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INSULIN PUMPS

An external insulin pump delivers insulin via a cannula inserted just under the skin. The set basal rate on insulin pumps represents the amount of insulin delivered continuously for normal daily functions, without the consideration of food intake. The rate is determined by the professional provider. Bolus doses represent the additional insulin delivered on demand to support food intake or to correct an elevated blood glucose (BG) level. Insulin pumps have bolus calculators that assist in calculating the appropriate bolus amount based on settings that are determined by the professional provider.

A disposable external ambulatory insulin delivery system (also known as patch pump or tubeless insulin pump) is generally smaller than a conventional insulin pump, attaches directly to the skin by means of an adhesive layer, and has a cannula that goes directly from the device to the skin with no tubing. This type of system usually requires the user to fill the insulin reservoir as only a few systems have the option of using prefilled cartridges. The system can deliver basal insulin, bolus insulin, or both. 

The Omnipod® Insulin Management System, also known as the Omnipod Classic (Insulet Corporation, MA) was approved by the US Food and Drug Administration (FDA) on September 24, 2012, for the subcutaneous delivery of insulin at set and variable rates for the management of diabetes mellitus in individuals requiring insulin. The system features a disposable insulin infusion pump (Pod) and an associated wireless remote controller referred to as the Personal Diabetes Manager (PDM). The pod is a body-wearable insulin pump that affixes to the user on the back of the arm, the lower back or abdomen, the thigh area, or any site that has a layer of fatty tissue available. It is held in place by an adhesive pad and provides up to 3 days of insulin before it is removed and replaced with a new pod. The PDM is a handheld device that controls the pod. The user interfaces with the device system through the PDM, where they control basal and bolus delivery and various insulin program settings and calculations. The PDM has an integrated BG meter and communicates with the pod wirelessly. Insulet Corporation discontinued this system in the United States as of December 31, 2023. Other versions of the Om nipod System exist, such as the Omnipod® DASH and Omnipod® 5 Automated Insulin Delivery (AID) System (Omnipod 5); however, the manufacturer is only making these products available through the retail pharmacy channel with a valid prescription and pharmacy coverage, and not through a durable medical equipment (DME) supplier.  

SENSOR-AUGMENTED INSULIN PUMP THERAPY SYSTEMS
The sensor-augmented insulin pump therapy system combines both an insulin pump and continuous glucose monitoring (CGM) technology into one system. This system has been investigated to determine the effect of the sensor-augmented insulin pump system technology on the hemoglobin A1c (HbA1c) level in an individual with type 1 diabetes, compared to using multiple daily insulin injections.

Bergenstal et al. performed a randomized controlled trial (RCT) involving 420 subjects (STAR 3). The objective of the study was to examine the effects of crossing over from optimized multiple daily injection (MDI) therapy to sensor-augmented pump (SAP) therapy for 6 months, and the effects of 18 months using the SAP system. The STAR 3 eligibility criteria included individuals with type 1 diabetes who were between the ages of 7 and 70 years, who used MDI with a long-acting insulin analogue, whose HbA1c levels were between 7.4% and 9.5%, and who experienced less than two severe hypoglycemic events in the previous year. Individuals in the study were randomly assigned into one of two groups: those who would receive SAP (Paradigm REAL-Time System, Medtronic MiniMed, Inc., Northridge, CA) with insulin aspart and those who would receive optimized MDI therapy using aspart and glargine for 12 months. The individuals had their HbA1c levels obtained during quarterly visits, at 3, 6, 9, and 12 months, after randomization. At 12 months, the continuation phase of the STAR 3 study began, with the individuals from the optimized MDI group switching to SAP therapy for 6 months (the crossover group) and were then compared to those individuals continuing for another 6 months on SAP therapy, for a total of 18 months. The results of the HbA1c levels were initially lower in the continuing SAP group than the crossover group. However, individuals in the crossover group saw a significant decrease in HbA1c from 12 months (8.0 ± 0.1%) to 15 or 18 months (7.6 ± 0.1%; P<0.001). The significant decrease in HbA1c values in the crossover group was seen in both adult (n=141) and pediatric (n=63) individuals. Overall results concluded that the effectiveness of SAP therapy on individuals transitioning from optimized MDI therapy allowed for rapid and safe HbA1c reductions. Glycemic benefits, resulting in a decreased HbA1c when utilizing SAP therapy, persisted for at least 18 months.

