Insulin + pramlintide (amylin) closed loop

Most artificial-pancreas work uses one hormone — insulin — to push glucose down. This approach adds a second hormone, pramlintide, a lab-made copy of amylin, which a healthy pancreas releases from the same cells as insulin at every meal and which people with T1D lose almost entirely.¹ Pramlintide does not raise glucose the way glucagon does; instead it slows stomach emptying, blunts the after-meal glucagon surge, and increases fullness, so the meal-time spike is smaller and slower.¹ In a closed loop, that smoother rise is easier for the insulin algorithm to chase — the goal is steadier glucose with less reliance on perfect carb counting.²

What the trials show. A McGill randomized crossover trial found that a rapid-insulin-plus-pramlintide artificial pancreas raised time-in-range from 74% to 84% versus insulin alone, driven mostly by better daytime control (63% to 78%), without any increase in hypoglycemia.³ A follow-on McGill trial showed the pramlintide system could replace carb counting with a simple meal announcement while keeping glucose control as good as carb-counting alone.⁴⁵ A fully-closed-loop version with no meal input held a high time-in-range and produced fewer low-glucose events than the insulin-only loop (one third vs over half of participants had a low).⁶ The recurring cost is gut side effects — mild-to-moderate nausea or bloating in a meaningful minority.³⁴

Glucagon vs amylin. This is the key contrast with glucagon-based dual-hormone systems. Glucagon actively raises glucose, giving the loop a brake against lows, but it is chemically unstable in a pump. Pramlintide doesn't defend against lows directly — it makes the whole post-meal curve gentler, so the loop has less to fight.¹

The formulation challenge. Pramlintide and insulin cannot share a reservoir: pramlintide is formulated at an acidic pH, insulin near neutral, and the two aggregate and lose activity when mixed, which is why Symlin must be a separate injection.⁷⁸ Today's research systems therefore use two pumps or two pods — one for each hormone.² A major engineering effort aims to fix this: Stanford researchers built a stable insulin-pramlintide co-formulation that resisted aggregation for over 16 hours,⁹ and the company Adocia has tested a fixed co-formulation (ADO09) in people, improving post-meal glucose and time-in-range with less mealtime insulin.¹⁰ A single stable mixture is what would let this run from one pump.

Maturity and access. The drug itself is mature — pramlintide was FDA-approved as Symlin in 2005 as a subcutaneous adjunct to mealtime insulin in T1D, and carries a boxed warning for severe insulin-induced hypoglycemia.¹¹ But the automated closed-loop co-delivery is investigational: there is no approved insulin-pramlintide artificial pancreas, and it is reachable today only through studies (for example OHSU's "iPancreas" program, testing insulin-plus-pramlintide on an Omnipod platform with a Dexcom sensor).¹²

What's coming. Two threads to watch. First, fully-automated, no-carb-counting systems: McGill's registered trial tests insulin-plus-pramlintide at fixed 8 and 10 µg-per-unit ratios with meal-forecasting algorithms,¹³ and OHSU is pairing pramlintide delivery with software that predicts when a meal has started.¹² Second, the single-reservoir co-formulation — if a pump-stable insulin-pramlintide mixture reaches the clinic, this could shrink from a two-pump rig into something close to the footprint of a standard automated insulin delivery system, making the amylin route a realistic everyday option rather than a research-only setup.

References

1. Pullman J, Darsow T, Frias JP. Pramlintide in the management of insulin-using patients with type 2 and type 1 diabetes. Vascular Health and Risk Management (2006). According to PubMed, PMID 17326327. https://doi.org/10.2147/vhrm.2006.2.3.203 ↩ ↩² ↩³

2. Haidar A, Tsoukas MA, Bernier-Twardy S, et al. A Novel Dual-Hormone Insulin-and-Pramlintide Artificial Pancreas for Type 1 Diabetes: A Randomized Controlled Crossover Trial. Diabetes Care (2020). According to PubMed, PMID 31974099. https://doi.org/10.2337/dc19-1922 ↩ ↩²

