New Diabetes Innovations and Discoveries at 2019 ADA’s Scientific Sessions

This year’s American Diabetes Association Scientific Sessions didn’t disappoint with a great deal of research presented on diabetes medications, device development and other notable info about exercise management.

Here’s a quick summary:

AUTOMATED INSULIN DELIVERY SYSTEMS, HCL SYSTEMS & PUMP COMPONENTS

1. A new type of infusion set – Capillary Bio:  angled 13.5 mm set,
This set is a Steel-reinforced cannula meant to help prevent kinking. It has 4 “holes” for insulin to drip out with a flexible tube and appears to provide less inflammation to surrounding tissues with a larger insulin delivery area.

2. DIY HCL Outcomes  (university of Bern) Diabetes Center Berne
Using Open APS, Android APS, Loop with 80 DIY users with a collective 53 years data.

• • 77.5% in-range, 18% high, 4.5% low
  • +9.3% after switching to DIY  (similar daytime & nighttime)
  • -1.2% in low range
  • Reduction in daytime lows, not nighttime lows

3. 670G Experience – Dr. Lal, Stanford

• 79 patients (peds & adult) started on 670G, followed for 1 year
• Baseline A1c approx 8%, 60% time in –range
• Automode discontinuation was common and by 75% of the way through the study 44% had stopped using the system.
  • 3 mo 31%
  • 6 mo 40%
  • 9 mo 44%
• 12 mo 46%  (32% used it at least 70% of the time)
• Those who were more likely to discontinue use included younger age and those with a higher A1c with reasons including:  sensor (60%), supply issues (17%), fear of lows (10%), prefer MDI (7%), sports (7%)

4. Gen 3 iLet

• Dual-chamber with both Insulin & glucagon delivery
• To start the system only requires an entry of body weight entered and there is no run-in period or training provided
• If no CGM data is available the system delivers basal based on history and user boluses
• CGM used with the system includes both Dexcom G5 or Eversense
• The study with 34 adults w/T1, starting A1c <11, on either injections or pump therapy
• Target set to 120 on device
  • Mean (days 3-7):  162 (usual tx), 155 (ilet)
  • In-range (days 3-7): 62%, 70%  (significant)
  • Low (days 3-7): .6%, .6%
  • Overnight lows:  .4%, 0%
• Sensor MARD is greater w/Dexcom and time in low range was higher with Eversense

5. i-Let Insulin Only Bionic Panreas

• CGM system used includes dexcom G5 or Eversense CGM
• User only enters their weight with no run-in or training period
• Compared to mix of MDI/traditional pump users (iLet vs usual care):
  • Avg 155 vs 162 (no diff)
  • Time <54:  .7% vs .7%
  • Time <70:  2.8% vs 3.2% (nonsignificant)
  • Time in-range:  70% vs 61% (significant)
  • Overnight avg:  148 vs 163 (significant)
• Eversense users spent more time in hypoglycemia, perhaps d/t sensor differences

INNOVATIONS IN INSULIN THERAPY

Ultrarapid Lispro (URLi) improves post meal blood glucose

• Excipients:  Treprostinil (vasodilator), citrate (increases vascular permeability) helping to provide a 10-min earlier onset with 3-fold increased action in first 30 minutes.
• 43% less exposure after 3 hrs
• Studied were done in adults with T1D & T2D.  3 groups:  mealtime URLi, mealtime humalog, 20-min post meal use of Urli. Findings included:
  • A1c of post meal URLi group ended up .2 higher than other groups
  • No change/difference in total insulin doses, basal or bolus
  • Post meal excursion with URLi was about 30 points lower compared to Humalog with no diff with 20-min post meal URLi
  • No differences in hypoglycemia rates, except at >4 hrs Post meal (less hypo for mealtime URli, none for 20min postmeal URLi)
  • A negative to use is that there appeared to be more injection site reactions with URLi.

Glargine u300 vs. Degludec

• Impaired kidney function present in >20% of T2s, risk factor for hypoglycemia due to reduced insulin clearance
• As eGFR increases, benefit of Gla-300 over Ideg increases (particularly at eGFR <60). 
• A1c reduction is 0.4 greater
• Fingerstick glucose is lower
• No change in hypoglycemia risk

ROAD TO THE ARTIFICIAL PANCREAS

Everyone is racing to have the best artificial pancreas for people with diabetes to use.

