Welcome to the ATTD 2022 Interactive Program

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Displaying One Session

Session Type
Oral Presentations Session
Date
Thu, 28.04.2022
Session Time
16:40 - 18:10
Room
Hall 118

EFFECT OF TIRZEPATIDE VERSUS INSULIN DEGLUDEC ON GLYCEMIC CONTROL CAPTURED WITH CONTINUOUS GLUCOSE MONITORING IN PATIENTS WITH TYPE 2 DIABETES (SURPASS-3 CGM)

Session Type
Oral Presentations Session
Date
Thu, 28.04.2022
Session Time
16:40 - 18:10
Room
Hall 118
Lecture Time
16:40 - 16:48

Abstract

Background and Aims

To evaluate the effects of tirzepatide, a dual GIP/GLP-1 receptor agonist, vs insulin degludec (IDeg) on glycaemic control captured with continuous glucose monitoring (CGM) over 24 hours in a subpopulation of participants in the SURPASS-3 trial.

Methods

Insulin-naive participants with type 2 diabetes treated with metformin with/without sodium-glucose co-transporter-2 inhibitors (SGLT-2i) were randomized (1:1:1:1) to once-weekly tirzepatide (5, 10, 15 mg) or once-daily IDeg. Interstitial glucose values were collected by CGM at 5-minute intervals for 7-10 days at baseline, week 24 (Wk24) and week 52 (Wk52). Primary outcome was percentage of time in tight range (TITR) (3.9-7.8 mmol/L) during a 24-hour period for pooled tirzepatide 10mg/15mg compared to IDeg at Wk52. Secondary outcomes included comparing tirzepatide vs IDeg for the percentage of time in range (TIR), time below range (TBR) <3.9 mmol/L, and coefficient of variation (CV) at Wk52.

Results

In the tirzepatide (5 mg N=64, 10 mg N=51, 15 mg N=73) and IDeg (N=55) groups, overall mean baseline HbA1c was 8.14% and fasting serum glucose was 9.40 mmol/L. Pooled tirzepatide 10 mg/15 mg spent significantly more TITR than IDeg at Wk52 (72.60 ± 2.45% vs 48.04 ± 3.74% p<0.001). The percentage of TBR ≤3.9 mmol/L at Wk52 was significantly lower for all doses of tirzepatide vs IDeg. Tirzepatide significantly reduced the Within-day CV vs IDeg at Wk52. No significant differences were observed based on SGLT-2i utilization.

Conclusions

Tirzepatide demonstrated superior glycaemic control and decreased glycaemic variability measured using CGM with lower risk of hypoglycaemia in comparison to insulin degludec.

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AUTOMATED INSULIN DELIVERY (AID)-ENHANCED WITH SGLT2I AS COMBINED THERAPY IN TYPE 1 DIABETES

Session Type
Oral Presentations Session
Date
Thu, 28.04.2022
Session Time
16:40 - 18:10
Room
Hall 118
Lecture Time
16:48 - 16:56

Abstract

Background and Aims

Use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) as adjunct therapy to insulin in type 1 diabetes (T1D) has been previously studied. Here we present data from the first free-living trial combining low-dose SGLT2i with commercial automated insulin delivery (AID) or predictive low glucose suspend (PLGS) systems.

Methods

In an eight-week, randomized, controlled, crossover trial, adults with T1D received 5 mg/day empagliflozin (EMPA) or no drug (NOEMPA) as adjunct to insulin therapy. Participants were also randomized to sequential orders of AID (Control-IQ) and PLGS (Basal-IQ) systems for four and two weeks, respectively. The primary endpoint was percent time-in-range (TIR) 3·9-10mmol/L during daytime (7:00-23:00h) while on AID (NCT04201496).

Results

39 subjects were enrolled, 35 were randomized, 34 (EMPA; n=18 and NOEMPA n=16) were analyzed with intention-to-treat intention (IIT), 32 (EMPA; n=16 and NOEMPA n=16) completed the trial. On AID, EMPA vs. NOEMPA had higher daytime TIR 81% vs. 71% with a mean estimated difference of +9·9% [95%CI 0.6 to 19.1];p=0.04. On PLGS, the EMPA vs NOEMPA daytime TIR was 80% vs. 63%, mean estimated difference of +16.5%[95% CI 7.3, 25.7];p<0.001. One subject on SGLT2i and AID had mild diabetic ketoacidosis that was precipitated by non-functioning insulin pump infusion site blockage.

