Pramlintide

Symlin, SymlinPen, AC137, pramlintide acetate

Metabolic & weight

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Note on this profile. Pramlintide is an approved prescription medicine in the United States for people with diabetes who use mealtime insulin. It is not a research-only compound, and it is not approved for weight loss. Use outside a prescription — especially without the insulin dose adjustments described in the label — carries a serious risk of severe low blood sugar.

Summary

Class: Amylin analogue; synthetic 37-amino-acid peptide identical to human amylin except for three proline substitutions (positions 25, 28 and 29, borrowed from rat amylin) that stop it clumping
Mechanism: Replaces the hormone amylin that beta cells normally release with insulin: slows gastric emptying, suppresses post-meal glucagon, and reduces appetite
Routes studied: Subcutaneous, immediately before major meals
Dose range reported: Approved: type 1 diabetes 15 µg before meals, increased in 15 µg steps to 30–60 µg; type 2 diabetes 60 µg, increased to 120 µg. Obesity trials (off-label): 120–360 µg two to three times daily
Half-life: ~48 minutes
Storage: Unopened pens: refrigerate. In-use pen: room temperature (below 30 °C) or fridge, discard after 30 days
Regulatory status: FDA-approved (2005) as an adjunct to mealtime insulin in type 1 and type 2 diabetes. Never approved in the EU, UK or Australia

Doses are as reported in studies or by the community — never recommendations.

1What it is

Amylin is a hormone that healthy beta cells release alongside insulin after a meal. People with type 1 diabetes make neither; people with advanced type 2 diabetes make less of both. Human amylin itself cannot be used as a drug because it aggregates into sticky fibrils (the same amyloid deposits seen in the pancreas in type 2 diabetes). Pramlintide swaps three amino acids for the rat versions, which keeps the hormone's activity while preventing aggregation.

It was developed by Amylin Pharmaceuticals, approved in the US in 2005 and sold as Symlin, later by AstraZeneca. It is the only amylin analogue approved anywhere and remains a niche product because it requires a separate injection before each meal and an insulin dose cut. Its main relevance to this site is as the founding member of the amylin class that now includes cagrilintide (see its own profile), petrelintide (66) and eloralintide (67) — and as the drug that first showed amylin signalling produces weight loss in humans.

2How it's thought to work

Pramlintide acts on amylin receptors, which are calcitonin receptors paired with receptor-activity-modifying proteins (RAMPs), mostly in the brainstem (area postrema) and hypothalamus:

Gastric emptying. slowed, which blunts post-meal glucose rises.

Glucagon. suppresses the abnormal post-meal glucagon surge seen in diabetes (not the protective glucagon response to hypoglycaemia).

Satiety. increases meal-related fullness via the brainstem, reducing food intake and body weight independent of nausea.

Leptin interaction. in rodent and human studies, amylin appears to restore responsiveness to leptin, the fat-derived satiety hormone, which is why it was studied with metreleptin.

A stabilised amylin analogue; native amylin clumps into fibrils and cannot be formulated. Given with insulin at meals, it blunts the glucose rise and reduces the dose needed.Schematic — not to scale

3What the research shows

Glucose control in type 1 diabetes

Year-long placebo-controlled trials in people on insulin found HbA1c reductions of about 0.3–0.4 percentage points with modest weight loss (−0.5 to −1.5 kg) where placebo gained weight (Whitehouse 2002, Diabetes Care; Ratner 2004, Diabet Med). Effects are small by today's standards but came with lower insulin requirements. [1][3]

Glucose control in insulin-treated type 2 diabetes

Similar HbA1c reductions (~0.5–0.6 points) and 1–2 kg weight loss over 52 weeks (Hollander 2003, Diabetes Care). Post-meal glucose excursions and glucose variability improve more than HbA1c suggests. [2]

Graded A (modest), off-label

Weight loss in obesity without diabetes

A 16-week dose-ranging trial in obese adults found placebo-corrected weight loss of about 3–4% at 240–360 µg two to three times daily (Aronne 2007, J Clin Endocrinol Metab). Extended to 52 weeks with lifestyle intervention, weight loss averaged around 7–8% (Smith 2008, Diabetes Care). [4][5]

Graded A/B (development stopped)

Combination with metreleptin

A 24-week proof-of-concept trial of pramlintide plus metreleptin (a leptin analogue) in overweight adults produced about 12.7% weight loss vs ~8% with either alone (Ravussin 2009, Obesity), a striking result for its time. Development of the combination was halted in 2011 after a safety signal involving antibody formation to leptin. [6]

Cardiovascular outcomes

No outcome trial has been conducted. Not required at the time of approval.

4Reported side effects and interactions

Literature-reported

Literature (common). nausea (28–48% early in treatment, dose-related and fading over weeks), reduced appetite, vomiting, headache, fatigue, injection-site reactions.