3. Haidar A, Tsoukas MA, Bernier-Twardy S, et al. A Novel Dual-Hormone Insulin-and-Pramlintide Artificial Pancreas for Type 1 Diabetes: A Randomized Controlled Crossover Trial. Diabetes Care (2020). According to PubMed, PMID 31974099. https://doi.org/10.2337/dc19-1922 ↩ ↩²

4. Tsoukas MA, Cohen E, Legault L, et al. Alleviating carbohydrate counting with a FiASP-plus-pramlintide closed-loop delivery system (artificial pancreas): Feasibility and pilot studies. Diabetes, Obesity & Metabolism (2021). According to PubMed, PMID 34047449. https://doi.org/10.1111/dom.14447 ↩ ↩²

5. Cohen E, Tsoukas MA, Legault L, et al. Simple meal announcements and pramlintide delivery versus carbohydrate counting in type 1 diabetes with automated fast-acting insulin aspart delivery: a randomised crossover trial in Montreal, Canada. The Lancet Digital Health (2024). According to PubMed, PMID 38906614. https://doi.org/10.1016/S2589-7500(24)00092-X ↩

6. Tsoukas MA, Majdpour D, Yale JF, et al. A fully artificial pancreas versus a hybrid artificial pancreas for type 1 diabetes: a single-centre, open-label, randomised controlled, crossover, non-inferiority trial. The Lancet Digital Health (2021). According to PubMed, PMID 34580055. https://doi.org/10.1016/S2589-7500(21)00139-4 ↩

7. Maikawa CL, Smith AAA, Zou L, et al. A co-formulation of supramolecularly stabilized insulin and pramlintide enhances mealtime glucagon suppression in diabetic pigs. Nature Biomedical Engineering (2020). According to PubMed, PMID 32393892. https://doi.org/10.1038/s41551-020-0555-4 ↩

8. Maikawa CL, Smith AAA, Zou L, et al. A co-formulation of supramolecularly stabilized insulin and pramlintide enhances mealtime glucagon suppression in diabetic pigs. Nature Biomedical Engineering (2020). According to PubMed, PMID 32393892. https://doi.org/10.1038/s41551-020-0555-4 ↩

9. Maikawa CL, Smith AAA, Zou L, et al. A co-formulation of supramolecularly stabilized insulin and pramlintide enhances mealtime glucagon suppression in diabetic pigs. Nature Biomedical Engineering (2020). According to PubMed, PMID 32393892. https://doi.org/10.1038/s41551-020-0555-4 ↩

10. Andersen G, Eloy R, Famulla S, et al. A co-formulation of pramlintide and insulin A21G (ADO09) improves postprandial glucose and short-term control of mean glucose, time in range, and body weight versus insulin aspart in adults with type 1 diabetes. Diabetes, Obesity & Metabolism (2023). According to PubMed, PMID 36633505. https://doi.org/10.1111/dom.14972 ↩

11. U.S. Food and Drug Administration. SYMLIN (pramlintide acetate) injection — full prescribing information, including boxed warning for severe insulin-induced hypoglycemia (NDA 021332, original approval 2005). FDA Drugs@FDA (2005). https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021332lbl.pdf ↩

12. Oregon Health & Science University / Breakthrough T1D Pacific Northwest. T1D Insulin and Pramlintide Dual-Delivery Study at OHSU ("iPancreas"): a closed loop delivering insulin and pramlintide via Omnipod pods with a Dexcom CGM, paired with a meal-forecasting algorithm. Breakthrough T1D (16 September 2024). https://www.breakthrought1d.org/pacificnorthwest/2024/09/16/t1d-insulin-and-pramlintide-dual-delivery-study-at-ohsu/ ↩ ↩²

13. Odabassian M, Tsoukas MA, Cohen E, et al. A Pilot Outpatient Assessment of a Fully Closed-Loop Insulin and Pramlintide System. Journal of Diabetes Science and Technology (2025). According to PubMed, PMID 41174925. https://doi.org/10.1177/19322968251371046 ↩