Patch Pumps for Insulin

Abstract

Newly developed patch pumps are starting to occupy a noticeable fraction of the insulin delivery market. New entrants, using novel technologies, promise accurate, flexible insulin delivery at lower costs. In the section, we review the currently available devices, discuss some of the devices on the horizon, and speculate about some fascinating new approaches. In this first article, we provide an overview of the simplified devices—V-Go, PAQ, and One Touch Via—and of the more complex devices—Omnipod, Cellnovo, JewelPump, Solo, SFC Fluidics pump, Libertas, Medtronic pump, and EOPatch. We also discuss controllers, smartphones, and cybersecurity.

With more than 30 million people having diabetes in the United States and about 8 million using insulin, the devices for delivering the drug have assumed increased importance.¹ Although most patients use insulin pens or syringes, a substantial proportion of people with type 1 diabetes and a sizable minority of patients with type 2 diabetes have chosen to use an insulin pump.^2,3 For patients with type 1 diabetes, insulin pumps are complex, expensive devices that provide a range of delivery functions not otherwise available. For patients with type 2 diabetes, the range of functions and the complexity are often unneeded and unwanted.⁴

Over the past few years, a new type of insulin pump has been developed. Called patch pumps, these devices are generally smaller than traditional pumps, attach directly to the skin, and usually have a cannula that goes directly from the device to the skin with no tubing. They can deliver basal insulin, bolus insulin, or both.⁵ The most complex of these devices is appropriate for patients with type 1 diabetes but some of the devices are considerably simplified for patients with type 2 diabetes. Most of the patch pumps have some disposable components and some are completely disposable. Patch pumps are used by about 5% of people who use insulin pumps or about 25,000 people worldwide, most using the Omnipod by Insulet. None of these devices are prefilled, and all must be filled by the user. Some are promising to use cartridges of insulin in the future.

In this special section, I start by describing many of the devices. Following, we will have articles on marketed devices, potential devices, and some futuristic approaches.^6-8

Categories of Patch Pumps

Patch pumps can be categorized as simplified or full-featured devices and as mechanical or electromechanical devices, but these distinctions overlap.

Simplified Devices

These are generally mechanical and fully disposable. The known devices are shown in Table 1. The V-Go is the only device currently available in the United States and Europe. It is a small, plastic device into which the patient loads insulin. It is usually replaced daily. The PAQ is a multiday device, has a CE mark, and is available in Europe. The Via by Johnson and Johnson provides only boluses and has FDA clearance but has not yet been launched.

Table 1.

Simplified Mechanical Patch Pumps.

V-Go by Valeritas (US and Europe)

PAQ by CeQur (Europe only)

OneTouch Via by JNJ (not yet available)

The simplified devices are primarily insulin pen replacements. They have no upfront cost and a low price and are fully disposable. For example, the V-Go is slightly more than $10/day, or $340/month. They have no remote controller. The basal component, if available, is a fixed value that cannot be changed by the user. To change bolus rates you must use a different model. Boluses are given by pressing one or two buttons to deliver a fixed amount, usually 2 units of insulin. All of the pumps in this category have integrated cannula and have automated insertion mechanisms.

Full-Featured Devices

These are very flexible devices fully capable of the most complex regimens of an insulin-using patient. They are generally electromechanical, a mechanical pump with an electronic controller, and are usually at least partially disposable. In some, the electronics are saved, whereas the pump and reservoir are disposable. The known devices are shown in Table 2, but most are not available yet. The Omnipod is in its smaller third version and is available in the United States and Europe. The Cellnovo is approved and sold in Europe. The remainder of the devices are still under development.

Table 2.

Full-Featured Electromechanical Patch Pumps.

Omnipod by Insulet

Cellnovo

JewelPump by Debiotech

Solo by Roche

SFC Fluidics PatchPump

Libertas by BD

Medtronic PatchPump

EOPatch by EOFlow

These are all full-featured pumps, with variable basal rate(s) and individually controllable bolus amounts. They may have fewer choices about the shape of bolus delivery. Their advantages are smaller size and lower up-front costs. Over the 4-year lifetime of a standard pump, the overall costs of a complex patch pump and a standard pump are similar. In this category, most pumps have integrated cannula and automated insertion. The Cellnovo and the Roche Solo, however, have short tubing that is detachable.