LONG-TERM INTERSTITIAL CONTINUOUS GLUCOSE MONITORING SYSTEM (CGMS)

A long-term interstitial CGMS is indicated for use in individuals with diabetes who require insulin and/or need to be monitored for unexplained glycemic fluctuations and hypoglycemic unawareness. Hypoglycemic unawareness is the inability of an individual to notice and recognize symptoms of hypoglycemia while they are experiencing them. Complications of unaddressed hypoglycemia may include diabetic coma, brain damage, and seizures.

Long-term interstitial CGMS devices allow individuals to track glucose levels and detect episodes of high and low blood sugar in real time on an ongoing basis. The device consists of a disposable subcutaneous sensor, an external transmitter, and an external receiver (monitor), which can be a stand-alone device or built into an insulin pump. Sensors are worn as indicated by the device manufacturer in accordance with FDA labeling and are replaced on an ongoing basis.

Depending on the device sensor longevity capability, a long-term CGMS sensor measures interstitial glucose levels for 6 to 14 days. The Eversense® E3 implantable glucose sensor can measure levels for up to 180 days and requires professional insertion. Use of these devices requires the glucose sensor to be implanted subcutaneously, usually in the abdomen, the back of the upper arm, or in an area above the buttocks. The transmitter is connected to the sensor by an adhesive patch, and glucose signals are sent from the sensor to the receiver every 1 to 5 minutes. Interstitial glucose values appear on a liquid crystal display (LCD) screen on the receiver, where they can be read and reviewed by the individual. These data may be stored and downloaded for analysis. CGMS devices also allow for customization of threshold settings, such as alarms, to detect high and low glucose levels.

The FDA has approved several long-term interstitial CGMS devices to assist in analyzing glycemic trends in the ongoing evaluation and management of individuals with diabetes.

For individuals with type 1 diabetes who are willing and able to use the device, and have adequate medical supervision, who receive long-term CGM, the evidence includes RCTs and systematic reviews. Relevant outcomes are symptoms, morbid events, quality of life (QOL), and treatment-related morbidity. RCTs have evaluated both real-time and intermittently scanned CGMs. Long-term CGM resulted in significantly improved glycemic control for adults and children with type 1 diabetes, particularly highly compliant individuals. Two RCTs in individuals who used MDIs and were highly compliant with CGM devices during run-in phases found that CGM was associated with a larger reduction in hemoglobin HbA1c levels than previous studies. One of the two RCTs prespecified hypoglycemia-related outcomes and reported that time spent in hypoglycemia was significantly less in the CGM group. One RCT in pregnant women with type 1 diabetes, which compared real-time CGM with self-monitoring of BG (SMBG), has also reported a difference in change in HbA1c levels, an increased percentage of time in the recommended glucose control target range, a smaller proportion of infants who were large for gestational age, a smaller proportion of infants who had neonatal intensive care admissions lasting more than 24 hours, a smaller proportion of infants who had neonatal hypoglycemia requiring treatment, and reduced total hospital length of stay all favoring CGM. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome. 

