Dual-Hormone AID Systems

Introduction to Dual-Hormone AID Systems

A dual-hormone automated insulin delivery (AID) system uses a continuous glucose monitor (CGM), a pump and a dosing algorithm to deliver two hormones instead of one. Insulin lowers blood glucose. Glucagon raises it [1]. The best-known example is the Beta Bionics iLet, and it shows where things stand as of October 2026: the version the FDA cleared in May 2023 delivers insulin only [2]. The FDA's most recent iLet software clearance, in September 2026, still covers insulin dosing for type 1 diabetes [3], while the bihormonal configuration remains in development [13]. Every trial described below enrolled people with type 1 diabetes. For the insulin-only systems, see our article on closed-loop systems.

Background and Rationale

In people without diabetes, the pancreas releases insulin and glucagon in response to glucose, and the two hormones keep each other in check [1]. Type 1 diabetes disrupts both. The glucagon response weakens over time too, which raises the risk of lows for anyone taking insulin [1].

A standard AID system has one way to respond to falling glucose: cut back or stop insulin. Haidar's 2019 review argues that this is often too slow, especially during aerobic exercise, when glucose can drop faster than suspending insulin can bring it back up [1]. Glucagon delivered under the skin raises glucose faster than an insulin pause does. There is a catch. Glucagon works less well when insulin levels are already high [1].

Innovation and Patents

Most published dual-hormone research comes from a few academic groups and two companies. A Boston University and Massachusetts General Hospital team ran the first multicenter home-use trial of a bihormonal "bionic pancreas," published in 2017 [5]. Company researchers co-authored the first human study of the bihormonal iLet [6]. Teams at McGill University and the Institut de recherches cliniques de Montréal [7], and at Oregon Health & Science University [8], have run randomized trials comparing single- and dual-hormone systems. In the Netherlands, Inreda Diabetic tested its own bihormonal system against usual pump therapy [9].

We have not checked patent holdings for these groups, so we don't describe them here.

Manufacturers and Product Lines

• Beta Bionics: The iLet Bionic Pancreas sold in the US is an insulin-only system cleared for people with type 1 diabetes aged 6 and older [2][3]. The company is separately developing a bihormonal iLet that would deliver insulin and glucagon, using a liquid-stable glucagon based on Xeris Pharmaceuticals' formulation technology under a 2024 agreement [4]. Beta Bionics completed a first-in-human feasibility trial of the full system in New Zealand in the fourth quarter of 2025 [10]. In July 2026 it said a second feasibility trial, started in early 2026, showed that both the glucagon's excipients (the inactive ingredients in the formulation) and the dosing algorithm needed changes, which it expected to take less than a year before more feasibility trials [13].

Effectiveness and Technology Comparison

Against conventional pump therapy, dual-hormone systems have done well in short trials. In the 2017 home-use trial, 39 adults spent 11 days on the bihormonal bionic pancreas and 11 days on their usual pump. Mean CGM glucose was lower with the bionic pancreas (7.8 vs 9.0 mmol/L, about 140 vs 162 mg/dL), and time below 3.3 mmol/L (about 60 mg/dL) fell from 1.9% to 0.6% [5]. Nausea scores were slightly higher on the bionic pancreas [5].

The comparison that matters more is against insulin-only AID, and there the picture is mixed. In the 2015 Montreal crossover trial, time in the target range was nearly identical with single-hormone (62%) and dual-hormone (63%) control, though the dual-hormone arm had fewer low-glucose events, 9 against 13 [7]. The Oregon trial was built around exercise. Over four days, dual-hormone control cut time in hypoglycemia from 2.8% to 1.3%, while time in range was similar (72.0% vs 74.3% for single-hormone) [8].

A 2017 meta-analysis found bigger time-in-range gains for dual-hormone systems. The comparisons weren't like for like, though: six of the seven dual-hormone comparisons were against pump therapy with blinded CGM, while 21 of the 22 single-hormone comparisons were against sensor-augmented pumps [11]. The first human study of the bihormonal iLet was a 10-person pilot with one week in each configuration, and its authors called for much larger and longer pivotal trials [6].

The control side works much like single-hormone AID. The cleared iLet software, for example, responds to a new CGM signal every five minutes [2]. Haidar's review sums up the short-term evidence this way: glucagon reduced daytime lows, especially during exercise, but insulin-only systems seemed enough to prevent lows overnight [1].

Pitfalls, Warnings, and Issues

A second hormone brings a second set of hardware problems. Haidar's review lists a dual-chamber pump, two infusion sites, extra drug handling and more training, and notes that two sites with frequent rotation could be especially hard for young children [1].

Glucagon itself is the larger obstacle. Standard glucagon isn't stable as a liquid, so it isn't suited to continuous pump use [1][12]. Stable versions exist in research settings. The 2021 bihormonal iLet pilot used dasiglucagon, a chemically stable glucagon analog, from a single prefilled cartridge for seven days [6]. Beta Bionics is now working with Xeris on a liquid-stable formulation for its bihormonal pump [4].

Long-term safety is still open. Haidar's review notes that the safety of years of low-dose glucagon hasn't been established and that the FDA will require it before approving any dual-hormone system [1]. Cost is another unknown, because users would need a second drug and the supplies to deliver it [1].

Conclusion

Glucagon gives an AID system a faster answer to falling glucose than stopping insulin does, and short trials show fewer lows, especially around exercise [1][8]. As of the 2019 review, whether that adds up to better A1C or fewer severe lows over the long run was unknown [1]. In February 2026, Beta Bionics said it planned another early feasibility trial in the first half of 2026, followed by a larger feasibility trial meant to prepare for a pivotal study [10]. Whether joining a dual-hormone trial makes sense for you is a decision for your care team.