Specific Simple Patch Pumps

V-Go by Valeritas

The V-Go has been available for several years and is used primarily by patients with type 2 diabetes. The patient can use the device for only a single day. The overall size is inches, and it weighs less than 2 ounces, filled with insulin (Figure 1). It comes in 3 models, each with a different basal rate: 20, 30, or 40 units/day.⁹ To deliver a bolus, the patient presses a lock release, then a delivery button, delivering 2 units. The lock release must be pressed before each 2 unit delivery. The device is capable of delivering a 2 unit dose 18 times per day. Thus, the maximum daily dose is 76 U (basal of 40 bolus maximum of 36). It is approved for both U100 lispro and U100 aspart insulins. Although lispro is available at U200 (allowing a 152 Unit total daily dose), the V-Go does not appear to be approved for use with this insulin, and the more concentrated insulin is available only in a pen. The V-Go is covered by many insurance plans including several Medicare part D plans

Figure 1.

The V-Go by Valeritas.

The mechanism is shown on Figure 2. There is a needle inserter, which inserts a 4.6 mm 30 ga metal needle into the subcutaneous tissue (Figure 2A). For the basal insulin. a spring pushes on a syringe-like device containing silicone oil. A flow restrictor determines the actual basal rate (B), pushing the plunger of a syringe containing insulin. For a bolus, after releasing the lock, the patient pushes on the delivery button (C) to compress the cylinder of silicone oil to deliver 2 units of insulin. Although there is a clear area over the syringe to see how much insulin remains, there is no “counter” to remind the patient of how much insulin s/he has taken.

Figure 2.

Technical details of V-Go.

PAQ by CeQur

There is an article on this device in this section.⁶ The PAQ has a CE mark and is sold in Europe. It has a disposable insulin containing portion and a small reusable electronic portion (Figure 3). It is a 3-day device that can hold up to 330 units of U100 insulin and comes in models that provide basal rates of 16, 20, 24, 32, 40, 50, or 60U per 24-hour period. Pressing the delivery button provides a bolus of 2 units, and the button is recessed to prevent accidental pressing. There is no insulin counter, but there is a dose count card and notification to replace the unit. The unit is about 3 inches across.

Figure 3.

The PAQ by CeQur. The reusable part is shown in light gray.

Placing insulin through the port found on the underside of the device stretches a balloon and serves as the power for the device. The basal rate is controlled by a flow restrictor.

Via by Johnson and Johnson

This device initially developed by Calibra has FDA clearance but has never been marketed (Figure 4). It is designed as an insulin pen replacement, providing boluses but no basal insulin. The 3-day device can hold up to 200 units of U100 insulin. Pressing the buttons on both sides of the device delivers 1 or 2 units of insulin, depending on the model. There is no insulin delivery counter. The device will lock up if clogged.

Figure 4.

The Via by JNJ.

Specific Full-Featured Device: Omnipod by Insulet

Versions of the Omnipod have been on the market for over 10 years. The current Omnipod is the second iteration (Figure 5), and there is a third iteration currently being evaluated by the FDA (see separate article later in this issue). It is a fully capable insulin pump with preset basal rates and manual boluses. The Omnipod is about 2 inches long, 1.5 inches wide, and 0.6 inches thick (Figure 5).

Figure 5.

Omnipod by Insulet.

The Omnipod can hold 200 units of U100 insulin and can be used for 3 days. The Omnipod can be programmed with up to 24 basal rates in a single program and can have up to 6 programs. Boluses may be adjusted in intervals of 0.05U and may be programmed as a standard wave, an extended wave (timing controlled by user) or a dual wave (both standard and extended). The Omnipod itself has no controls but is programmed by a handheld controller. The controller has a built in blood glucose meter and a bolus calculator.

The Omnipod uses a Nitinol wire, a shape memory alloy, to drive the pump. The wire has two configurations, one when cold and another when heated. On top, in the cartoon in Figure 6, is the mechanism in the cold state. As seen in bottom, when the switch is closed (A) the battery (B) heats the wire (Red, C) and changes its shape. In the new shape, the heated wire pulls a control lever (D) that moves a ratchet (E) that drives a plunger(F) in an insulin reservoir (G) and delivers insulin. The wire then cools and returns to its original shape and the process repeats.

Figure 6.

Cartoon of how the Omnipod works.

