Control-IQ+ technology

K243823 · Tandem Diabetes Care, Inc. · QJI · Feb 24, 2025 · Clinical Chemistry

Device Facts

• Record ID: K243823
• Device Name: Control-IQ+ technology
• Applicant: Tandem Diabetes Care, Inc.
• Product Code: QJI · Clinical Chemistry
• Decision Date: Feb 24, 2025
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1356
• Device Class: Class 2
• Attributes: Software as a Medical Device, Therapeutic, Pediatric

Indications for Use

Control-IQ+ technology 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+ technology is intended for the management of Type 1 diabetes mellitus in persons 2 years of age and greater and of Type 2 diabetes mellitus in persons 18 years of age and greater. Control-IQ+ technology is intended for single patient use and requires a prescription.

Device Story

Control-IQ+ is a software-only interoperable automated glycemic controller installed on compatible ACE insulin pumps. It receives real-time glucose data from integrated continuous glucose monitors (iCGM) and user inputs (carbohydrate intake, exercise, sleep schedule). The device uses a closed-loop algorithm to automatically adjust basal insulin delivery and administer correction boluses based on predicted glucose values. It operates in three modes: Normal, Sleep, and Exercise, each with specific glucose target ranges. The system requires initial user configuration of weight and total daily insulin requirements. By automating insulin adjustments, the device assists patients in maintaining glucose levels within target ranges, reducing the burden of manual insulin management. It is intended for single-patient use in home or clinical settings, operated by the patient or caregiver.

Clinical Evidence

Prospective, multi-center, randomized controlled trial (2IQP) of 319 adults with T2D (215 AID, 104 CGM control). Primary endpoint: change in HbA1c over 13 weeks. AID group HbA1c decreased from 8.2% to 7.3% vs. 8.1% to 7.7% in control (adjusted difference -0.6%, 95% CI -0.8%, -0.4%, p<0.001). Secondary endpoint: Time in Range (70-180 mg/dL) increased by 14% in AID group vs. 1% in control (p<0.001). Safety: 1 severe hypoglycemia event (unclear attribution), no DKA. Human factors validation performed on 30 T2D subjects.

Technological Characteristics

Software-only device; interoperable with iCGM and ACE pumps. Operates via closed-loop algorithm with three modes (Normal, Sleep, Exercise) and predefined glucose target ranges. Requires user input for weight and total daily insulin. Adheres to IEC 62366-1 for usability. No changes to algorithm design compared to predicate.

Indications for Use

Indicated for management of Type 1 diabetes mellitus in persons ≥2 years and Type 2 diabetes mellitus in persons ≥18 years. Contraindicated for patients requiring <5 units total daily insulin or weighing <20 lbs. Do not use if taking hydroxyurea.

Regulatory Classification

Identification

An interoperable automated glycemic controller is a device intended to automatically calculate drug doses based on inputs such as glucose and other relevant physiological parameters, and to command the delivery of such drug doses from a connected infusion pump. Interoperable automated glycemic controllers are designed to reliably and securely communicate with digitally connected devices to allow drug delivery commands to be sent, received, executed, and confirmed. Interoperable automated glycemic controllers are intended to be used in conjunction with digitally connected devices for the purpose of maintaining glycemic control.

