Discontinuation. FDA’s drug shortage database records an October 27, 2025 notice from AstraZeneca of “discontinuation of the manufacture” of SymlinPen 60 and SymlinPen 120 (FDA drug shortages via openFDA). Drugs@FDA now lists every Symlin product, including an earlier 600 mcg/mL presentation, as discontinued. The notice does not give a reason.
- No generics. Drugs@FDA lists no generic pramlintide product.
- Sport. Pramlintide is not named on the WADA 2026 Prohibited List. It is not an insulin, the S4.4.2 class. The S0 class covers substances with no current regulatory approval for human use.
What the research shows
Type 1 diabetes
Pramlintide’s effect on HbA1c (a measure of average blood sugar over about 3 months) is small. In three 26–52-week placebo-controlled trials in which insulin was kept largely fixed, the placebo-subtracted HbA1c change at 6 months was −0.25 to −0.34 percentage points (FDA label). In one of these, a 52-week trial of 651 patients, HbA1c fell by 0.29% (60 mcg three times daily) and 0.34% (60 mcg four times daily) versus 0.04% on placebo. Body weight fell by 0.4 kg on pramlintide and rose by 0.8 kg on placebo (Ratner et al., Diabet Med 2004).
The trial that used the labeled approach (dose titration plus a 30–50% cut in mealtime insulin) gave a different picture. In this 29-week, double-blind trial of 296 patients, insulin was then adjusted freely in both groups (Edelman et al., Diabetes Care 2006):
| Outcome at week 29 | Pramlintide | Placebo |
|---|---|---|
| HbA1c change (baseline 8.1%) | −0.5% | −0.5% |
| 3-hour post-meal glucose excursion (AUC change) | −175 mg·h/dL | −64 mg·h/dL |
| Body weight change | −1.3 kg | +1.2 kg |
| Insulin dose change | −28% | −4% |
| Nausea | 63% | 36% |
| Severe hypoglycemia (events per patient-year) | 0.57 | 0.30 |
HbA1c improved equally in both arms, but pramlintide reduced after-meal glucose spikes, body weight and insulin needs. Nausea and severe hypoglycemia were more common.
Type 2 diabetes on insulin
In a 52-week, double-blind trial of 656 insulin-treated patients, 120 mcg twice daily lowered HbA1c by 0.68% at week 26 and 0.62% at week 52 from a baseline of 9.1%. This was significantly more than placebo (Hollander et al., Diabetes Care 2003). Weight changed by −1.4 kg versus +0.7 kg on placebo. The label’s two type 2 trials show placebo-subtracted HbA1c reductions of 0.30–0.34 points at 6 months.
A meta-analysis of four type 2 diabetes trials (n = 930) found HbA1c −0.33% (95% CI −0.51 to −0.14) and weight −2.57 kg (95% CI −3.44 to −1.70) versus control. Nausea was about 1.8 times more likely with pramlintide (Singh-Franco et al., Diabetes Obes Metab 2011).
Obesity without insulin treatment
Pramlintide was studied for weight loss at doses above the diabetes label, but it was never approved for this use.
| Trial | Design and n | Dosing | Result |
|---|---|---|---|
| Aronne et al., JCEM 2007 | 16-week RCT, 204 obese adults, no lifestyle program | Up to 240 mcg three times daily | Placebo-corrected weight −3.7% (−3.6 kg) in completers; 31% vs 2% lost ≥ 5% |
| Smith et al., Diabetes Care 2008 | 4-month RCT (411 obese adults) plus 8-month extension, with lifestyle program | 120–360 mcg two or three times daily | At 12 months, placebo-corrected −6.1 kg (120 mcg three times daily) and −7.2 kg (360 mcg twice daily); 40–43% vs 12% lost ≥ 10% |
| Ravussin et al., Obesity 2009 | 24-week RCT, 177 overweight or obese adults, 40% calorie deficit | 360 mcg twice daily, alone or with metreleptin 5 mg twice daily | Weight −8.4% (pramlintide), −8.2% (metreleptin), −12.7% (combination); evaluable n = 93 |
The 12-month extension in Smith et al. included only 146 evaluable subjects, so its estimates are less certain. In the meta-analysis above, the pooled weight change in obese people without diabetes (n = 686, 6–24 weeks) was −2.27 kg (95% CI −2.88 to −1.66) versus control (Singh-Franco et al., 2011).
None of these trials studied lean, trained people or reported effects on muscle or athletic performance. There is no evidence that pramlintide preserves muscle during weight loss.
Other research uses
- Artificial pancreas. In a randomized crossover trial in adults with type 1 diabetes, an automated system delivering rapid insulin plus pramlintide raised time in the target glucose range (3.9–10.0 mmol/L) from 74% to 84% compared with insulin alone. Gastrointestinal symptoms followed 6% of meals versus 0% (Haidar et al., Diabetes Care 2020).
- Co-formulation with insulin. In a 16-week randomized trial of 80 people with type 1 diabetes, ADO09 (an investigational mix of pramlintide and an insulin analog) reduced weight by 2.1 kg relative to insulin lispro, with no change in HbA1c (Andersen et al., Diabetes Obes Metab 2024).
- Post-bariatric hypoglycemia. In an 8-week open-label study after gastric bypass (20 dosed, 14 completed), pramlintide did not change meal-test glucose, insulin or glucagon and did not reduce low glucose readings (Sheehan et al., Diabetes Obes Metab 2022).
