Table 1: Dual hormone studies published between 2010–2019.
Study characteristics and results for the twenty dual hormone studies reviewed.
| Participant Characteristics | ||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Author (ref) | Date of Online Publication | Location of Research Group | Number of participants | Mean age (years) | Mean DM Duration (years) | Mean A1c (%) | Duration | Study design | Treatment group(s) | Control group | Location | Standarized Exercise | Components | Monitoring | First Author (ref) | AID Initialization | AID Algorithm | Meals Announced? | Glucagon Delivery Strategy | Glucagon Delivered (SD) | Mean Glucose mg/dl (SD) | Time in Range 70–180mg/dl (SD) | Time in Hypoglycemia <70md/dl (SD) | Time in Hyperglycemia >180mg/dl (SD) | Hypoglycemia Treatments Per Day | Adverse Events | ||||||
| El-Khatib et al. (35) | 4/16/2010 | Boston, MA | 11 adults | 40 | 23 | 7.3 | 27 hours | Non-randomized | DH | No control group | Inpatient | No | Computer, Deltec Cozmo pumps, venous blood glucose samples, manual entry of rates | Onsite | El-Khatib et al. (35) | Weight only | Model preditive control | No meal annoucement allowed | Proportional derivative control to prevent <100mg/dl | 1.70mcg/kg/day | 164 (SD 17) | 62% | <1% | 38% | 0 | No nausea or vomitting with glucagon | ||||||
| Russell et al. (50) | 8/28/2012 | Boston, MA | 6 adults | 52 | 32 | 7.4 | 51 hours | Non-randomized | DH | No control group | Inpatient | No | OmniPod pumps, Navigator CGM | Onsite | Russell et al. (50) | Weight only | Model preditive control | Yes | Proportional derivative control to prevent <100mg/dl | 3.6mcg/kg/day (5.1) | 158 (SD 44) | 68% (SD 12) | 0.7% (0.8) | 31% (12) | 3.2g/kg/day (0.3) | Subject who received highest amount of glucagon | ||||||
| El-Khatib et al. (51) | 2/4/2014 | Boston, MA | 12 adults/12 adolescents | 45/15 | 27/7 | 7.3/7.9 | 48 hours | Randomized | meal prime, WO meal prime | No control group | Inpatient | Yes | OmniPod pumps, Navigator CGM | Onsite | El-Khatib et al. (51) | Weight only | Model preditive control | Yes | Proportional derivative control to prevent <100mg/dl | WMP 6.8mcg/kg/day (2.5); WOMP 6.6mcg/kg/day (3.5) | WMP 132 (9); WOMP 146 (9) | 0.03 | WMP 80%; WOMP 70% | 0.04 | WMP 5.1%; WOMP 3.6% | 0.7 | Not reported | 0.92/day | Two subjects reported nausea. | |||
| Russell et al. (34) | 6/17/2014 | Boston, MA | 20 adults/32 adolescents | 40/16 | 24/9 | 7.1/8.2 | 5 days | Randomized, crossover | DH | Usual care with pump or SAP (45% own sensor use) | Adults: Hotel, Adolescents: Diabetes camp | No | Iphone 4S, G4 Dexcom, Tslim pumps M5 | Onsite | Russell et al. (34) | Weight only | Model preditive control | Recommended but not required | Proportional derivative control to prevent <100mg/dl | 0.82mg/day (0.41) | Adults DH 133 (13), control 159 (30.4) | <0.001 | Adults DH 79.5% (8.3), control 58.8% (14.6) | <0.001 | Adults DH 4.1% (3.5), control 7.3% (4.7) | 0.01 | Adults DH 16.5% (1.8), control 33.8% (16.4) | <0.001 | Adults DH:2.2 (3.2), control 3.4 (3.1) | 0.15 | One patient reported nausea, two reported one episode of vomitting. | |
| Russell et al. (40) | 2/7/2016 | Boston, MA | 19 children | 9.8 | 5 | 7.8 | 5 days | Randomized, crossover | DH | Usual care with pump or SAP | Diabetes camp | No | Iphone 4S, G4 Dexcom, Tslim pumps | Onsite | Russell et al. (40) | Weight only | Model preditive control | Recommended but not required | Proportional derivative control to prevent <100mg/dl | 10.9 μg/kg/day(4.0) | DH 136.8 (10.8), control 167 (30.6) | <0.001 | DH: 80.6% (7.4), control 57.6% (14) | (< 60) DH: 1.2% (1.1), control: 2.8% (1.2) | <0.001 | DH 16% (6.4), control 36.3% (15.7) | <0.001 | events/participant/study: DH 3, control 5 | 0.037 | No difference in nausea rates DH vs. control. | ||