For individuals with type 2 diabetes who receive long-term CGM, the evidence includes RCTs. Relevant outcomes are symptoms, morbid events, QOL, and treatment-related morbidity. Three RCTs have evaluated CGM compared to SMBG in individuals with type 2 diabetes on intensive insulin therapy; one using real-time CGM and two using an intermittently scanned device. One RCT evaluated CGM in patients treated with basal insulin. All found either improved glycemic outcomes or no difference between groups with no increase in hypoglycemic events. In the DIAMOND trial, the adjusted difference in mean change in HbA1c level from baseline to 24 weeks was −0.3% (95% CI, −0.5%–0.0%; P=0.022) favoring CGM. The adjusted difference in the proportion of patients with a relative reduction in HbA1c level of 10% or more was 22% (95% CI, 0%–42%; P=0.028) favoring CGM. There were no events of severe hypoglycemia or diabetic ketoacidosis in either group. Yaron et al. (2019) reported higher treatment satisfaction with CGM compared to control (the primary outcome). At 12-month follow-up in one of the trials of the Freestyle Libre device, hypoglycemic events were reduced by 40.8% to 61.7% with a greater relative reduction in the most severe thresholds of hypoglycemia. In the Martens et al. trial of individuals treated with basal insulin without prandial insulin, there was a statistically significantly greater decrease in mean HbA1c in the CGM group (adjusted difference, −0.4%; 95% CI, −0.8% to −0.1%; P=0.02), with one hypoglycemic event in each group. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

According to the FDA, on December 20, 2016, the Dexcom G5 Mobile Continuous Glucose Monitoring (GCM) System received supplemental approval as the first device that can be used as a replacement for finger-stick testing in individuals 2 years of age and older for diabetes treatment decisions. Interpretation of the results of the device should be based on the glucose trends and several sequential readings over time. The product also aids in the detection of episodes of hyperglycemia and hypoglycemia, facilitating both acute and long-term therapy adjustments. Fingersticks are required for calibration, at least once every 12 hours. More frequent calibrations may be required if symptoms do not match readings or when taking medications containing acetaminophen, which can falsely elevate the device's readings.

The Dexcom G6 CGM System was approved by the FDA on October 26, 2018, as a therapeutic CGM system intended to replace fingerstick BG testing in individuals 2 years of age and older for diabetes treatment decisions. The system features a 10-day wear sensor, is factory calibrated with optional user calibration, and can autonomously communicate with digitally connected devices such as an automated insulin dosing system.

The Dexcom G7 CGM System was approved by the FDA on December 7, 2022, and is a real-time CGM device indicated for the management of diabetes in individuals 2 years and older. The system is intended to replace fingerstick BG testing for diabetes treatment decisions. Interpretation of the Dexcom G7 CGM System results should be based on the glucose trends and several sequential sensor readings over time. The system also aids in the detection of episodes of hyperglycemia and hypoglycemia, facilitating both acute and long-term therapy adjustments. It is also intended to autonomously communicate with digitally connected devices, including automated insulin dosing (AID) systems. The Dexcom G7 CGM System can be used alone or in conjunction with these digitally connected medical devices for the purpose of managing diabetes. 

The FreeStyle® Libre 14 Day Flash Glucose Monitoring System (CGM) was approved by the FDA on July 23, 2018, as a therapeutic CGM system, indicated for the management of diabetes in individuals 18 years of age and older. The system requires no user calibration whatsoever (either by finger-stick or manual data entry), because it is factory calibrated. The system also does not require the need for routine fingersticks. The high accuracy of the FreeStyle® Libre system allows for patients to dose insulin based on the results. The system interprets glucose levels through a sensor that is worn on the back of the upper arm for up to 14 days. The sensor wire inserted below the skin's surface on the back of the arm continuously measures and monitors glucose levels. The FreeStyle® Libre system does not have alarms that will automatically alert an individual when a severe low (hypoglycemic) or high (hyperglycemic) glucose event is occurring, unless the sensor is scanned. The goal intended with using the FreeStyle® Libre system is to replace BG testing for diabetic treatment decision-making.

The FreeStyle® Libre 2 Flash Glucose Monitoring System (CGM) was approved by the FDA on June 12, 2020, as a therapeutic CGM system with real-time alarms capability indicated for the management of diabetes in individuals 4 years of age and older. 