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Conclusions

In an eight-week outpatient study, the addition of 5 mg daily empagliflozin to commercially available AID or PLGS systems significantly improved daytime glucose control in individuals with T1D, without increased hypoglycemia risk. These promising results warrant further evaluation in large-scale clinical trials.

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ACHIEVEMENT OF HBA1C LESS THAN 5.7% WITHOUT WEIGHT GAIN AND HYPOGLYCEMIA IN PEOPLE WITH T2D TREATED WITH TIRZEPATIDE ACROSS THE PHASE 3 SURPASS PROGRAM

Session Type
Oral Presentations Session
Date
Thu, 28.04.2022
Session Time
16:40 - 18:10
Room
Hall 118
Lecture Time
16:56 - 17:04

Abstract

Background and Aims

Tirzepatide, a novel dual GIP/GLP-1 receptor agonist developed for type 2 diabetes treatment, provided greater HbA1c and body weight reductions compared with placebo and active comparators with 23% to 62% of tirzepatide-treated participants achieving a HbA1c <5.7% in the phase 3 SURPASS studies. This post-hoc analysis evaluated the proportion of participants who achieved a HbA1c <5.7% without weight gain and hypoglycemia in these studies.

Methods

We compared the proportion of participants achieving the triple endpoint between the tirzepatide (5, 10, or 15 mg) and respective comparator groups using the efficacy analysis dataset without rescue medication. End of treatment HbA1c and weight were evaluated at week 40 (SURPASS-1, 2, 5) and week 52 (SURPASS-3, 4). Hypoglycemia included blood glucose level <54 mg/dL with symptoms of hypoglycemia or severe hypoglycemia.

Results

More participants treated with any dose of tirzepatide achieved the triple endpoint compared to placebo or active comparators in SURPASS 1-5 (Figure). Tirzepatide 15mg led to 51%, 50%, 48%, 42%, 56% (in SURPASS 1-5, respectively) of participants reaching the triple endpoint, compared to 1% with placebo (SURPASS 1), 18% with semaglutide 1mg (SURPASS 2), 4% with degludec (SURPASS 3), 2% with glargine U100 (SURPASS 4), and 3% with placebo (SURPASS 5).

Conclusions

Significantly more participants treated with tirzepatide achieved normoglycemia without weight gain and hypoglycemia compared to placebo, semaglutide 1 mg, or basal insulin. Up to 56% of the participants treated with tirzepatide 15 mg achieved this triple endpoint.

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T1DM REMISSION AND Β-CELL REGENERATION, INDUCED BY ORAL ADMINISTRATION OF TRIPLE-DRUG COMBINATION OF DPP-4 INHIBITOR, PPI, AND GABA IN NOD MICE. A PROOF-OF-CONCEPT

Session Type
Oral Presentations Session
Date
Thu, 28.04.2022
Session Time
16:40 - 18:10
Room
Hall 118
Lecture Time
17:04 - 17:12

Abstract

Background and Aims

Our concept views T1DM as an immune-triggered neurodegenerative disorder of the endocrine pancreas. Our previous pilot studies in adults have shown that with triple therapy (TT) insulin demands were reduced by 59%, in parallel with a significant reduction of HBA1C and without weight loss. 31.6% of participants entered a long-term remission and became insulin-free.

Methods

We studied 150 NOD mice for a total of 268 days, including the observation period, two main experiments which lasted 70 days and included the treatment arm, prevention arm and crossover. After 99 days (supervision), 51 animals became diabetic and were randomly assigned to five groups: ABC; AB; AC; BC, and Placebo (A - GABA; B – Sitagliptin; C – Omeprazole).

Results

The ABC group demonstrated the best effect compared to other combinations. On day 71 the ABC vs Placebo groups showed: Blood Glucose (BG) 15.7 ± 7.7 and 27.3 ± 10.2 nmol/l (p=0.036); C-peptide 0.96 ± 0.54 and 0.42 ± 0.77 nmol/l (p= 0.022); insulin 7.09±2.72 and 3.20±3.27 nmol/l (p=0.018); Insulin/Glucagon ratio 0.19 ± 0.07 and 0.09± 0.09 (p=0.021); exogenous insulin demands 0.3 ± 0.9 and 1.8 ± 1.4 units/mice (p=0.009) respectively. Immunohistochemistry analysis demonstrated the elevated number of insulin – producing cells in ABC group when compared to Placebo.