Special Controls

*Classification.* Class II (special controls). The special controls for this device are:(1) Design verification and validation must include: (i) An appropriate, as determined by FDA, clinical implementation strategy, including data demonstrating appropriate, as determined by FDA, clinical performance of the device for its intended use, including all of its indications for use. (A) The clinical data must be representative of the performance of the device in the intended use population and in clinically relevant use scenarios and sufficient to demonstrate appropriate, as determined by FDA, clinical performance of the device for its intended use, including all of its indications for use. (B) For devices indicated for use with multiple therapeutic agents for the same therapeutic effect ( *e.g.,* more than one type of insulin), data demonstrating performance with each product or, alternatively, an appropriate, as determined by FDA, clinical justification for why such data are not needed.(C) When determined to be necessary by FDA, the strategy must include postmarket data collection to confirm safe real-world use and monitor for rare adverse events. (ii) Results obtained through a human factors study that demonstrates that an intended user can safely use the device for its intended use. (iii) A detailed and appropriate, as determined by FDA, strategy to ensure secure and reliable means of data transmission with other intended connected devices. (iv) Specifications that are appropriate, as determined by FDA, for connected devices that shall be eligible to provide input to ( *e.g.,* specification of glucose sensor performance) or accept commands from (*e.g.,* specifications for drug infusion pump performance) the controller, and a detailed strategy for ensuring that connected devices meet these specifications.(v) Specifications for devices responsible for hosting the controller, and a detailed and appropriate, as determined by FDA, strategy for ensuring that the specifications are met by the hosting devices. (vi) Documentation demonstrating that appropriate, as determined by FDA, measures are in place ( *e.g.,* validated device design features) to ensure that safe therapy is maintained when communication with digitally connected devices is interrupted, lost, or re-established after an interruption. Validation testing results must demonstrate that critical events that occur during a loss of communications (*e.g.,* commands, device malfunctions, occlusions, etc.) are handled and logged appropriately during and after the interruption to maintain patient safety.(vii) A detailed plan and procedure for assigning postmarket responsibilities including adverse event reporting, complaint handling, and investigations with the manufacturers of devices that are digitally connected to the controller. (2) Design verification and validation documentation must include appropriate design inputs and design outputs that are essential for the proper functioning of the device that have been documented and include the following: (i) Risk control measures to address device system hazards; (ii) Design decisions related to how the risk control measures impact essential performance; and (iii) A traceability analysis demonstrating that all hazards are adequately controlled and that all controls have been validated in the final device design. (3) The device shall include appropriate, as determined by FDA, and validated interface specifications for digitally connected devices. These interface specifications shall, at a minimum, provide for the following: (i) Secure authentication (pairing) to connected devices; (ii) Secure, accurate, and reliable means of data transmission between the controller and connected devices; (iii) Sharing of necessary state information between the controller and any connected devices ( *e.g.,* battery level, reservoir level, sensor use life, pump status, error conditions);(iv) Ensuring that the controller continues to operate safely when data is received in a manner outside the bounds of the parameters specified; (v) A detailed process and procedures for sharing the controller's interface specification with connected devices and for validating the correct implementation of that protocol; and (vi) A mechanism for updating the controller software, including any software that is required for operation of the controller in a manner that ensures its safety and performance. (4) The device design must ensure that a record of critical events is stored and accessible for an adequate period to allow for auditing of communications between digitally connected devices, and to facilitate the sharing of pertinent information with the responsible parties for those connected devices. Critical events to be stored by the controller must, at a minimum, include: (i) Commands issued by the controller, and associated confirmations the controller receives from digitally connected devices; (ii) Malfunctions of the controller and malfunctions reported to the controller by digitally connected devices ( *e.g.,* infusion pump occlusion, glucose sensor shut down);(iii) Alarms and alerts and associated acknowledgements from the controller as well as those reported to the controller by digitally connected devices; and (iv) Connectivity events ( *e.g.,* establishment or loss of communications).(5) The device must only receive glucose input from devices cleared under § 862.1355 (integrated continuous glucose monitoring system), unless FDA determines an alternate type of glucose input device is designed appropriately to allow the controller to meet the special controls contained within this section. (6) The device must only command drug delivery from devices cleared under § 880.5730 of this chapter (alternate controller enabled infusion pump), unless FDA determines an alternate type of drug infusion pump device is designed appropriately to allow the controller to meet the special controls contained within this section. (7) An appropriate, as determined by FDA, training plan must be established for users and healthcare providers to assure the safety and performance of the device when used. This may include, but not be limited to, training on device contraindications, situations in which the device should not be used, notable differences in device functionality or features compared to similar alternative therapies, and information to help prescribers identify suitable candidate patients, as applicable. (8) The labeling required under § 809.10(b) of this chapter must include: (i) A contraindication for use in pediatric populations except to the extent clinical performance data or other available information demonstrates that it can be safely used in pediatric populations in whole or in part. (ii) A prominent statement identifying any populations for which use of this device has been determined to be unsafe. (iii) A prominent statement identifying by name the therapeutic agents that are compatible with the controller, including their identity and concentration, as appropriate. (iv) The identity of those digitally connected devices with which the controller can be used, including descriptions of the specific system configurations that can be used, per the detailed strategy submitted under paragraph (b)(1)(iii) of this section. (v) A comprehensive description of representative clinical performance in the hands of the intended user, including information specific to use in the pediatric use population, as appropriate. (vi) A comprehensive description of safety of the device, including, for example, the incidence of severe hypoglycemia, diabetic ketoacidosis, and other relevant adverse events observed in a study conducted to satisfy paragraph (b)(1)(i) of this section. (vii) For wireless connection enabled devices, a description of the wireless quality of service required for proper use of the device. (viii) For any controller with hardware components intended for multiple patient reuse, instructions for safely reprocessing the hardware components between uses.

Predicate Devices

• Control-IQ technology (K232382)

Submission Summary (Full Text)

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FDA

U.S. FOOD &amp; DRUG

ADMINISTRATION

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

## I Background Information:

A 510(k) Number

K243823

B Applicant

Tandem Diabetes Care, Inc.

C Proprietary and Established Names

Control-IQ+ technology

D Regulatory Information

| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| QJI | Class II | 21 CFR 862.1356 - Interoperable Automated Glycemic Controller | CH - Clinical Chemistry |

## E Purpose for Submission:

The purpose of this submission is an expansion of the indications for use (IFU) to include type 2 diabetes mellitus in persons 18 years of age and greater.

## II Intended Use/Indications for Use:

A Intended Use(s):

See Indications for Use below.

B Indication(s) for Use:

Control-IQ+ technology 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.

Food and Drug Administration

10903 New Hampshire Avenue

Silver Spring, MD 20993-0002

www.fda.gov

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Control-IQ+ technology is intended for the management of Type 1 diabetes mellitus in persons 2 years of age and greater and of Type 2 diabetes mellitus in persons 18 years of age and greater.

Control-IQ+ technology is intended for single patient use and requires a prescription.

## C Special Conditions for Use Statement(s):

Rx - For Prescription Use Only

Only use U-100 insulin analogs that have been tested and found to be compatible for use in the pump. Use of insulin with lesser or greater concentration can result in under delivery or over delivery of insulin. This can cause hypoglycemia (low BG) or hyperglycemia (high BG) events.

When the CGM reading is automatically populated into the bolus calculator, only the current CGM reading is used to calculate the correction bolus. The trend arrow is not used in the dose calculation. Speak with your healthcare provider for recommendations on how best to utilize the arrows for your correction bolus dosing.

Control-IQ+ should not be used in anyone under the age of two years old. Control-IQ+ should also not be used in patients who require less than a total daily insulin dose of 5 units per day or who weigh less than 20 pounds, as those are the required minimum values needed in order for Control-IQ technology to operate safely.

The System is magnetic resonance (MR) unsafe. You must take off your pump, transmitter, and sensor and leave them outside the procedure room.