The FreeStyle® Libre 3 Continuous Glucose Monitoring System was approved by the FDA on May 26, 2022, as a real-time CGM device with alarms capability indicated for the management of diabetes in individuals 4 years of age and older. It is intended to replace BG testing for diabetes treatment decisions, unless otherwise indicated. The system is also intended to autonomously communicate with digitally connected devices. The system can be used alone or in conjunction with these digitally connected devices where the user manually controls actions for therapy decisions.

CGM IMPLANTABLE GLUCOSE SENSOR

The Eversense® CGM System is implanted in the subcutaneous skin layer and provides continuous glucose measurements over a 40- to 400-mg/dL range. The system provides real-time glucose values, glucose trends, and alerts for hypoglycemia and hyperglycemia and low glucose through a mobile application installed on a compatible mobile device platform. The Eversense® CGM System is a prescription device indicated for use in adults (age 18 and older) with diabetes for up to 90 days. The device was initially approved by the FDA as an adjunctive glucose-monitoring device to complement information obtained from standard home BG-monitoring devices. Expanded approval was granted in June 2019 and Eversense® is now approved as a device to replace fingerstick BG measurements for diabetes treatment decisions. The newest version, the Eversense® E3 CGM System, received FDA approval on February 10, 2022, and is indicated for continually measuring glucose levels in adults (18 years and older) with diabetes for up to 180 days. Prescribing providers are required to participate in insertion and removal training certification.

In a prospective, multicenter trial, Kropff et al. (2017) studied the Eversense (Senseonics Inc.) implantable CGM sensor in 71 participants aged 18 years and older with type 1 and type 2 diabetes. Participants used the CGM system at home and in the clinic. CGM accuracy was assessed during eight in-clinic visits with the mean absolute relative difference (MARD) for venous reference glucose values greater than 4.2 mmol/L as the primary endpoint. Secondary endpoints included Clarke Error Grid Analysis and alarm performance. The primary safety outcome was device-related serious adverse events (SAEs). The MARD value against reference glucose values greater than 4.2 mmol/L was 11.1% (95% CI, 10.5–11.7). Clarke Error Grid Analysis showed 99.2% of samples in the clinically acceptable error zones A and B. Eighty-one percent of hypoglycemic events were detected by the CGM system within 30 minutes. No device-related SAEs occurred during the study. Results indicated the safety and accuracy of this new type of implantable CGM system and supported it as an alternative for transcutaneous CGM.

In a nonrandomized, blinded, prospective, single-arm, multicenter study (PRECISE II), Christiansen et al. (2018) evaluated the accuracy and safety of the implantable Eversense CGM system among adult participants with type 1 and type 2 diabetes. The primary endpoint was the MARD between paired Eversense and Yellow Springs Instrument (YSI) reference measurements through 90 days postinsertion for reference glucose values from 40 to 400 mg/dL. Additional endpoints included Clarke Error Grid analysis and sensor longevity. The primary safety endpoint was the incidence of device-related or sensor insertion/removal procedure-related SAEs through 90 days postinsertion. Ninety participants received the CGM system. The overall MARD value against reference glucose values was 8.8% (95% CI, 8.1%–9.3%), which was significantly lower than the prespecified 20% performance goal for accuracy (P< 0.0001). Ninety-three percent of CGM values were within 20/20% of reference values over the total glucose range of 40 to 400 mg/dL. Clarke Error Grid analysis showed 99.3% of samples in the clinically acceptable error zones A (92.8%) and B (6.5%). Ninety-one percent of sensors were functional through day 90. One related SAE (1.1%) occurred during the study for removal of a sensor. The PRECISE II trial demonstrated that the Eversense CGM system provided accurate glucose readings through the intended 90-day sensor life with a favorable safety profile.

