Co-formulated insulin + pramlintide (single-reservoir)

Type 1 diabetes destroys the cells that make two mealtime hormones, not one: insulin and amylin. Today's therapy replaces only insulin. Amylin's job is to keep the post-meal glucose spike under control — it slows how fast the stomach empties and switches off glucagon (the hormone that raises glucose), so sugar arrives more gently after eating.¹ An amylin analog called pramlintide is approved and on the market, but by 2012 only about 1.5% of people who could benefit were using it — because it has to be a separate injection at every meal, on top of insulin.²

This project, from Eric Appel's lab at Stanford, asks: what if both hormones lived in one reservoir? The obstacle is chemistry. Pramlintide is formulated at acidic pH (~4) while rapid insulins sit near neutral pH (~7), and amylin readily clumps into inactive, immune-provoking fibers — so naively mixing the two is unstable.¹ The team coats both proteins with an amphiphilic copolymer excipient (nicknamed MoNi) that parks itself at the air–water interface and blocks the clumping that starts aggregation.¹ The result is a single co-formulation of monomeric insulin lispro plus pramlintide that stayed stable for 16.2 hours under harsh stressed-aging conditions, versus 8.2 hours for commercial Humalog.¹

The second trick is timing. Injected separately, insulin and pramlintide peak at different times, so they don't work together the way the healthy pancreas co-secretes them. By stripping the zinc from lispro to keep it as fast-absorbing single molecules, the co-formulation pushed insulin–pramlintide overlap to ~75%, versus ~47% for separate injections.¹ In diabetic rats, a simulated meal showed the co-formulation controlled the glucose spike while dropping less below baseline than insulin alone or separate shots — hinting at smoother control with less risk of a post-meal low.¹ An earlier version of this work, stabilized with a cucurbituril-PEG excipient, stayed stable over 100 hours and improved glucagon suppression in diabetic pigs.³

How the "second hormone" defends lows here is different from a glucagon system. Glucagon actively pushes glucose up; amylin instead prevents the overshoot in the first place — flattening the spike so less insulin is stacked and there's less rebound low. That also sidesteps the hardest problem in glucagon-based bihormonal pumps: keeping glucagon stable in solution.¹

Device burden is the headline advantage. Two-hormone glucagon pumps need two cartridges, two pump mechanisms, and two infusion sites. A single-reservoir insulin+amylin product would slot into ordinary pumps and closed-loop systems with no extra hardware — which is exactly why the authors frame it as an enabler for fully-closed "artificial pancreas" systems that need no meal announcements.¹ Notably, a separate Canadian trial already showed a two-pump insulin+pramlintide closed loop with no meal entry reached ~74% time-in-range and roughly halved the share of participants having a low — proving the dual-hormone concept, just with impractical hardware.⁴

Maturity and access: this is early-stage research — diabetic-rat efficacy and formulation chemistry only, no human studies, and the new excipient still needs full safety testing.¹ It is not available anywhere and carries no approval.

What's coming: Because both drugs are individually approved, the main hurdle is proving the excipient is safe in people.² Breakthrough T1D (formerly JDRF) is funding the translation — a roughly $795,000 award running to December 2026 covering pig pharmacokinetics and 28-day rat safety/histopathology studies — explicitly aimed at subcutaneous injection and integration into infusion pumps and closed-loop systems.⁵ If safety clears, first-in-human trials of a single-reservoir dual-hormone product would be the next milestone.

References

1. Maikawa CL, Chen PC, Vuong ET, et al. Ultra-Fast Insulin–Pramlintide Co-Formulation for Improved Glucose Management in Diabetic Rats. Advanced Science (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC8564421/ ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷ ↩⁸ ↩⁹

2. Konno A, et al. (reported in) Stanford/GEN coverage of the Appel lab co-formulation — pramlintide adoption ~1.5% and path to human trials. Genetic Engineering & Biotechnology News (2021). https://www.genengnews.com/topics/drug-discovery/insulin-and-amylin-combined-as-a-potential-new-therapy-for-diabetes/ ↩ ↩²

3. 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). https://doi.org/10.1038/s41551-020-0555-4 ↩

4. 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). https://doi.org/10.1016/S2589-7500%2821%2900139-4 ↩

5. Breakthrough T1D. Ultrafast Insulin-Pramlintide Co-formulations (Eric Appel, Stanford University) — grant summary, $795,000, Sept 2022–Dec 2026. https://www.breakthrought1d.org/grants/united-states/california/ultrafast-insulin-pramlintide-co-formulations/ ↩