Other warnings. not for people with gastroparesis, hypoglycaemia unawareness, HbA1c >9%, or poor adherence to monitoring. Not studied in pregnancy.

Community-reported

off-label use for appetite suppression with reports of strong meal-related fullness and nausea; little systematic community experience compared with GLP-1 agents.

Boxed warning — severe hypoglycaemia. pramlintide does not itself cause low blood sugar, but when added to insulin it increases the risk of severe insulin-induced hypoglycaemia, particularly in type 1 diabetes, typically within 3 hours of injection. The label requires a 50% reduction in mealtime insulin doses when starting and careful glucose monitoring. This is the main reason off-label and unsupervised use is dangerous.

Interactions. mealtime insulin (see boxed warning); slows absorption of oral medicines — those needing rapid onset (analgesics, antibiotics) should be taken 1 hour before or 2 hours after; drugs that alter gastric motility (anticholinergics) and alpha-glucosidase inhibitors are not recommended alongside. Pramlintide must not be mixed in the same syringe as insulin (the pH and formulation are incompatible).

Markers researchers commonly monitor

Following the approved-label monitoring:

Marker	Why it's watched
Pre- and post-meal glucose (fingerstick or CGM)	essential; pramlintide changes post-meal patterns and raises insulin-related hypoglycaemia risk in the first 3 hours after injection.
HbA1c	the longer-term efficacy measure.
Insulin dose log	the label's 50% mealtime insulin cut at initiation, then re-titration, needs careful records.
Weight and appetite diary	the effect most relevant to those interested in it as an amylin-class compound.
Hypoglycaemia frequency and awareness	people with hypoglycaemia unawareness are excluded by the label.
eGFR	no dose adjustment to moderate kidney impairment, but not studied in dialysis.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Supplied as a pre-filled multi-dose pen (SymlinPen 60 and 120) needing no ; doses are dialled in micrograms. The solution is acidic (pH ~4), which is why it stings slightly and cannot be co-injected with insulin. Inject at a site at least 5 cm from any insulin injection. pramlintide is not in meaningful grey-market circulation and the calculator does not apply to the approved pen.

Open in calculator, pre-loaded →

6Commonly studied alongside

Mealtime insulin (its approved use), metreleptin (historical combination), metformin and sulfonylureas (type 2 trials). Later amylin analogues — cagrilintide, petrelintide, eloralintide — build directly on its pharmacology.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	FDA-approved (Symlin, 2005) for type 1 and type 2 diabetes in adults using mealtime insulin who have not achieved glucose control. Still marketed †
European Union	Never authorised; a marketing application was not pursued
United Kingdom	Not licensed
Australia	Not approved
South Africa	Not registered †
Sport	Not prohibited by WADA

8Open questions

Whether amylin's modest weight effect in humans was limited by pramlintide's short and dosing burden rather than the pathway itself — the longer-acting analogues are the test.
Cardiovascular safety and benefit — never studied in an outcome trial.
Whether the amylin–leptin synergy can be revisited safely.

9References

1Whitehouse F et al. (2002). A randomized study and open-label extension evaluating the long-term efficacy of pramlintide as an adjunct to insulin therapy in type 1 diabetes. Diabetes Care. PubMed
2Hollander PA et al. (2003). Pramlintide as an adjunct to insulin therapy improves long-term glycemic and weight control in patients with type 2 diabetes: a 1-year randomized controlled trial. Diabetes Care. PubMed · DOI
3Ratner RE et al. (2004). Amylin replacement with pramlintide as an adjunct to insulin therapy improves long-term glycaemic and weight control in type 1 diabetes mellitus: a 1-year, randomized controlled trial. Diabet Med. PubMed · DOI
4Aronne L et al. (2007). Progressive reduction in body weight after treatment with the amylin analog pramlintide in obese subjects: a phase 2, randomized, placebo-controlled, dose-escalation study. J Clin Endocrinol Metab. PubMed · DOI
5Smith SR et al. (2008). Sustained weight loss following 12-month pramlintide treatment as an adjunct to lifestyle intervention in obesity. Diabetes Care. PubMed · DOI
6Ravussin E et al. (2009). Enhanced weight loss with pramlintide/metreleptin: an integrated neurohormonal approach to obesity pharmacotherapy. Obesity. PubMed · DOI
7Roth JD et al. (2008). Leptin responsiveness restored by amylin agonism in diet-induced obesity: evidence from nonclinical and clinical studies. Proc Natl Acad Sci USA. PubMed · DOI
8Hay DL et al. (2015). Amylin: pharmacology, physiology, and clinical potential. Pharmacol Rev. PubMed · DOI
9AstraZeneca. Symlin prescribing information (current label). PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

Not enough data yet. 0 of the 50 members needed have logged this compound for 4+ weeks. We don't show anything below 50, so no one can be identified.

11Page history

26 Oct 2026Profile published — awaiting medical review

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