In a prospective multicenter study, Christiansen et al. evaluated the accuracy and safety of Eversense among adults with type 1 or type 2 diabetes through 90 days to further characterize the accuracy of the implantable Eversense CGM system. Accuracy measures included percentage system agreement and MARD between Eversense and YSI reference measurements from 40 to 400 mg/dL. The primary safety endpoint was incidence of device-related or sensor insertion/removal procedure-related SAEs through 90 days. An updated glucose calculation algorithm was also applied to the sensor data from the PRECISE II study to evaluate consistency of accuracy results. Thirty-five participants received the CGM system. Eighty-five percent of CGM values were within 15/15% of reference and the MARD value against reference was 9.6% (95% CI, 8.9–10.4). All sensors were functional through day 90. No device- or procedure-related SAEs occurred. Application of the updated algorithm to PRECISE II sensor data resulted in 87% of readings within 15/15% of reference and a MARD value against reference of 8.5% (95% CI, 8.0%–9.1%). PRECISION corroborated prior accuracy and safety findings of the Eversense CGM System through the 90-day sensor life. The updated algorithm improved accuracy of measurements in PRECISE II.

Three postmarketing registry studies of the Eversense device have been published. Sanchez et al. (2019) reported glucometric and safety data on the first 205 patients in the United States to use the Eversense device for at least 90 days. Of the 205 patients, 62.9% reported having type 1 diabetes, 8.8% type 2 diabetes, and 28.3% were unreported; results were not reported separately by diabetes type. Diess et al. (2019) reported safety outcomes for 3023 patients from 534 sites in Europe and South Africa who had used the device for 6 months or longer. There were no SAEs, and the most commonly reported adverse events were sensor site infection and skin irritation. Tweden et al. (2020) reported accuracy and safety data from 945 patients in Europe and South Africa who used either the 90-day or 180- day Eversense system for four insertion-removal cycles. The percentage of patients using the 180-day system increased from cycle 1 to 4 as the device became more widely available (9%, 39%, 68%, and 88% in cycles 1–4). There was no evidence of degradation of performance of the device over repeated insertion/removal cycles. Adverse events were not otherwise reported.

AUTOMATED INSULIN DELIVERY (AID) SYSTEMS

Automated insulin delivery systems, also known as artificial pancreas device systems (APDS), "closed-loop" systems, or  "autonomous" systems for glycemic control, link a glucose monitor to an insulin infusion pump that automatically takes action (e.g., suspends or adjusts insulin infusion) based on the CGM reading. These devices are proposed to improve glycemic control in patients with insulin-dependent diabetes, particularly reduction of nocturnal hypoglycemia.

An automated insulin delivery system consists of a number of device components that communicate to form a complete system. The FDA describes the basic design as consisting of a CGM system linked to an insulin infusion pump, a BG device such as a glucose meter used to calibrate the CGM, and a computer-controlled algorithm that connects to the CGM and insulin pump to allow for continuous communication between the two devices. FDA-approved AID devices (e.g., MiniMed 670G System, t:slim X2 insulin pump with Basal-IQ technology) have the capability to automatically stop, reduce, or increase insulin infusion based on specified thresholds of measured interstitial glucose.

The three main categories of AID systems, as classed by the FDA, are the threshold suspend device system, insulin-only system, and the bi-hormonal control system. They differ in how the insulin pump acts on readings from the CGM system.

Threshold Suspend Device System

The goal of a threshold suspend device system is to help reverse a dangerous drop in BG level (hypoglycemia) or reduce its severity by temporarily suspending insulin delivery when the glucose level falls to or approaches a low glucose threshold. These are sometimes referred to as "low glucose suspend systems." This kind of system serves as a potential back-up when an individual is unable to respond to a low blood sugar (hypoglycemic) event. Individuals using this system will still need to be active partners in managing their BG levels by periodically checking their BG levels and by giving themselves insulin or eating.