DO NOT use Control-IQ+ if you are taking hydroxyurea, a medication used in the treatment of diseases including cancer and sickle cell anemia. Your Dexcom G6 CGM readings may be falsely elevated and result in over-delivery of insulin that could result in severe hypoglycemia.

## III Device/System Characteristics:

Control-IQ+ technology (Control-IQ+, the device) is a software-only device intended for the management of type 1 and type 2 diabetes mellitus. The device controls insulin delivery from a compatible alternate controller enabled insulin pump (ACE pump) based on inputs provided by a compatible integrated continuous glucose monitor (iCGM) and inputs provided by the user (e.g., carbohydrate intake, exercise, and sleep schedule). Control-IQ+ technology is meant to be installed on a compatible ACE pump.

Control-IQ+ technology has three different modes: Normal, Sleep, and Exercise. The glucose targets are not individually customizable in these modes but can change based on the mode selected. During normal mode, Control-IQ+ technology aims to control glucose within a target range of 112.5 – 160 mg/dL. During sleep mode, this range is changed to 112.5-120 mg/dL, and it is changed to 140-160 mg/dL during exercise mode.

Control-IQ+ technology includes an integrated feature whereby iCGM values are automatically populated into the glucose field of the integrated bolus calculator when Control-IQ+ technology is active (i.e., the device is operating in closed-loop mode). This feature is disabled when Control-IQ is turned off.

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Control-IQ+ technology requires users to input their weight and their total daily insulin requirement, which should be established with the help of a health care provider before using the device.

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## IV Substantial Equivalence Information:

### A Predicate Device Name(s):

Control-IQ technology

### B Predicate 510(k) Number(s):

K232382

### C Comparison with Predicate(s):

| Device & Predicate Device(s): | K243823 | K232382 |
| --- | --- | --- |
| Device Trade Name | Control-IQ+ technology | Control-IQ technology |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | 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. | Same |
| General Device Characteristic Differences | | |
| Intended Use Population | Control-IQ+ technology is intended for the management of Type 1 diabetes mellitus in persons 2 years of age and greater and of Type 2 diabetes mellitus in persons 18 years of age and greater. | Control-IQ technology is intended for the management of Type 1 diabetes mellitus in persons 2 years of age and greater. |

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V Standards/Guidance Documents Referenced:

Special controls established under 21 CFR 862.1356.

ISO 14971:2007: Medical Devices - Application of Risk Management to Medical Devices FDA Recognition No: 5-40

IEC 62366-1 Edition 1.1 2020-06 CONSOLIDATED VERSION, Medical devices - Part 1: Application of usability engineering to medical devices

VI Performance Characteristics (if/when applicable):

A Analytical Performance:

For the purposes of analytical and clinical validation testing, the Control-IQ algorithm was installed on the t:slim X2 Insulin Pump with Interoperable Technology ACE pump (K232380), which was paired with the Dexcom G6 continuous glucose monitoring system (K223931).

B Other Supportive Instrument Performance Characteristics Data:

Summary of Clinical Testing:

The sponsor conducted a prospective, multi-center, randomized controlled study to compare the use of Control-IQ+ technology (or automated insulin dosing (AID) group) to the use of a continuous glucose monitor (CGM) with basal-bolus insulin therapy (or CGM group). The randomized controlled phase (Primary Study) was 13 weeks in duration.

A summary of the pivotal clinical study is provided in the following table (Control-IQ+ technology group abbreviated as AID):

| Study Feature | Description |
| --- | --- |
| Title | A Randomized Trial Evaluating the Efficacy and Safety of Control-IQ Technology in Adults with Type 2 Diabetes Using Basal-Bolus Insulin Therapy (2IQP) |
| Summary | Randomized controlled trial in adults with type 2 diabetes comparing the use of Tandem t:slim X2 insulin pump with Control-IQ+ technology and Dexcom G6 (AID treatment group) in adults with type 2 diabetes on basal-bolus insulin versus continued care with Dexcom G6 (CGM control group). |
| Investigational Device | t:slim X2 insulin pump with Control-IQ+ technology |
| Objectives | The objective of the study is to assess efficacy and safety of a closed loop system (Control-IQ+ technology) in adults with type 2 diabetes in a randomized controlled trial. |

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| Study Design | Randomized Clinical Trial with 2:1 randomization to intervention with the closed loop system vs. sensor-augmented basal-bolus insulin delivery for 13 - 17 weeks. |
| --- | --- |
| Number of Sites | 21 clinical sites (19 in the United States, 2 in Canada). |
| Population | There were 319 subjects ages 19 to 87, diabetes duration 1 to 59 years, and baseline HbA1c 5.2% to 14.1% (mean 8.2±1.3%).

Key Inclusion Criteria:
• Clinical diagnosis of type 2 diabetes of at least 6 months
• Using basal-bolus insulin therapy or an insulin pump for at least 3 months
• If using noninsulin glucose lowering medications, dose stable for prior 3 months

Key Exclusion Criteria:
• Current use of hybrid closed-loop system
• Use of systemic glucocorticoids, sulfonylurea or hydroxyurea |
| Sample Size | 319 participants completed the randomized trial, with 215 in the intervention arm and 104 in the control arm. |
| Treatment Groups | Randomized Trial
• Intervention Group: t:slim X2 with Control-IQ+ technology and Dexcom G6 iCGM.
• Control Group: Basal-Bolus insulin with Dexcom G6 iCGM. |
| Study Duration | 13 to 17 weeks depending on participation in run-in period. |

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| Protocol Overview/Synopsis | After consent was signed, eligibility was assessed. Eligible participants not currently using a Dexcom G6 continuous glucose monitor (CGM), or not meeting CGM usage requirements, initiated a run-in phase of 3 to 4 weeks that was customized based on whether the participant was already a CGM user. Participants continued to use their personal insulin delivery method (pump or MDI) during the CGM Run-in.