Cellnovo

The Cellnovo system, sold in Europe, consists of a small patch pump, about 2 × 1.5 × 0.6 inches, that adheres to the skin with a short length of tubing that ends in a cannula (Figure 7). Because the cannula is not part of the pump, a variety of cannulas are available. The pump holds a 150-unit disposable cartridge, so some patients will be able to use it for up to 3 days, but many can only use it for 2. The pump itself is reusable and can be detached from the cannula and removed for a shower or to go swimming. The pump has no buttons on it and is controlled by a “smartphone-like” controller. The controller holds the basal pattern (up to 20 patterns), a blood glucose monitor, a food application, a bolus calculator, and historical data on insulin doses, food choices, and blood glucose. Operating temperature is limited to 98.6°F, presumably because of the wax engine (see below).

Figure 7.

The Cellnovo pump and controller.

The pump is cable of delivering 0.05 units, so the available basal rates are 0.05-5U/hr and boluses can be 0.05-30 units. The wax engine is slow (1 U/min), so bolus delivery takes longer than other pumps and require a greater interval between bolusing and eating, but patterns of immediate, extended, dual, and multi phases are available. It requires about a unit of insulin to detect an occlusion, so about 60-90 minutes at a basal rate of 0.8U/hr.¹⁰

The mechanism of pumping, the “Wax Engine” is unique. A cartoon of the basics is shown in Figure 8. To deliver insulin, a block of wax (A) is heated by a diode (B), expanding and pushing on a plunger (C). The plunger sits in a syringe of insulin (D) and pushes the insulin out the outlet valve (E) and to the patient (F). The hotter the wax, the greater the expansion and the larger the bolus of insulin. After the dose, the wax cools, shrinking and pulling the plunger back. When this happens, the outlet valve (E) closes and inlet valve (G) opens and insulin is drawn in from the cartridge (H).

Figure 8.

Cartoon of how the Cellnovo pump works.

JewelPump by Debiotech

Debiotech demonstrated the JewelPump at the American Diabetes Association Scientific Sessions in 2010. The pump is still advertised on their website, claiming it is currently in clinical trials. Currently, the JewelPump has neither FDA nor EU clearance. Nevertheless, it has a set of interesting features, making it worth discussing (Figure 9).

Figure 9.

The JewelPump by Debiotech.

The pump uses a piezoelectric crystal to propel the insulin (see Figure 10). It is 2.6 × 1.6 × 0.6 inches and holds 500 units of insulin. The disposable portion, shown on the left in Figure 9 consists of a pump with reservoir and a detachable needle (clear).

Figure 10.

How the JewelPump works. Red is the structural elements. The piezo-electric crystal is purple, the pumping membrane orange, and the valves blue.

Piezoelectric crystals are widely used in electronics. They serve as speakers for many devices. A flat crystal will bend in one direction when a current is placed across it. If the current is reversed by reversing the polarity, it bends in the other direction. The principle of using this bending to pump a fluid like insulin is shown in the top of Figure 10.

Early pumps based on piezoelectric crystals were notoriously inaccurate. The pumped volume varied from stroke to stroke. To gain accuracy these early devices had to place complex fluid measuring devices into the pump and set the pump based on the actual fluid pumped rather than the number of strokes pumped. Debiotech has developed a piezoelectric crystal pump that has stroke that appears to be accurate enough to not require a delivery rate measuring device.

In Figure 10A a negative current is run through the piezo, causing it to bend downward and displacing all of the fluid in the pumping chamber. In Figure 10B the current is stopped, causing the piezo to flatten and draw insulin into the chamber. Note the inlet valve is open and the outlet valve is closed. A positive current (Figure 10C) is applied and the piezo bends upward, drawing still more insulin into the chamber. The current is stopped again (Figure 10D) and the piezo springs back to flat, discharging insulin out the open outlet valve, as the inlet valve closes. Finally, a negative current is reapplied (Figure 10A) and the remainder of the insulin is discharged. The lower picture shows the full size of the crystal and valves.

Solo Pump by Roche

The Solo Pump was developed by Medingo and received FDA clearance in 2009. The pump was purchased by Roche in 2010 but never released to the market. There has never been a public announcement of the rationale.

The pump is 2.4 × 1.5 × 0.5 inches and consists of 2 parts, a disposable reservoir and a reusable pumping mechanism. There are buttons on the pump to control it (Figure 11) and it has detachable tubing.

Figure 11.

The Solo Pump by Roche.

Other Pumps

There is generally much less information available about the remainder of the pumps.

The SFC Fluidics pump is described in one of the articles in this section. The pump uses the electrically generated increase in osmolality to move water osmotically. The water pushes on a pumping chamber to pump the insulin.