The FDA's approval on September 26, 2013, for the MiniMed 530G with Enlite (i.e., threshold suspend system), a sensor-augmented insulin pump, was based on the results of pivotal clinical studies. In a multicenter, randomized, prospective investigational device exemption study, investigators evaluated the safety and effectiveness of the threshold suspend system in 90 adults with type 1 (n=65) or type 2 diabetes (n=25), who initially were taking an oral antidiabetic agent and now require insulin, with or without an oral agent, and are between the ages of 18 and 75. Sensor accuracy was determined by comparing calibrated glucose sensor values to reference plasma glucose values during in-clinic 12-hour monitoring portions of the study. Individuals were randomly assigned to have two sensors placed on either the abdomen or the buttocks or one on each. There were no symptoms of nausea, vomiting, or abdominal pain during the clinic visits. There were 21 adverse events categorized as being mild intensity and one adverse event categorized as moderate intensity, although none were related to the device or study procedure. The FDA summary of the safety and effectiveness data noted that the performance data presented supported the effectiveness of the device and established the sensor performance across the claimed measuring range (40 to 400 mg/dL glucose). The summary also noted that the risk of inaccurate sensor glucose results was not unreasonably higher than the risk of managing diabetes with a BG meter alone (e.g., incorrect tracking, trending, or threshold detection). The FDA determined that the data provided by the investigators support the reasonable assurance of safety and effectiveness of the device.

In an industry-sponsored study, Bergenstal et al. (2013) evaluated the safety and effectiveness of sensor-augmented insulin pump therapy with and without the threshold suspend feature in individuals with nocturnal hypoglycemia. A total of 247 individuals with type 1 diabetes and documented nocturnal hypoglycemia were randomly assigned to the threshold suspend group (n=121) or standard insulin-pump group (n=126) and followed for up to 3 months. The primary safety outcome measurement was the change in glycated hemoglobin level, and the primary efficacy outcome was the area under the curve (AUC) for nocturnal hypoglycemic events. The changes in glycated hemoglobin values were similar for both groups, although the mean AUC for nocturnal hypoglycemic events was 37.5% lower in the threshold suspend group than in the control group (P<0.001). Four individuals in the control group had a severe hypoglycemic event, and no individuals had diabetic ketoacidosis. The authors concluded that over a 3-month period of use, the threshold suspend feature reduced nocturnal hypoglycemia, without increasing glycated hemoglobin values. The study is limited in its short-term follow-up period.

In a randomized crossover study, Garg et al. (2012) evaluated the safety and effectiveness of automatic suspension of insulin delivery in induced hypoglycemia in 50 individuals with type 1 diabetes who had at least 3 months of experience with an insulin pump. After a 2-week run-in period to optimize basal rates, individuals underwent two in-clinic exercise sessions to induce hypoglycemia. The study outcome, duration of hypoglycemia, was defined as the period of time glucose values were lower than 70 mg/dL and above 50 mg/dL, and hypoglycemia severity was defined as the lowest observed glucose value. A successful exercise session was defined as an observation period of 3 to 4 hours, with glucose levels maintained above 50 mg/dL. The study participants attempted 134 exercise sessions, with 98 being successful. Duration of hypoglycemia was significantly less during the low glucose suspend (LGS)-on sessions than the LGS-off sessions. Hypoglycemia severity was significantly lower in the LGS-on group. The authors concluded that automatic suspension of insulin delivery significantly reduced the duration and severity of induced hypoglycemia. The study is limited in its cross-over design and its short-term follow-up period.