| El-Khatib et al. (41) | 12/23/2016 | Boston, MA; Worcester, MA; Palo Alto, CA; Chapel Hill, NC | 43 adults | 33.3 | 16.9 | 7.7 | 11 days | Randomized, crossover | DH | Usual care with pump or SAP (59% own sensor use) | Home | No | Iphone 4S, G4 Dexcom, Tslim pumps | Remote | El-Khatib et al. (41) | Weight only | Model preditive control | Recommended but not required | Proportional derivative control to prevent <100mg/dl | 6.8 μg/kg/day | DH 140.4 (10.8), control 162 (28.8) | <0.001 | DH 78.4% (6.0), Control 61.9% (14.4) | <0.001 | (<60) DH 0.6% (0.6), control 1.9% (1.7) | <0.001 | DH 19.8% (6.1), control 33.6% (16.4) | <0.001 | DH 0.4 (0.3), control 0.9 (0.7) | <0.001 | 21 reported nausea with DH. 5 reported nuasea in control. | |
| Haidar et al. (43) | 1/30/2013 | Montreal, Canada | 15 adults | 47.1 | 26.5 | 7.9 | 15 hours | Randomized, crossover | DH | SAP | Inpatient | Yes | Minimed veo pumps, Sofsensor Medtronic, manual entry of rates | Onsite | Haidar et al. (43) | Weight, TDD, ICR | Model predictive control | Yes | Logical rules based on glucose value and trend | 0.076mg/visit | Dh 140.4, control 142.2 | 0.74 | DH 70.7%, control 57.3% | 0.003 | DH 0%, control 10.2% | 0.01 | DH 29.3%, control 25.6% | 0.74 | At least one event per study: DH 7%, control 53% | 0.02 | None other than hypoglycemia | |
| Haidar et al. (30) | 12/2/2014 | Montreal, Canada | 20 adults/10 adolescents | 43/14 | 16/8 | 7.7/7.9 | 24 hours | Randomized, crossover | SH, DH | Usual care with pump | Inpatient | Yes | Minimed veo pumps, Sofsensor Medtronic, manual entry of rates | Onsite | Haidar et al. (30) | Weight, TDD, ICR | Model predictive control | Yes | Logical rules based on glucose value and trend | 2.0 μg/kg/vist | DH 135 (34), SH 126 (27), control 144 (59.4) | DH:C 0.26 | DH 63% (18), SH 62% (18), control 51% (19 | DH:C <0.001 | DH 1.5%, SH 3.1%, control 13.3% | DH:C <0.001 | DH 20% (15), SH 20% (16), control 26% (22) | DH:C 0.83 | At least one event per study: DH 21%, SH 17%, control 83% | DH:C <0.001 | Not reported | |
| Haidar et al. (44) | 6/13/2015 | Montreal, Canada | 33 children | 13.3 | 7.5 | 8.3 | 3 nights | Randomized, crossover | SH, DH | Usual care with pump | Diabetes camp | No | G4 dexcom, Accu-check combo pumps, tablet computer, manually entry of rates | Remote | Haidar et al. (44) | Weight, TDD, ICR | Model predictive control | N/A | Logical rules based on glucose value and trend | 0.7μg/kg/night (1.0) | DH 138.6 (30.6), SH 145.8 (30.6), control 167 (25) | DH:C <0.001 | DH 84%, SH 77%, control 54% | DH:C <0.001 | DH 0%, SH 3.1%, control 3.4% | DH:C <0.001 | DH 13%, SH 20%, control 38% | DH:C <0.001 | events/night: DH 0, SH 0.04, C 0.15 | Not reported | ||
| Haidar et al.(45) | 11/3/2015 | Montreal, Canada | 21 adults/7 adolescents | 39/15 | 21/8 | 7.4/7.7 | 2 nights | Randomized, crossover | SH, DH | Usual care with pump | Home | Yes | Paradigm veo pump, Enlite sensor, manual entry of rates | Onsite | Haidar et al.(45) | Weight, TDD, ICR | Model predictive control | Yes | Logical rules based on glucose value and trend | 0.4μg/kg/night | DH 111.6 (28.8), SH 111.6 (30.6), control 120.6 (43) | DH:C 0.57 | DH 93%, SH 91%, control 70% | DH:C <0.001 | DH 1%, SH 5%, control 14% | DH:C <0.001 | DH 0%, SH 0%, control 4% | DH:C 0.66 | total events: DH3 SH 6, control 14, | Not reported | ||