Conclusions

TT has resulted in significant improvement in the clinical, laboratory, and morphological parameters in NOD mice. 55% of animals in the ABC group have entered remission. All-in-all this study is proof of concept and efficacy of the new T1DM treatment approach.

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AT278 (U500) – PK/PD AND SAFETY OF RAPID-ACTING CONCENTRATED INSULIN ASPART

Session Type
Oral Presentations Session
Date
Thu, 28.04.2022
Session Time
16:40 - 18:10
Room
Hall 118
Lecture Time
17:12 - 17:20

Abstract

Background and Aims

Concentrated insulins allow administration of high insulin doses in a smaller volume. This enables a reduction in the number of injections for people with diabetes with high insulin needs and supports miniaturisation of insulin delivery devices. PK/PD and safety of a new concentrated insulin aspart formulation (AT278 U500/ml) were evaluated and compared with that of standard insulin aspart (IAsp U100/ml).

Methods

Serum insulin aspart and plasma glucose were measured in 38 adult male subjects with type 1 diabetes following a single s.c. dose (0.3 U/kg) of insulins in a randomised, double-blind, crossover, euglycaemic clamp study.

Results

AT278 showed a faster onset of insulin exposure compared with IAsp, as demonstrated by an earlier onset of appearance (-6.5 min, P<0.0001), earlier tEarly50%Cmax (-23.0 min, P<0.0001), and 4.0 times higher AUCInsulin,0-30min (95% CI: 3.29; 4.90). AT278 showed a more rapid onset of glucose-lowering effect compared with IAsp, as demonstrated by an earlier onset of action (-9.5 min, P<0.0001) and earlier tEarly50%GIRmax (-20.0 min, P<0.0001). Overall insulin exposure and glucose-lowering effect were comparable between both insulins (AUCInsulin,0-8h treatment ratio 0.98 [95% CI: 0.92; 1.00]; AUCGIR,0-8h treatment ratio 1.02 [95% CI: 0.95; 1.09]). All reported adverse events were mild in intensity and no safety signals were detected.

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Conclusions

Concentrated insulin aspart AT278 maintains the rapid-acting characteristics in a reduced dose volume. It has the potential to improve blood glucose management and convenience for people on high-dose insulin therapy and to match the demands of next generation insulin delivery devices with smaller reservoirs.

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PREVENTION OF T1DM, INDUCED BY ORAL ADMINISTRATION OF TRIPLE-DRUG COMBINATION OF DPP-4 INHIBITOR, PPI, AND GABA IN NOD MICE. A PROOF-OF-CONCEPT

Session Type
Oral Presentations Session
Date
Thu, 28.04.2022
Session Time
16:40 - 18:10
Room
Hall 118
Lecture Time
17:20 - 17:28

Abstract

Background and Aims

T1DM prevention remains the challenge. Studies dedicated to this issue are almost exclusively aimed at the immune system; the results are mainly disappointing or insufficient to draw definite conclusions. Our concept views T1DM as an immune-triggered neurodegenerative disorder of the endocrine pancreas. Our previous studies in NOD mice and humans have shown the effectiveness of triple therapy (TT) in β-cell preservation and regeneration.

Methods

We studied 150 NOD mice for a total of 268 days. After 99 days of the supervision period, the 94 animals who remained healthy were randomly assigned to five groups: ABC; AB; AC; BC, and Placebo (A - GABA; B – Sitagliptin; C – Omeprazole). The duration of the study was 70 days

Results

The ABC group demonstrated the best effect compared to other combinations. On day 71, the average metrics of ABC vs Placebo groups showed: Number of mice who remained healthy:17 vs. 9 (p=0.004); Blood Glucose (BG) 9.9±6.2 vs. 19.0±7.8 mmol/l (p=0.001); C-peptide 1.8 ± 0.3 vs. 0.8 ± 0.7 nmol/l; Glucose/insulin ratio 1.2 ± 1.6 vs. 5.5 ± 5.5 (p= 0.001); Glucose/C-peptide ratio 6.3 ± 7.7 vs. 112.1 ± 193.3 respectively (p=0.001); The prevention rate of the onset of T1DM was 66% in ABC group compared to placebo (p= 0.0048).

Conclusions

TT can effectively prevent T1DM in NOD mice. All in all, this is a proof-of-concept of our method.