The overview of those that are in the works include:

International Diabetes Closed Loop (Tandem Control IQ)

• Study at University of Virginia
• 6 month randomized multicenter controlled trial, Tandem X2, Dexcom G6
• Sensor-augmented pump vs. Control IQ closed loop
• The system includes automated correction boluses in addition to basal modulation and Hypo prevention system
• Gradual intensification of overnight control to slowly move to a target of 110-120 fasting
• Study included 168 participants, Ages 14+, no restriction based on previous mgt, control, severe lows
• All statistically significant outcomes:
  • TIR  59% vs 71%, results achieved immediately & maintained (nighttime TIR 59% vs 76%)
  • Those w/A1c <6.5 at baseline, achieved 85% TIR.
  • Mean  166 vs. 156
  • A1c  7.39 vs. 7.06
  • Time <70  1.93% vs 1.40%
  • Time < 54  .24% vs. .21%
• 97% CGM use; avg .21 fingersticks per day
• 92% of time in closed loop mode
• No severe lows occurred
• Ease of use score 4.7/5; desire to continue use 4.8/5
• Meal announcement still required
• Users CAN extend boluses
• Uses the user’s preferred basal profile as the starting point
• Potential launch:  4^th qtr 2019

Use of control IQ in children

• More glucose variance among kids age 7-12 than any other age group
• Best outcomes when used 24/7, not just at night.
• 82% of time in-range overnight, 2% low.
• Time <70:  3.9% vs 2.8%
• TIR 59% vs 71%

Horizon (OmniPod HCL) – Stanford

• Uses standard smartphone (app-based)
• 73% time in-range
• Algorithm updates regularly based on previous data
• “Hybrid” basal rates – similar to but not exactly the same as user’s previous settings
• Meals must be announced
• Potential launch date:  3^rd-4^th qtr 2020

Medtronic announcements

      * Partnership with Tidepool announced. Goal is to develop and “interoperable automated insulin pump for managing diabetes”

      * New trials – “Bluetooth Enabled MiniMed(TM) 780G Advanced Hybrid Closed Loop System Designed to Automate Correction Bolusing”

             – “Pivotal Trial for Next-Generation Guardian(TM) Continuous Glucose Monitoring Sensor”.

INTEROPERABLE HCL COMPONENTS

CGM Must meet the following criteria:

• >87% of all values within 20% of YSi
• >80% within 15% of YSi when above 180 AND no values < 70
• >70% within 15% of YSi when 70-180
• >85% within 15 mg/dl when below 70 AND no values >180
• Similar performance in adults & peds required
• ROC accuracy guidelines also established
• No clinically significant data gaps allowed

EXERCISE

Dual-hormone (insulin with glucagon) HCL

• Castle et al, Diabetes Care Vol 41, July 2018
• Achieved best control during and after 45min of exercise compared to use of single-hormone HCL and open-loop
• Incidence of lows:  3.4% (dual hormone); 8.3% (single hormone HCL); 7.6% (PLGS)

Fasting vs PM exercise

• Jane Yardley, University of Alberta
• 10 adult participants
• 24 min HIIT session (Twelve 10-sec sprints) plus 10 min warmup, 11 min cool down
• Fasting (7am):  rose 32 mg/dl (1.8 mmol) during exercise, rose another 7mg/dl (0.4mmol) 1 hr later
• Afternoon (5pm) 1 hr after glucerna bar:  fell 7mg/dl (.4 mmol during), another 21mg/dl (1.2mmol)  1 hr later
• (p= .039 1h post)

Does daily activity or exercise affect insulin sensitivity more? (poster)

• Mano et al, Kyoto University, Japan
• In people with lower BMI (<23), exercise habits (to “sweating point”) correlated most strongly with reduced insulin resistance.
• In people with higher BMI (?23), non-exercise activity (walking at least 1hr/day) correlated most strongly with reduced insulin resistance.

Benefits of exercise frequency in T1D (poster)

• Ridell Mike, York University, Toronto
• Type1 Diabetes Exercise Initiative Pilot Study
• 33 Adults w/T1, exercising at least 30 minutes, with a mix of aerobic, resistance & interval training, twice weekly.
• 24-hr period from start of exercise:  TIR 57%; non-exercise days:  TIR 48%.  No differences based on exercise type.  Time above 180 33% on exercise days vs 44% on non-exercise days.  Time below 70:  4.5% on exercise days  vs 3.8% on non-exercise days.
• Difference between groups started to fade 16-20 hours after the exercise sessions.