In Figure 12, an electrical current in the right chamber (brown) alters a large molecule, (circles) generating smaller, more osmotic molecules (white triangles). This causes an osmotic flow of solvent from the left chamber (orange) through the semipermeable, rigid interchamber membrane to the right chamber. The right chamber then bulges its impermeable flexible membrane (blue) into the pumping chamber (gray) and pumps insulin. A second pumping chamber may be added at the left for a second hormone.

Figure 12.

How the SFC Fluidics pump works.

Becton Dickinson has been showing pictures of its new wearable autoinjector. It can deliver a number of medications including insulin. Details are sketchy, but the pump will have its own cartridge, can deliver basal and bolus doses and will not be available until 2019.

Medtronic has been promising a patch pump for years. No designs have been seen and a delivery date has not been announced.

EOFlow has been describing its EOPatch patch pump. Externally, it looks a lot like the Omnipod, but slightly smaller. JDRF is funding clinical trials of the pump.

Controllers

All of the complex pumps utilize controllers. Many have no controls on the pump itself and others have very limited on-pump controllers. The controllers look a lot like smartphones, and one device the JewelPump was initially designed to be controlled by a smartphone. Most patients already have a smartphone and many already use one to monitor their continuous glucose monitoring system. Why not have it control the pump?

Regulatory authorities around the world are worried that the smartphones may be cybersecurity targets and that a hacker could alter the programming of a smartphone to trick the patient into overdosing their insulin or a hacker could potentially take over a smartphone and deliver a lethal dose of insulin to a patient.

Securing smartphones is difficult. There are at least 3 platforms (iOS, Android, and Windows), each with multiple versions and iterations, and all are then housed on literally hundreds of different phones from dozens of manufacturers around the world.

To help with this problem, the Diabetes Technology Society, the organizer of this journal, set up a working group in 2016 that developed a standard for cybersecurity of diabetes devices called DTSec.¹¹ In 2017 they set up an additional committee and developed DTmoST,¹² a description of how to ensure that a smartphone could be safely used to control a device such as an insulin pump.

Advantages and Disadvantages

Patch pumps have two very different groups of potential users. The largest group would be patients with type 2 diabetes on simple insulin regimens. They may be on basal-bolus therapy but would not be using multiple basal insulin rates and would not need an additional insulin push for the dawn phenomenon. They could use the simple devices like the V-Go or the PAQ. These devices are small, light, connect directly to the patient without tubing and are relatively inexpensive. They suffer from three problems: (1) They have a limited number of fixed basal doses. To changes the basal rate you need to change to a different model. (2) They don’t keep track of how much insulin you have taken. Since you need to press one or two buttons for each two units, you may be pressing a lot of buttons. If you are interrupted, you may not remember how much insulin you have already given yourself. (3) The devices cannot be taken off. If you take them off for a shower or to go swimming, you need to put on a fresh device. A summary of different pump features can be found in Table 3.

Table 3.

Summary of Pump Features.

Pump	Availability	Type	Size (inches)	Usage (days)	Basal (U/hr)	Bolus (U)	Bolus pattern	Controller
V-Go	US/Europe	Simplified	2.4 × 1.3 × 0.5	1	0.8, 1.3, 1.7	2-36	P	None
PAQ	Europe	Simplified	~2.5 × 3 × 0.5	3	0.7, 0.8, 1, 1.4, 1.7, 2.1, 2.5	Remaining	P	None
Omnipod	Worldwide	Full feature	2 × 1.5 × 0.6	2-3	0.05-10	0.05-	P, S, D	Proprietary
Cellnovo	Europe	Full feature	2 × 1.5 × 0.6	2	0.05-5	0.05-30	P, S, D, M	Proprietary
JewelPump	Coming	Full feature		7	0.02-	0.02	NA	Smartphone (?)
Solo	Coming	Full feature	2.4 × 1.5 × 0.6	2-3	0.1-30	0.1-30	P, S, D, M	Proprietary

D, dual wave (P+S); M, multiwave (complex pattern of P+S or graphically set); P, immediate pulse wave; S, square wave over previously set time.

All patients with type 1 diabetes and some with type 2 diabetes will need the more complex patch pumps. These have the advantage of flexibility in basal and bolus doses; some can be removed without removing the needle for a shower or swimming, and they all keep track of doses. Most have needles that go directly from the device to the patient, eliminating kinking and determining a blockage quicker. However, most do not have controls on the pump, and the loss or failure of a controller makes them unusable. Most are also expensive, and if the needle clogs the entire device must be changed.

Patch pumps are an exciting area that is destined for significant innovation over the next few years.