Participants who skipped or successfully completed the run-in were randomly assigned 2:1 to an intervention group using t:slim X2 insulin pump with Control-IQ+ technology and CGM (AID group) or the control group using the continuation of pre-study basal-bolus insulin delivery method in conjunction with study CGM (CGM group).

At randomization and the 13-week visit, a blood sample was obtained for central lab HbAlc determination. At screening and at the 13-week visit, patient reported outcomes were completed. Participants in the AID group were asked to perform 3 meal challenges and (if found to be medically eligible) 3 exercise challenges. |
| --- | --- |
| Safety Results | There was 1 severe hypoglycemia event during the study period but it was unclear if it was attributable to the device. The subject was able to treat this appropriately at home.

There were no other severe hypoglycemia or diabetic ketoacidosis events during the study. There were 25 serious adverse events not related or unlikely to be related to the study device or treatments. |

Participant Demographics

| | AID Group
N = 215 | CGM Group
N = 104 |
| --- | --- | --- |
| Age (years) | | |
| Mean ± SD | 59 ± 12 | 57 ± 12 |
| Range | 19 to 87 | 23 to 80 |
| Sex – Female n (%) | 105 (49%) | 49 (47%) |
| Weight (kg) | | |
| Median (IQR) | 99 (84, 117) | 103 (0.6, 1.2) |
| Range | 49 to 164 | 0.2 to 3.6 |
| BMI (kg/m²) | | |
| Median (IQR) | 33 (29, 40) | 35 (29, 40) |
| Range | 19 to 56 | 20 to 57 |

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## Race

| White | 148 (69%) | 74 (71%) |
| --- | --- | --- |
| Black / African American | 45 (21%) | 24 (23%) |
| Asian | 10 (5%) | 3 (3%) |
| Native Hawaiian / Other Pacific Islanders | 2 (<1%) | 0 (0%) |
| American Indian / Alaskan Native | 1 (<1%) | 1 (<1%) |
| More than one race | 6 (3%) | 2 (2%) |
| Unknown / Not reported | 3 (1%) | 0 (0%) |

## Ethnicity

| Hispanic or Latino | 23 (11%) | 11 (11%) |
| --- | --- | --- |
| Non-Hispanic or Latino | 190 (88%) | 93 (89%) |
| Unknown/not reported | 2 (<1%) | 0 (0%) |

## Education

| < High School Diploma | 8 (4%) | 3 (3%) |
| --- | --- | --- |
| High School Diploma / GED | 57 (27%) | 21 (20%) |
| Technical/Vocational | 25 (12%) | 12 (12%) |
| Associate Degree | 33 (15%) | 16 (15%) |
| College Graduate | 49 (23%) | 32 (31%) |
| Advanced Degree | 33 (15%) | 16 (15%) |
| Unknown | 1 (<1%) | 0 (0%) |
| Do not wish to provide | 9 (4%) | 4 (4%) |

## Annual Household Income

| <$50,000 | 60 (28%) | 26 (25%) |
| --- | --- | --- |
| $50,000-<$100,000 | 52 (24%) | 21 (20%) |
| $100,000 or more | 53 (25%) | 36 (35%) |
| Unknown | 11 (5%) | 5 (5%) |
| Does not wish to report | 39 (18%) | 16 (15%) |

## Health Insurance

| Private | 116 (54%) | 65 (63%) |
| --- | --- | --- |
| Medicare | 57 (27%) | 15 (14%) |
| Medicaid | 10 (5%) | 13 (13%) |
| Other government insurance | 23 (11%) | 8 (8%) |
| No coverage | 2 (<1%) | 2 (2%) |
| Unknown / No answer | 7 (3%) | 1 (<1%) |

## Participant Diabetes History

| | AID Group
N = 215 | CGM Group
N = 104 |
| --- | --- | --- |
| Diabetes Duration (yrs) | | |
| <5 | 11 (5%) | 9 (9%) |
| 5-<10 | 31 (15%) | 10 (10%) |
| 10-<20 | 71 (42%) | 39 (38%) |
| ≥20 | 102 (38%) | 46 (44%) |
| Median (IQR) | 18 (11, 24) | 18 (11, 24) |
| Range | 1 to 59 | 2 to 45 |
| Insulin Modality | | |
| MDI | 206 (96%) | 100 (96%) |

