Pramlintide
Pramlintide (Symlin) — the original approved amylin analog: what it does, and its limits

Class: peptide
INN: Pramlintide
Synonyms: Pramlintide
trade name Symlin (SymlinPen 60 / 120)
pramlintide acetate. INCI: none
Trade names: Symlin
SymlinPen
Function tags: glycaemic (T1D & T2D adjunct)
postprandial glucose/glucagon control
modest weight loss
satiety
Overall evidence grade: A
WADA prohibited: no
Last updated: 2026-07-13

In brief: Pramlintide is the original amylin analog and a long-approved drug (Symlin, FDA 2005) — a synthetic version of amylin, the satiety/glucose hormone co-released with insulin. It works centrally (in the brainstem's area postrema) to suppress post-meal glucagon, slow gastric emptying, and increase satiety, which lowers post-meal glucose spikes and modestly reduces weight. Its honest limits are what define it: HbA1c drops only ~0.3–0.6% and weight loss only ~1–2.3 kg, it must be injected three times daily (at meals, separate from insulin), it's an insulin adjunct (not standalone), it raises hypoglycemia risk when combined with insulin, and nausea is the main side effect. Those limits — modest efficacy, heavy injection burden — are exactly why it was underused and eclipsed by once-weekly GLP-1 drugs. But it proved the amylin concept, and the pathway has now come roaring back through long-acting, once-weekly successors (Cagrilintide, Petrelintide, Eloralintide) and amylin/GLP-1 combos (CagriSema, Amycretin). Pramlintide is the approved-but-modest grandfather of a suddenly-hot class.

## Identity a synthetic **37-amino-acid peptide** analog of **human amylin** (islet amyloid polypeptide, IAPP) — the hormone co-secreted with **insulin** by pancreatic β-cells after meals. Because native human amylin is **highly amyloidogenic** (prone to forming toxic fibrils — it's literally the protein in the amyloid deposits of type-2-diabetic islets), pramlintide was engineered by **substituting three residues from rat amylin** (which doesn't aggregate) while keeping the receptor activity. It carries a disulfide loop (Cys2–Cys7) and an amidated C-terminus. ## Mechanism (as proposed) amylin is co-secreted with insulin after meals; in health the two are **complementary partners** — insulin drives glucose *uptake* into tissues, while amylin controls the *rate glucose appears* in blood. Pramlintide reproduces amylin's three actions, all largely **central** (via **AMY receptors** — calcitonin receptor + RAMP subunits — in the hindbrain **area postrema**): (1) **suppresses post-meal glucagon** (so the liver dumps less glucose), (2) **slows gastric emptying** (glucose enters more gradually), and (3) **promotes satiety** (less food intake). In type 1 diabetes, amylin is **absent alongside insulin**, which is why replacing it adds control that insulin alone can't provide.

Evidence grades by outcome:
outcome: Glycemic control — mealtime-insulin adjunct (T1D & T2D)
grade: A
base: Multiple Phase 3 RCTs → FDA approval 2005; HbA1c reduction ~0.3–0.6% on top of insulin
caveat: Approved and real, but the magnitude is modest; benefit is as an add-on to insulin, not alone; requires 3×/day dosing
outcome: Weight (in diabetes / obesity)
grade: C
base: RCTs + meta-analyses: ~1–2.3 kg loss; separate trials in non-diabetic obesity reduced caloric intake per meal
caveat: Real but small weight effect; never developed/approved as a dedicated obesity drug; dwarfed by GLP-1s and newer amylins
outcome: Postprandial glucose / glucagon suppression
grade: B
base: Consistent across trials (the core mechanism)
caveat: Well-demonstrated physiologic effect; this is what it does best
outcome: Cardiometabolic biomarkers (lipids, BP)
grade: C
base: Small studies: modest LDL/triglyceride reductions (T2D/T1D); neutral on blood pressure
caveat: Limited data; secondary effects, not a primary indication
outcome: Safety / tolerability
base: Approval-grade dataset
caveat: Nausea most common (dose-escalated, then settles); increased hypoglycemia risk when used with insulin (a boxed concern — insulin dose must be reduced); injection burden (3×/day, separate from insulin) is the practical dealbreaker

Legal status:
region: INT
status: availability limited
note: availability limited; primarily a US drug.

Cosmetic claims:

Note: The original amylin drug — approved for 20 years, and the honest foil to the amylin revival. Three points define this entry: (1) it is the founding amylin analog and a genuinely FDA-approved drug (Symlin, 2005) — real, marketed, on-label; (2) but it is modest and niche — small weight loss, three-times-daily injections, an insulin adjunct, not a standalone obesity drug — which is exactly why it was underused; (3) it is the direct ancestor of the hot amylin class now reshaping obesity (Cagrilintide #5, Petrelintide, Eloralintide, Amycretin #51). It's the "approved but modest" counterweight to those newer stars.
Status note: pramlintide's status is stable/old; the moving part is the successor class — re-check Cagrilintide/Petrelintide/Eloralintide milestones

Sources:
SYMLIN (pramlintide acetate) FDA label; FDA approval 2005 (adjunct to mealtime insulin, T1D/T2D).
Cooper GJS, et al. Purification and characterization of a peptide from amyloid-rich pancreas of type-2 diabetics (amylin). PNAS. 1987 (discovery).
Reviews of pramlintide in T1D/T2D — modest HbA1c (~0.3–0.6%) + weight (~1–2.3 kg), nausea, hypoglycemia-with-insulin (Dunican; Domecq meta-analysis).
Kruse T, et al. Development of cagrilintide, a long-acting amylin analogue. J Med Chem. 2021 (notes cagrilintide resembles pramlintide) — the bridge to the modern class.
Long-acting amylin-related peptides for obesity and T2D. (2026 review) — pramlintide as the first AMYR agonist, second-generation successors.