| Gingras et al.(46) | 6/15/2015 | Montreal, Canada | 12 adults | 51.3 | 32.6 | 7.4 | 14 hours | Randomized, crossover | DH with ICR prandial dose, DH with qualitative prandial dose | Usual care with pump | Inpatient | No | Accu-check combo pump, Enlite Medtronic sensor, manual entry of rates | Onsite | Gingras et al.(46) | Weight, TDD, ICR | Model predictive control | Yes | Logical rules based on glucose value and trend | ICR 0.044mg/study, Qualitative 0.042mg/study | ICR 147.6 (37.8), Qualitative 151.2 (30.6), control 172.8 (36) | ICR:C 0.03 | ICR 66.8%, Qualitative 64.2%, control 49.9% | ICR:C 0.10 | ICR 0.1%, Qualitative 5.4%, control 5.6% | ICR:C 0.81 | ICR 20.7%, Qualitative 29.3%, control 40.5% | ICR:C 0.03 | Not reported | Not reported | ||
| Taleb et al. (12) | 10/6/2016 | Montreal, Canada | 17 adults | 37.2 | 23.1 | 8 | 90 minutes | Randomized, crossover | DH/SH with Continuous exercise, DH/SH with Interval exercise | No control group | Inpatient | Yes | Computer, Dexcom G4 sensor, MiniMed Paradigm Veo, manual entry of rates | Onsite | Taleb et al. (12) | Weight, TDD, ICR | Model predictive control | N/A | Logical rules based on glucose value and trend | DH Continuous 0.126mg/study (0.057), DH Interval | Not reported | DH Cont 100%, SH Cont 68.1%; DH Interval 100%, SH Interval 72.5% | Cont: 0.004 Interval: 0.11 | DH Cont 0%, SH Cont 22.5%; DH Interval 0%, SH Interval 0% | Cont: 0.07 Interval: 0.04 | Not reported | total events: DH Cont 2, SH Cont 4, DH Interval 1, SH Interval 6 | Not reported | ||||
| Haidar et al.(38) | 1/18/2017 | Montreal, Canada | 23 adults | 41 | 24 | 7.5 | 60 hours | Randomized, crossover | SH, DH | Usual care with SAP | Home | No | Dexcom G4, Sensewear, Accu-check combo pumps, manual entry of rates | Onsite | Haidar et al.(38) | Weight, TDD, ICR | Model predictive control | Yes | Logical rules based on glucose value and trend | 7.9 μg/kg/study (4.1) | DH 142.2 (50.4), SH 142.2 (50.4), control 135 (54) | DH:C 0.16 | DH 79%, SH 75%, control 64% | DH:C 0.31 | DH 3.6%, SH 3.9%, control 7.9% | DH:C 0.002 | DH 16%, SH 20%, control 15% | DH:C 0.13 | total events: DH 6, SH 14, control 34 | Not reported | ||
| Castle et al.(39) | 3/23/2010 | Portland, OR | 14 adults | 36.7 | 14.1 | 7.6 | 28 hours | Randomized | Low gain, high gain glucagon delivery | Placebo delivery | Inpatient | No | Insulin via animas IR 1000 pump, glucagon via medfusion 2001 syringe pump, manual entry of rates | Onsite | Castle et al. (39) | TDD, BMI, Age | Fading memory proportional derivative | Yes | High gain, low gain | low gain: 0.746mg/day (134) vs. high gain 0.516mg/day | High gain: 138 (SD 17); Low gain: 157 (SD 24) placebo 135 (SD 16) | Numbers not reported | NS | DH 1.04%, control 2.77% | DH:C 0.04 | Numbers not reported | NS | DH 1.1/study (0.5), control 3.9/study (1) | 0.01 | One subject reported nausea with during DH | ||
| Jacobs et al.(29) | 6/24/2016 | Portland, OR | 21 adults | 32 | 15.4 | 7.5 | 22 hours | Randomized, crossover | APX with exercise adjustment, APN with no exercise adjustment | Usual care with SAP | Inpatient | Yes | Google nexus smartphone, tslim pumps, dexcom G4 | Onsite | Jacobs et al.(29) | TDD, BMI, Age | Proportional derivative | Yes | Reduced insulin and increased glucagon for exercise | APX 3.6μg/kg, APN 2.8μg/kg | APX 154.8, APN 145.8, control 154.8 | APX:APN 0.032 | APX 75%, APN 81%, control 72% | APX:APN 0.11 | APX 0.3%, APN 3.1%, control 0.8% | APX:APN 0.001 | APX 25%, APN 17%, control 27% | APX:APN 0.09 | total events: APX 6, APN 9, control 7 | APX:APN 0.08 | Not reported | |