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| Pump | 9 (4%) | 4 (4%) |
| --- | --- | --- |
| Insulin | | |
| Insulin pump with rapid acting analog | 9 (4%) | 4 (4%) |
| Once daily basal insulin with rapid acting analog multiple times per day | 156 (73%) | 74 (71%) |
| Once daily basal insulin with regular insulin multiple times per day | 2 (<1%) | 0 |
| Twice daily U-500 with or without a rapid acting analog multiple times per day | 2 (<1%) | 0 |
| Twice daily basal insulin with a rapid acting analog multiple times per day | 36 (17%) | 21 (20%) |
| Twice daily basal insulin with regular insulin multiple times per day | 5 (2%) | 4 (4%) |
| Twice daily premixed insulin | 5 (2%) | 1 (<1%) |
| Non-Insulin Glucose Lowering Medications n (%) | | |
| Metformin | 109 (51%) | 61 (59%) |
| SGLT-2 inhibitor | 76 (35%) | 41 (39%) |
| GLP-1 agonist | 87 (40%) | 54 (52%) |
| SGLT-2 inhibitor and GLP-1 Agonist | 44 (20%) | 24 (23%) |
| Othera | 9 (4%) | 10 (10%) |
| Prior Continuous Glucose Monitor Use | | |
| Current | 147 (68%) | 78 (75%) |
| In past, but not current | 40 (19%) | 16 (15%) |
| Never | 28 (13%) | 10 (10%) |
| HbA1c – Local at enrollment | | |
| <7.0% | 28 (13%) | 15 (14%) |
| 7.0% to <8.0% | 73 (34%)0 | 40 (38%) |
| 8.0% to <9.0% | 66 (31%) | 24 (23%) |
| ≥9.0% | 47 (22%) | 25 (24%) |
| Mean (SD) | 8.2 (1.4) | 8.1 (1.2) |
| Range | 5.7 to 14.1 | 5.2 to 12.4 |
| Total Daily Insulin (units/kg/day) | | |
| Median (IQR) | 0.9 (0.6, 1.2) | 0.9 (0.6, 1.2) |
| Range | 0.2 to 2.7 | 0.2 to 3.6 |
| Severe Events prior 12 months | | |
| Severe hypoglycemia ever | 5 (2%) | 3 (3%) |
| Diabetic ketoacidosis ever | 4 (2%) | 2 (2%) |
| Hyperosmolar hyperglycemic state ever | 0 | 1 (<1%) |
| c-Peptideb (nmol/L) – Median (IQR) | 0.76 (0.46, 1.2) | 0.86 (0.50, 1.3) |
| GAD Antibody (IU/mL) – n (%) | | |
| <5.0 | 202 (94%) | 92 (88%) |
| 5.0 to <250 | 3 (1%) | 8 (8%) |
| ≥250 | 10 (5%) | 4 (4%) |

a - Other medications included alogliptin, linagliptin, pioglitazone, and sitagliptin
b - For c-Peptide, 0.007 is lab's detectable limit

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Observed Results

The primary endpoint evaluated the non-inferiority of the change in HbA1c at baseline to the end of 13 weeks between the intervention group (AID group) and control group (CGM group). HbA1c changed from $8.2 \pm 1.4\%$ at randomization to $7.3 \pm 0.9\%$ at 13 weeks in the AID group, compared to $8.1 \pm 1.2\%$ at randomization to $7.7 \pm 1.1\%$ at 13 weeks for the CGM group. The AID group had a 13-week adjusted group different from the CGM group of $-0.6\%$ with a $95\%$ confidence interval of $-08\%$ , $-0.4\%$ .

HbA1c group comparison

| | AID group | CGM Group |
| --- | --- | --- |
| Baseline (n) | n=214a | n=104 |
| Baseline mean HbA1c (SD) | 8.2% (1.4%) | 8.1% (1.2%) |
| 13 weeks (n) | n=209b | n=102c |
| 13 weeks mean HbA1c (SD) | 7.3% (0.9%) | 7.7% (1.1%) |
| Change from Baseline mean HbA1c | -0.9% (1.1%) | -0.3% (0.9%) |
| 13 week Adjusted Group Difference (95% CI)d [p-value] | -0.6% (-0.8%, -0.4%) [<0.001] | |

a - missing (sample not analyzable) for one participant
b - Four participants dropped prior to 13 weeks final visit. The sample for one participant not analyzable. The sample for one participant was collected outside the pre-specified analysis window and thus not included.
c - Two participants dropped prior to 13 weeks final visit.
d - The difference is AID group - CGM group. Direct likelihood was used to handle missing data. The model adjusted for the baseline HbA1c and for site as a random effect.

A key secondary endpoint evaluated the non-inferiority of the change in CGM time in range (70 - 180 mg/dL) at baseline to the end of 13 weeks between the intervention group (AID group) and control group (CGM group). CGM time in range changed from $48 \pm 24\%$ at randomization to 64 $\pm 16\%$ at 13 weeks in the AID group, compared to $51 \pm 21\%$ at randomization to $52 \pm 21\%$ at 13 weeks for the CGM group. The AID group had a 13-week adjusted group different from the CGM group of $14\%$ with a $95\%$ confidence interval of $11\%$ , $17\%$ .

CGM percent time in range (70 - 180 mg/dL) group comparison

| | AID Group | CGM Group |
| --- | --- | --- |
| Baseline mean (SD) | 48% (24%) | 51% (21%) |
| 13 weeks mean (SD) | 64% (16%) | 52% (21%) |
| Change from Baseline mean (SD) | 16% (19%) | 1% (14%) |
| 13-week Adjusted\(^a\) Group Difference (95% CI) [p-value] | 14% (11%, 17%) [<0.001] | |

a - The model adjusted for the baseline HbA1c and for site as a random effect.

Subgroup analyses support that improvement in HbA1c after 13 weeks of AID use were seen across the AID group and were greater than from the CGM group and were similar across the distribution of age, sex, racial or ethnic minorities, diabetes duration, baseline bolus method, and prior insulin regimen. The table below depicts HbA1c and (SD). N values correspond to week 13.