In an RCT, Ly et al. (2013) evaluated the safety and effectiveness of sensor-augmented insulin pump and automated insulin suspensions when compared to standard insulin pump in 95 individuals with type 1 diabetes. Forty-nine individuals were assigned to a control pump–only group, and 46 were assigned to the LGS group. The primary outcome measurement was the rate of moderate to severe hypoglycemic events. The baseline rate was 20.7 events in the pump-only group and 129.6 events in the LGS group, per 100 patient-months. After 6 months of treatment, hypoglycemic event rates decreased from 28 to 16 in the control group and 175 to 35 in the LGS group. The incidence rate ratio was 3.6 (95% CI, 1.7–7.5), representing a statistically significant value ( P<0.001). There was no change in glycated hemoglobin in either group, and there were no episodes of diabetic ketoacidosis or hyperglycemia with ketosis. The authors concluded that sensor-augmented pump therapy with automated insulin suspension reduced the combined rate of severe and moderate hypoglycemia in individuals with type 1 diabetes.

The MiniMed 630G System with SmartGuard™ is similar to the 530G and includes updates to the system components including waterproofing. T he MiniMed 630G System with SmartGuard™ was approved on August 10, 2016, by the FDA for continuous delivery of basal insulin (at user selected rates) and administration of insulin boluses (in user selectable amounts) for the management of diabetes mellitus in individuals 16 years of age and older, requiring insulin as well as for the continuous monitoring and trending of glucose levels in the fluid under the skin. The Minimed 630G System includes SmartGuard™, which can be programmed to temporarily suspend delivery of insulin for up to 2 hours when the sensor glucose value falls below a predefined threshold value.

The t:slim X2 Insulin Pump with Basal-IQ Technology System was approved by the FDA on June 21, 2018, for individuals 6 years of age and older. The System consists of the t:slim X2 Insulin Pump paired with the Dexcom G5 or Dexcom G6 CGM, as well as the Basal-IQ Technology. The t:slim X2 Insulin Pump is intended for the subcutaneous delivery of insulin, at set and variable rates, for the management of diabetes mellitus in individuals requiring insulin. The t:slim X2 Insulin Pump can be used solely for continuous insulin delivery and as part of the System as the receiver for a therapeutic CGM. The t:slim X2 Insulin Pump running the Basal-IQ Technology can be used to suspend insulin delivery based on CGM sensor readings.

Insulin-Only System

Hybrid Closed Loop Device System
An insulin-only system achieves a target glucose level by increasing or decreasing the amount of basal insulin infused, as set using an automated feature. These systems can function as a hybrid system that automatically adjusts basal insulin by the user manually delivering bolus insulin to cover meals, or could be fully closed loop systems, where the system can be programmed to automatically adju st basal insulin and provide insulin for meals.

The Minimed 780G system, by Medtronic, was approved by the FDA, on April 21, 2023, and is intended for continuous delivery of basal insulin at selectable rates and the administration of insulin boluses at selectable amounts for the management of type I diabetes mellitus in individuals ages 7 years and older requiring insulin. The Minimed 780G system includes SmartGuard (SG) technology, which can be programmed to automatically adjust insulin delivery based on CGM glucose sensor values and can suspend delivery of insulin when the SG value falls below or is predicted to fall below predefined threshold values. 

The MiniMed 670G system, by Medtronic, was approved by the FDA, on September 28, 2016, as the world's first hybrid closed loop device system. The 670G is approved for the management of individuals ages 14 years and older with type 1 diabetes, requiring insulin, as well as CGM. The Minimed 670G allows for continuous delivery of basal insulin, as well as the administration of insulin boluses, as determined by the user. The MiniMed 670G system includes SmartGuard technology, which can be programmed to automatically adjust delivery of basal insulin based on CGM values, and can suspend delivery of insulin when the sensor glucose value falls below or is predicted to fall below predefined threshold values. The MiniMed 670G sensors are FDA approved and useable for 7 days, while the transmitters are approved and useable for a year. This system is an adjunctive device and therapy adjustments should be based on measurements obtained using a standard BG monitor and not on values provided by the sensor.  