| Castle et al.(28) | 5/13/2018 | Portland, OR | 20 adults | 34.5 | 20.2 | 7.5 | 4 days | Randomized, crossover | SH, DH, PLGS, CC | Usual care with pump or SAP (65% own sensor use) | Outpatient | Yes | Google nexus smartphone, tslim pumps, dexcom G5 | Remote | Castle et al.(28) | TDD, BMI, Age | Fading memory proportional derivative | Yes | Reduced insulin and increased glucagon for exercise | 0.510 mg/day (0.207) | DH 149 (38), SH 145 (31), PLGS 170 (49), control 164 (62) | DH:C 0.29 | DH 72.0 (10.8), SH 74.3 (8.0), PLGS 65.2 (13.5), control 63.1 (17.3) | DH:C 0.010 | DH 1.3 (1.0), SH 2.8 (1.7), PLGS 2.0 (1.5), control 3.1 (3.2) | DH:C 0.007 | DH 26.7 (11.3), SH 22.9 (8.7), PLGS 32.8 (13.9), control 33.7(18.1) | DH:C 0.054 | per day: DH 0.8 (0.7), SH 1.7 (1.4), PLGS 1.3 (1.3), control 1.5 (1.2) | DH:C 0.010 | GI upset in 23% of DH, 0% SH, 13% PLGS, 5% control | |
| Von Bon et al.(48) | 10/16/2012 | Amsterdam, The Netherlands | 10 adults | 55.4 | 34.6 | 8 | 8 hours | Non-randomized | DH | Usual care with pump | Inpatient | Yes | Computer, System gold medtronic minimed sensor, D-tron+ pumps, Polar HR monitor | Onsite | Von Bon et al.(48) | TDD | Proportional derivative control | No | Glucagon given if <117, bolus size based rate of fall of glucose | postbreakfast 0.04 mg, postexercise 0.12mg, postlunch 0.07mg | DH 156.6, control 162 | DH:C 0.74 | DH 62.3%, control 61.2% | DH:C 0.78 | DH 5.3%, control 4.1% | DH:C 0.60 | DH 32.4%, control 34.7% | DH:C 0.54 | events: DH 4, control 2 | Not reported | ||
| Von Bon et al.(36) | 11/15/2013 | Amsterdam, The Netherlands | 16 adults | 52.1 | 35.3 | 7.6 | 48 hours | Non-randomized | DH | Usual care with pump | Home | Yes | Computer, Sofsensor or Enlite medtronic minimed sensor, D-tron+ pumps | Onsite | Von Bon et al.(36) | TDD | Proportional derivative control | No | Glucagon given if <117, bolus size based rate of fall of glucose | Daytime 1.7–2.7mg, Nighttime 0.6mg | Day 2 median: DH 7.70 (2.29), control 8.84 (0.87) | DH:C 0.0273 | Day 2 median: DH 76.5% (23.9%), control 66.0% (29.8%) | DH:C 0.1618 | Day 2 median: DH 2.8% (9.8%), control 0.0% (11.1%) | DH:C 0.0172 | Day 2 median: DH 18.3% (20.0%), control 31.0% (29.8%) | DH:C 0.0889 | events: DH 6, control 6 | Not reported | ||
| Blauw et al.(49) | 3/22/2016 | Amsterdam, The Netherlands | 16 adults | 41 | 18 | 7.7 | 4 days | Randomized, crossover | DH | Usual care with pump | Inpatient then Home | No | Inreda DiabeticBV(contains CGM, control algorithm, insulin pump glucagon pump), Enlite medtronic sensors | Onsite/Remote | Blauw et al.(49) | Weight only | Proportional derivative control | No | Triggered by glucose threshold | 0.74mg/study | DH 133.2, control 145.8 | DH:C 0.059 | DH 84.7%, control 68.5% | DH:C 0.007 | DH 1.3%, control 2.4% | DH:C 0.139 | DH 11.9%, control 24.3% | DH:C 0.022 | events: DH 12, control 21 | One subject with nausea after 0.88mg glucagon, 6 glucagon infusion set occlusions | ||
| Abitbol et al.(31) | 2/3/2018 | Toronto, Canada | 18 adults with hypo unaware, 17 adults hypo aware | 45.6 | 26.9 | 7.7 | 11 hours overnight | Randomized, crossover | DH | SH | Inpatient | No | Enlite sensor, Minimed Veo pump, manual entry of rates | Onsite | Abitbol et al.(31) | TDD, ICR | Model predictive control | Yes | Logical rules based on glucose value and trend | Not reported | DH 122.4 (19.8), SH 142.2 (23.4) | DH:SH 0.01 | DH 100%, SH 77% | DH:SH 0.04 | Not reported | DH 0%, SH 17% | DH:SH 0.04 | Hypo unaware: 0.38 events/night, Hypo aware 0.25 events/night | Not reported | |||