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Subgroup analysis of change in HbA1c over 13 weeks

| | AID | | | CGM | | |
| --- | --- | --- | --- | --- | --- | --- |
| | N | Baseline mean % (SD) | Change from Baseline mean % (SD) | N | Baseline mean % (SD) | Change from Baseline mean % (SD) |
| Overall | 208 | 8.2 (1.4) | -0.9 (1.1) | 102 | 8.0 (1.1) | -0.3 (0.9) |
| Baseline lab HbA1c | | | | | | |
| <7.0% | 28 | 6.4 (0.4) | -0.0 (0.4) | 15 | 6.5 (0.4) | 0.0 (0.4) |
| 7.0% to <8.0% | 71 | 7.5 (0.3) | -0.5 (0.6) | 40 | 7.5 (0.3) | -0.1 (0.6) |
| 8.0% to <9.0% | 65 | 8.4 (0.3) | -0.9 (0.7) | 24 | 8.3 (0.3) | -0.2 (0.8) |
| >9.0% | 44 | 10.3 (1.2) | -2.3 (1.2) | 23 | 9.7 (0.6) | -1.0(1.1) |
| Baseline time in range (70-180 mg/dL) | | | | | | |
| >60% | 79 | 7.4 (0.9) | -0.4 (0.8) | 39 | 7.3 (0.7) | -0.2 (0.7) |
| 30% to <60% | 77 | 8.2 (0.9) | -0.8 (0.8) | 44 | 8.1 (0.9) | -0.2 (0.9) |
| <30% | 52 | 9.5 (1.5) | -2.0 (1.2) | 19 | 9.4 (0.8) | -0.6 (1.0) |
| Non-insulin glucose lowering medications | | | | | | |
| None | 46 | 8.7 (1.7) | -1.4 (1.3) | 12 | 8.7 (1.1) | -0.4 (1.4) |
| Other, but no SGLT-2i or GLP-Ira | 48 | 8.3 (1.5) | -1.0 (1.2) | 20 | 8.3 (1.0) | -0.3 (0.9) |
| GLP-1ra, but no SGLT-2i | 42 | 8.1 (1.3) | -0.8 (0.9) | 29 | 7.8 (1.1) | -0.4 (0.8) |
| SGLT-2i, but no GLP-1ra | 29 | 8.2 (0.9) | -0.7 (0.8) | 17 | 7.8 (1.2) | -0.3 (0.7) |
| Both GLP-1ra and SGLT-2i | 43 | 7.9 (1.1) | -0.8 (1.0) | 24 | 7.8 (1.1) | -0.1 (0.7) |
| BMI (kg/m2) | | | | | | |
| <30 | 58 | 8.3 (1.6) | -0.9 (1.2) | 30 | 8.2 (1.1) | -0.5 (1.0) |
| 30 to <35 | 71 | 8.3 (1.3) | -1.0 (1.1) | 24 | 8.3 (1.2) | -0.5 (0.9) |
| 35 to <40 | 32 | 7.9 (0.9) | -0.8 (0.7) | 26 | 7.7 (1.2) | -0.2 (0.4) |
| >40 | 47 | 8.3 (1.5) | -1.0 (1.1) | 22 | 7.9 (0.9) | 0.0 (0.8) |
| Total daily insulin (units/day) | | | | | | |
| <100 | 125 | 8.3 (1.5) | -1.0 (1.1) | 57 | 7.9 (1.0) | -0.3 (0.7) |
| 100 to <150 | 55 | 8.1 (1.1) | -0.9 (1.0) | 27 | 8.2 (1.3) | -0.3 (0.8) |
| 150 to <200 | 14 | 8.0 (0.8) | -0.6 (0.7) | 12 | 7.7 (0.8) | 0.2 (1.0) |
| >200 | 14 | 7.9 (1.3) | -0.9 (1.2) | 6 | 8.7 (1.7) | -1.0 (1.4) |
| Sex | | | | | | |
| Female | 100 | 8.4 (1.5) | -1.0 (1.2) | 48 | 8.0 (1.1) | -0.4 (1.0) |
| Male | 108 | 8.0 (1.2) | -0.8 (1.0) | 54 | 8.0 (1.1) | -0.2 (0.7) |
| Age at enrollment (years) | | | | | | |
| <50 | 48 | 8.7 (1.7) | -1.5 (1.4) | 29 | 8.2 (1.4) | -0.2 (1.0) |
| 50 to <65 | 83 | 8.3 (1.3) | -1.0 (1.1) | 48 | 8.0 (1.0) | -0.4 (0.9) |
| >65 | 77 | 7.8 (1.0) | -0.6 (0.7) | 25 | 7.9 (1.0) | -0.2 (0.6) |
| Diabetes duration at enrollment (years) | | | | | | |
| <5 | 10 | 8.5 (1.6) | -1.3 (1.3) | 9 | 8.3 (0.6) | -0.3 (1.3) |

