Pramlintide

also known as: Symlin, AC137

The FDA-approved amylin analog (Symlin, 2005) — taken at mealtimes alongside insulin in T1D and T2D. The pharmacological proof-of-concept for amylin agonism that petrelintide and cagrilintide are now building on.

A synthetic analog of the β-cell peptide hormone amylin, engineered with three proline substitutions at positions 25, 28, and 29 to prevent the fibril formation that plagues native human amylin; co-secreted physiologically with insulin and acting to suppress glucagon, slow gastric emptying, and promote satiety — properties that have motivated the newer long-acting amylin analogs cagrilintide (CagriSema) and petrelintide.

Mechanism of action

Binds the amylin receptor (a heterodimer of calcitonin receptor and a RAMP protein). Slows gastric emptying, suppresses post-prandial glucagon, and promotes satiety via area postrema signaling. The glucagon suppression and delayed glucose absorption blunt post-meal hyperglycemia, while the satiety effect produces modest weight loss in insulin-dependent patients who historically gain weight on insulin intensification.

Primary uses

Type 1 diabetes mellitus (mealtime insulin adjunct)
Type 2 diabetes mellitus (mealtime insulin adjunct)

Typical dosing

15–120 mcg before each major meal (subcutaneous)

T1D: start 15 mcg, titrate to 30–60 mcg. T2D: start 60 mcg, titrate to 120 mcg. Insulin dose is reduced 50% at initiation to prevent hypoglycemia.

Regulatory status

FDA-approved as Symlin (2005) for type 1 and type 2 diabetes as an insulin adjunct. Carries a boxed warning for severe insulin-induced hypoglycemia. Originally developed by Amylin Pharmaceuticals; rights now with AstraZeneca.

References

[fda-pi] Symlin (pramlintide acetate) Prescribing Information. AstraZeneca.
[pubmed] Ratner RE, et al. "Adjunctive therapy with the amylin analogue pramlintide leads to a combined improvement in glycemic and weight control in insulin-treated subjects with type 2 diabetes." Diabetes Technol Ther, 2002;4:51-61.

Related peptides

Petrelintide

Zealand Pharma's amylin monotherapy — ZUPREME-1 Phase 2b hit its endpoints in March 2026 with up to 10.7% weight loss at 42 weeks and "placebo-like" GI tolerability. Roche-partnered since 2025; Phase 3 planned for late 2026.

CagriSema

Novo Nordisk's next-generation obesity injection — NDA filed December 2025, FDA review expected 2026. If approved, it would be the first GLP-1 + amylin fixed-dose combination and a direct competitive response to tirzepatide.

Semaglutide

A once-weekly GLP-1 receptor agonist FDA-approved for type 2 diabetes and chronic weight management.

Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.