The approval of the MiniMed 670G system was based on results of a pivotal clinical multicenter, single-arm study, that involved the clinical evaluation of 124 participating individuals; 30 adolescents, ranging from 14 to 21 years of age, and 94 adults, who were 22 to 75 years of age, at 10 investigational centers, from June 3, 2015, through March 7, 2016.

The study criteria included individuals with type 1 diabetes for 2 or more years on insulin pump therapy, with a history of two or more episodes of severe hypoglycemia, during the 6 months prior to screening, and their HbA1C level was less than 10.0%. There was no parallel control group.

The clinical trial included an initial 2-week period where the MiniMed 670G hybrid closed loop device system's SAP function was used and not the automated features that adjust insulin delivery. The study then involved a 3-month period at home during which individuals in the clinical trial used the system's hybrid closed loop automated feature as frequently as possible, followed by a 5-day/6-night hotel stay, as part of the trial.

The results of the clinical trial revealed that the MiniMed 670G hybrid closed loop device system was able to lower the A1c level an average of 0.5%, in individuals 14 years of age and older with type 1 diabetes, using the automated features.

The MiniMed 770G System is an iteration of the MiniMed 670G System and was approved by the FDA on August 31, 2020. The 770G is intended for continuous delivery of basal insulin (at user selectable rates) and administration of insulin boluses (in user selectable amounts) for the management of type 1 diabetes mellitus in individuals 2 years of age and older.

On December 13, 2019, the FDA approved Tandem's Control-IQ technology in individuals 14 years and older for the management of type 1 diabetes. Control-IQ is intended for use with compatible integrated continuous glucose monitors (iCGM) and alternate controller enabled (ACE) pumps to automatically increase, decrease, and suspend delivery of basal insulin based on iCGM readings and predicted glucose values. It can also deliver correction boluses when the glucose value is predicted to exceed a predefined threshold. Control-IQ combines the t:stlim X2 insulin pump, the Dexcom G6 CGM, and an algorithm built into the pump that adjusts basal insulin delivery and gives automatic correction boluses.

Closed Loop Device System​

On May 19, 2023, the FDA approved the iLet® ACE Pump and iLet® Dosing Decision Software for individuals 6 years of age and older with type 1 diabetes. These two devices, along with a compatible FDA-cleared iCGM, will form a new system called the iLet Bionic Pancreas. This AID system uses an algorithm to determine and command insulin delivery.

Currently, the iLet Bionic Pancreas (Beta Bionics) is the only closed-loop automated insulin delivery system commercially available in the United States. The system differs from hybrid closed-loop systems in that it is initialized only with a user's body weight and doses insulin autonomously without carbohydrate counting. Hybrid closed-loop systems require individualized insulin regimens and require the user to count the grams of carbohydrates to be eaten and then enter this number into their device's user interface. In contrast, the closed-loop insulin delivery system is initialized only based on body weight and requires only that the user make a qualitative estimate of carbohydrate content that is relative to what is usual for the user (“Usual For Me", “More", or “Less") compared to a typical meal of that type (“Breakfast", “Lunch", or “Dinner"). In response to qualitative meal announcements to the system by the user, the system delivers approximately 75% of the autonomously estimated insulin immediately and then autonomously adjusts insulin dosing postprandially as needed. Additionally, the device includes a feature that enables continued insulin delivery when CGM information is not available, based on a basal insulin profile autonomously determined and continually updated. Use of this feature, however, is intended to be temporary, with the goal to resume CGM-guided insulin dosing as soon as possible.  The system was developed as both an insulin-only system and a bihormonal system that administers both insulin and glucagon. Currently, only the insulin-only system has FDA clearance.

Bi-Hormonal Control System

The bi-hormonal control system achieves a target glucose level by using two algorithms to instruct an infusion pump to deliver two different hormones: one hormone (insulin) to lower glucose levels and another (such as glucagon) to increase BG levels. The bi-hormonal control system mimics the glucose-regulating function of a healthy pancreas more closely than an insulin-only system. These systems are still being investigated.