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| 5 to <10 | 29 | 8.5 (1.3) | -1.3 (1.1) | 10 | 8.4 (1.4) | -0.6 (1.3) |
| --- | --- | --- | --- | --- | --- | --- |
| 10 to <20 | 69 | 8.2 (1.5) | -0.9 (1.2) | 38 | 8.1 (1.1) | -0.2 (0.8) |
| >20 | 100 | 8.1 (1.2) | -0.8 (1.0) | 45 | 7.8 (1.2) | -0.3 (0.7) |
| Race/ethnicity | | | | | | |
| White non-Hispanic | 125 | 8.0 (1.3) | -0.9 (1.0) | 65 | 7.9 (1.0) | -0.1 (0.7) |
| Other | 82 | 8.6 (1.4) | -1.0 (1.2) | 37 | 8.2 (1.3) | -0.6 (1.0) |
| Using a form of fixed dosing to calculate meal boluses (based on screening visit CRF) | | | | | | |
| Yes | 158 | 8.2 (1.4) | -0.9 (1.1) | 75 | 8.1 (1.0) | -0.3 (0.8) |
| No | 50 | 8.2 (1.3) | -1.0 (1.1) | 27 | 7.9 (1.4) | -0.4 (1.1) |
| C-peptide (nmol/L) | | | | | | |
| <0.8 | 108 | 8.3 (1.2) | -1.0 (1.1) | 46 | 8.3 (1.2) | -0.3 (0.9) |
| >0.8 | 100 | 8.2 (1.5) | -0.9(1.1) | 55 | 7.8 (1.0) | -0.3 (0.8) |
| Score on the subjective numeracy survey | | | | | | |
| <4.5 | 89 | 8.2 (1.3) | -0.9 (1.0) | 43 | 8.1 (1.2) | -0.3 (0.8) |
| >4.5 | 119 | 8.2 (1.5) | -1.0 (1.1) | 59 | 8.0 (1.1) | -0.3 (0.9) |
| Insulin modality prior to enrollment | | | | | | |
| MDI | 199 | 8.2 (1.4) | -0.9(1.1) | 98 | 8.0 (1.1) | -0.3 (0.9) |
| Pump | 9 | 8.1 (0.9) | -1.0 (0.9) | 4 | 8.2 (1.1) | -0.3 (0.3) |
| CGM user prior to enrollment | | | | | | |
| Yes | 141 | 8.1 (1.3) | -0.8 (1.0) | 77 | 7.9 (1.1) | -0.2 (0.6) |
| No | 67 | 8.5 (1.5) | -1.2 (1.2) | 25 | 8.5 (1.1) | -0.6 (1.3) |

Subgroup analysis of key secondary endpoint CGM metrics for the AID and CGM groups after 13 weeks support similar effects for CGM time in range (TIR; $70 - 180\mathrm{mg / dL}$ ), time below range (TBR; $&lt; 70\mathrm{mg / dL}$ ) and time above range (TAR; $&gt;180\mathrm{mg / dL}$ ) across the distribution of age, sex, racial or ethnic minorities, diabetes duration, baseline bolus method, and prior insulin regimen. The table below depicts percent of time within range and (SD). N values correspond to the baseline.

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Subgroup analysis of change in CGM metrics for AID group after 13 weeks

| | N | Time Below 70mg/dL | | Time in Range 70-180 mg/dL | | Time Above 180mg/dL | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Baseline mean % (SD) | Change from Baseline mean % (SD) | Baseline mean % (SD) | Change from Baseline mean % (SD) | Baseline mean % (SD) | Change from Baseline mean % (SD) |
| Overall | 214 | 0.7 (1.4) | -0.2 (1.2) | 48 (24) | 16 (19) | 51 (25) | -16 (19) |
| Baseline lab HbA1c | | | | | | | |
| <7.0% | 28 | 1.2 (2.3) | -0.5 (1.9) | 78 (15) | 3 (11) | 21 (15) | -2 (11) |
| 7.0% to <8.0% | 72 | 0.7 (1.4) | -0.3 (1.3) | 58 (18) | 10 (14) | 41 (18) | -9 (15) |
| 8.0% to <9.0% | 66 | 0.6 (1.4) | -0.2 (1.0) | 41 (18) | 21 (19) | 58 (19) | -21 (19) |
| ≥9.0% | 47 | 0.4 (0.9) | -0.1 (0.8) | 25 (18) | 27 (21) | 75 (18) | -27 (21) |
| Baseline time in range 70-180 mg/dL | | | | | | | |
| ≥60% | 79 | 1.2 (1.9) | -0.5 (1.7) | 74 (11) | 2 (9) | 25 (11) | -1 (10) |
| 30% to <60% | 80 | 0.6 (1.2) | -0.2 (0.9) | 45 (9) | 16 (14) | 54 (9) | -16 (14) |
| <30% | 55 | 0.1 (0.1) | 0.1 (0.3) | 16 (9) | 37 (15) | 84 (9) | -37 (15) |
| Non-insulin glucose lowering medications | | | | | | | |
| None | 46 | 0.7 (1.2) | -0.1 (1.2) | 41 (22) | 22 (17) | 59 (22) | -22 (18) |
| Other, but no SGLT-2i or GLP-1ra | 50 | 0.9 (1.9) | -0.4 (1.5) | 47 (24) | 17 (19) | 53 (25) | -17 (20) |
| GLP-1ra, but no SGLT-2i | 43 | 0.5 (1.3) | -0.2 (0.8) | 48 (26) | 13 (20) | 51 (27) | -13 (20) |
| SGLT-2i, but no GLP-1ra | 31 | 0.9 (1.9) | -0.6 (1.6) | 52 (24) | 11 (19) | 47 (25) | -10 (19) |