Side effects and risks
Boxed warning: severe hypoglycemia
Pramlintide by itself does not lower glucose into the hypoglycemic range. With insulin, however, it raises the risk of severe hypoglycemia (an episode that needs another person’s help or medical treatment), especially in type 1 diabetes. When it occurs, it usually comes within 2–3 hours after the injection. The label warns of serious injury or death if it happens while driving or operating machinery (FDA label).
In the type 1 diabetes trials run without an initial insulin dose cut, severe hypoglycemia was more common on pramlintide in the first 3 months:
| Type 1 diabetes, months 0–3 | Pramlintide + insulin (n = 716) | Placebo + insulin (n = 538) |
|---|---|---|
| Patient-ascertained severe hypoglycemia, % of patients | 16.8% | 10.8% |
| Event rate, per patient-year | 1.55 | 1.33 |
| Medically assisted severe hypoglycemia, % of patients | 7.3% | 3.3% |
In the label’s dose-titration trial, where mealtime insulin was cut at the start, the 0–3-month medically assisted rate was 3.4% versus 2.0%. In type 2 diabetes, patient-ascertained severe hypoglycemia in months 0–3 was 8.2% versus 2.1%. This is why the label requires a 50% cut in mealtime insulin at the start and frequent glucose checks.
Gastrointestinal effects
Nausea is the most common side effect. It is worst at the start and fades over time in most people; slow titration reduces it. Rates from the label’s pooled placebo-controlled trials:
| Adverse reaction | Type 1: pramlintide (n = 716) | Type 1: placebo (n = 538) | Type 2: pramlintide (n = 292) | Type 2: placebo (n = 284) |
|---|---|---|---|---|
| Nausea | 48% | 17% | 28% | 12% |
| Anorexia (loss of appetite) | 17% | 2% | 9% | 2% |
| Vomiting | 11% | 7% | 8% | 4% |
| Headache | — | — | 13% | 7% |
| Fatigue | 7% | 4% | 7% | 4% |
| Dizziness | 5% | 4% | 6% | 4% |
A dash means the reaction was not listed for that population. “Inflicted injury” (bruises, falls, fractures and similar) was also reported more often in type 1 diabetes (14% versus 10%). Pancreatitis and injection-site reactions have been reported after approval.
A single 10 mg dose (83 times the maximum type 2 dose), given to 3 healthy volunteers, caused severe nausea with vomiting, diarrhea, vasodilation and dizziness, but no hypoglycemia.
Interactions
- Insulin. Never mixed in the same syringe; given as separate injections at separate sites.
- Oral drugs. Slower gastric emptying can delay absorption. When fast onset matters (painkillers, antibiotics, oral contraceptives), the label advises taking the oral drug at least 1 hour before or 2 hours after pramlintide. Acetaminophen peak levels fell by 20–29% when given 0–2 hours after a 120 mcg dose. The norgestrel peak from an oral contraceptive fell by about 30%.
- Motility drugs. Not recommended with drugs that change gut motility (such as atropine-type anticholinergics) or slow nutrient absorption (alpha-glucosidase inhibitors).
- Glucose-lowering drugs. Other diabetes drugs, ACE inhibitors, fluoxetine, MAO inhibitors, salicylates, sulfonamide antibiotics and others can increase hypoglycemia risk.
- Beta-blockers and clonidine can mask the warning symptoms of hypoglycemia.
Who should not use it
The label lists three contraindications:
- serious hypersensitivity to pramlintide or its ingredients;
- hypoglycemia unawareness (not feeling the warning signs of low blood sugar);
- confirmed gastroparesis (delayed stomach emptying).
Pens must never be shared, even with a new needle, because of the risk of blood-borne infection. Safety in children has not been established. Pregnancy data in humans are too limited to judge risk. In rats, congenital abnormalities were seen at exposures 10 and 47 times the human dose, but not in rabbits.
Key takeaways
- An approved amylin analog. Pramlintide is human amylin with three proline substitutions that stop it clumping. It was approved in 2005 as an add-on to mealtime insulin.
- Short-acting, meal-by-meal. Its half-life is about 48 minutes, so it is injected before each major meal. Long-acting analogs such as cagrilintide were developed to solve this.
- Modest benefits. HbA1c falls by ≈ 0.3 points versus placebo, with weight loss of about 1–3 kg in diabetes trials and up to ≈ 7 kg placebo-corrected over a year in obesity trials. It was never approved for weight loss.
- Hypoglycemia is the key risk. Combined with insulin, it raises severe hypoglycemia risk within about 3 hours of the dose. This is why the label requires a 50% cut in mealtime insulin.
- Nausea is common. Nausea affected 28–48% of patients in label trials, versus 12–17% on placebo.
- No longer manufactured. AstraZeneca notified the FDA in October 2025 that it was discontinuing manufacture, and FDA lists all Symlin products as discontinued.
Sources
- AstraZeneca Pharmaceuticals LP. SymlinPen (pramlintide acetate) injection, prescribing information. DailyMed.
- U.S. Food and Drug Administration. Drugs@FDA: Symlin (pramlintide acetate), NDA 021332. openFDA.
- U.S. Food and Drug Administration. Drug Shortages database: pramlintide acetate injection (SymlinPen 60 and 120), discontinuation notice of October 27, 2025. openFDA.
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