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| Both GLP-1ra and SGLT-2i | 44 | 0.4 (0.7) | 0.1 (0.7) | 55 (24) | 15 (18) | 45 (25) | -15 (18) |
| --- | --- | --- | --- | --- | --- | --- | --- |
| BMI (kg/m2) | | | | | | | |
| <30 | 59 | 0.7 (1.6) | -0.3 (1.4) | 47 (27) | 16 (21) | 53 (27) | -16 (22) |
| 30 to <35 | 72 | 0.7 (1.1) | -0.2 (1.1) | 48 (24) | 17 (19) | 51 (24) | -17 (19) |
| 35 to <40 | 34 | 0.7 (2.0) | -0.2 (1.4) | 49 (23) | 16 (18) | 50 (24) | -16 (18) |
| ≥40 | 49 | 0.6 (1.4) | -0.2 (1.1) | 50 (24) | 15 (16) | 50 (24) | -15 (16) |
| Total daily insulin (units/day) | | | | | | | |
| <100 | 128 | 0.6 (1.4) | -0.2 (1.2) | 46 (26) | 18 (20) | 54 (26) | -18 (21) |
| 100 to <150 | 57 | 0.8 (1.7) | -0.3 (1.3) | 52 (22) | 14 (16) | 48 (22) | -13 (16) |
| 150 to <200 | 15 | 0.6 (0.9) | -0.2 (0.7) | 48 (23) | 16 (17) | 52 (23) | -16 (17) |
| ≥200 | 14 | 0.9 (1.2) | -0.2 (0.9) | 58 (23) | 12 (15) | 41 (24) | -11 (16) |
| Sex | | | | | | | |
| Female | 105 | 0.5 (0.9) | -0.1 (1.0) | 46 (24) | 17 (18) | 53 (24) | -17 (19) |
| Male | 109 | 0.9 (1.8) | -0.4 (1.4) | 50 (25) | 16 (19) | 49 (25) | -15 (20) |
| Age at enrollment (years) | | | | | | | |
| <50 | 50 | 0.5 (1.2) | -0.2 (1.1) | 41 (26) | 22 (19) | 59 (27) | -22 (19) |
| 50 to <65 | 86 | 0.6 (1.4) | -0.2 (1.3) | 47 (25) | 16 (20) | 52 (26) | -16 (21) |
| ≥65 | 78 | 0.8 (1.6) | -0.2 (1.2) | 54 (21) | 12 (16) | 45 (21) | -12 (16) |
| Diabetes duration at enrollment (years) | | | | | | | |
| <5 | 11 | 1.0 (2.1) | -0.6 (1.8) | 41 (30) | 26 (19) | 58 (31) | -25 (20) |
| 5 to <10 | 31 | 0.6 (1.0) | -0.3 (0.8) | 45 (21) | 18 (17) | 54 (21) | -18 (18) |
| 10 to <20 | 71 | 0.7 (1.8) | -0.3 (1.5) | 47 (25) | 16 (20) | 52 (25) | -16 (20) |
| ≥20 | 101 | 0.6 (1.2) | -0.1 (1.0) | 50 (25) | 14 (18) | 49 (25) | -14 (19) |

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| Race/ethnicity | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| White non-Hispanic | 129 | 0.6 (1.3) | -0.2 (1.2) | 51 (26) | 16 (18) | 48 (26) | -16 (18) |
| Other | 84 | 0.8 (1.6) | -0.3 (1.3) | 43 (21) | 18 (20) | 56 (22) | -17 (20) |
| Using a form of fixed dosing to calculate meal boluses (based on screening visit CRF) | | | | | | | |
| Yes | 161 | 0.8 (1.6) | -0.3 (1.4) | 49 (24) | 15 (19) | 50 (25) | -15 (20) |
| No | 53 | 0.3 (0.6) | -0.0 (0.4) | 45 (24) | 20 (17) | 55 (25) | -20 (17) |
| C-peptide (nmol/L) | | | | | | | |
| <0.8 | 112 | 0.8 (1.4) | -0.3 (1.3) | 49 (23) | 14 (18) | 50 (23) | -14 (19) |
| ≥0.8 | 102 | 0.5 (1.5) | -0.2 (1.1) | 47 (26) | 18 (19) | 53 (27) | -18 (19) |
| Score on the subjective numeracy survey | | | | | | | |
| <4.5 | 91 | 0.7 (1.3) | -0.1 (1.1) | 49 (24) | 15 (19) | 51 (25) | -15 (19) |
| ≥4.5 | 123 | 0.7 (1.5) | -0.3 (1.2) | 48 (25) | 17 (19) | 52 (25) | -17 (19) |
| Insulin modality prior to enrollment | | | | | | | |
| MDI | 205 | 0.7 (1.5) | -0.2 (1.2) | 48 (24) | 16 (19) | 51 (25) | -16 (19) |
| Pump | 9 | 0.4 (0.8) | -0.1 (0.4) | 44 (24) | 21 (19) | 56 (24) | -20 (19) |
| CGM user prior to enrollment | | | | | | | |
| Yes | 146 | 0.6 (1.4) | -0.2 (1.2) | 48 (24) | 17 (17) | 52 (24) | -17 (18) |
| No | 68 | 0.8 (1.4) | -0.3 (1.3) | 49 (26) | 14 (22) | 50 (27) | -14 (22) |

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# Challenge Results

During this clinical study, subjects in the AID group participated in 3 meal challenges and 3 exercise challenges.

From the AID group 195 participants completed 567 meal challenges in which no bolus, half bolus or full bolus was delivered. Of the meal challenges 320 were lunch meals, 209 were dinner meals and 38 were meals outside of lunch or dinner. The median amount of carbohydrates was 60 grams. During and up to the 4 hours post the meal challenge the CGM time in range increased from 57% to 66% to 71% for no bolus, half bolus and full bolus respectively.

From the AID group 172 participants completed 511, 60-minute-long exercise challenges, of which 500 were intensity of mild or moderate. During and for 2 hours after the exercise challenge there was minimal (less than 0.01%) of time below 70 mg/dL as determined by CGM.

# Summary of Human Factors Validation Study

The study was conducted as established in K232382. No differences in critical tasks were identified between adults with type 1 diabetes (T1D) and adults with type 2 diabetes (T2D). A summative Human Factors validation was performed and followed FDA recognized standard IEC 62366-1 as well as the FDA guidance document *Applying Human Factors and Usability Engineering to Medical Devices* (February 3, 2016). A summative validation study evaluated a total of 30 individuals with T2D to ensure individuals can safely and effectively perform critical tasks associated with the use of Control-IQ+ technology.

# VII Proposed Labeling:

The labeling supports the finding of substantial equivalence for this device.

# VIII Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.