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IP-IP PADOVA SIMULATOR: INTRAPERITONEAL INSULIN DELIVERY AND GLUCOSE SENSING

Session Type
Oral Presentations Session
Date
Thu, 28.04.2022
Session Time
16:40 - 18:10
Room
Hall 118
Lecture Time
17:28 - 17:36

Abstract

Background and Aims

Intraperitoneal (IP) route for insulin delivery represents a more physiologic route for type 1 diabetes (T1D) treatment as compared to the subcutaneous (SC) infusion. To develop new IP implantable systems for closed-loop treatment, new insulin kinetics models are mandatory to design robust IP controllers. In order to provide a reliable simulation environment for testing new IP controllers, both IP delivering and sensing (IP-IP) models have to be considered. A new IP-IP simulator is needed.


To this aim, an IP extended version of the FDA accepted SC simulator (IP-T1DS) has been developed.

Methods

A new IP insulin kinetics model has been implemented with IP delivery entering the liver compartment in addition to a new IP glucose sensing model. As an example, a simulated system response of 1-day closed-loop IP and intravenous (IV) insulin delivery in an average patient is depicted in Figure 1.

Results

The new IP-T1DS has generated 100 in silico individuals with T1D incorporating intra- and inter-day variability of insulin sensitivity.

Conclusions

The availability of an IP-T1DS has allowed us to design and test a new control algorithm for IP insulin
delivery and glucose sensing closed-loop therapy.

The work was supported by H2020-FETPROACT Project FORGETDIABETS, n. 951933.

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Figure 1: Simulated scenario. Plasma insulin concentration after an IP and IV insulin infusion in a 1-day three meal scenario: 70 g-carbohydrate (CHO) at dinner ~19:00, 40 g-CHO at breakfast ~8:00 and 70 g-CHO at lunch ~13:00.

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THE ASSOCIATION BETWEEN TIME IN RANGE %, MEASURED BY CONTINUOUS GLUCOSE MONITORING (GCM) AND PHYSICAL & FUNCTIONAL INDICES AMONGST OLDER PEOPLE WITH TYPE 2 DIABETES

Session Type
Oral Presentations Session
Date
Thu, 28.04.2022
Session Time
16:40 - 18:10
Room
Hall 118
Lecture Time
17:36 - 17:44

Abstract

Background and Aims

People with diabetes have an increased risk for mobility disability and a more rapid decline in muscle mass (sarcopenia) compared to those without diabetes. Studies have demonstrated an association between A1C and Sarcopenia. Less is known regarding the relationship with Time In Range (TIR). Aims:To assess among older people with type 2 diabetes, the cross sectional association between: TIR and aerobic capacity, gait speed, strength, balance and frailty indices.

Methods

A cross sectional study, conducted amongst people with diabetes over the age of 60. Participants were provided with a blinded CGM system- (iPro™ professional CGM, Medtronic) for 1 week and underwent elaborate physical-functional assessment in the beginning and at the end of that week.

Results

This analysis pertains to 144 men and women. After adjustment for age and gender, a 1% higher TIR (70-180) was associated with a 0.169 higher score on the 6-minute walk score, a measure of aerobic capacity and endurance (P-value=0.023), 0.119 higher score on the Grip test, a measure of muscle force on the upper limb (P-value=0.039), 0.164 lower score on the 360-turn test, a measure of dynamic balance (P-value= 0.039) and 0.165 lower score on the Timed Up & Go(TUG), a measure of fall risk and balance (P-value=0.037).

Conclusions

Higher % TIR is associated with better scores on indices of muscle force, aerobic capacity and a measure of balance and predicting falls. Future studies are needed in order to elucidated if glucose levels are merely a marker of disease severity, or if there is possibly a causal relationship.

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COMPARING THE BENEFITS OF A PAINLESS LANCING DEVICE IN PEOPLE WITH DIABETES IN IMPROVING SELF-MONITORING FREQUENCY AND HBA1C

Session Type
Oral Presentations Session
Date
Thu, 28.04.2022
Session Time
16:40 - 18:10
Room
Hall 118
Lecture Time
17:44 - 17:52

Abstract

Background and Aims

Pricking of fingertips has always been an impediment in periodic blood glucose monitoring. We compared the benefits of Genteel, a vacuum-based lancing device, in PWD in improving the self-monitoring frequency and HbA1c.

Methods

An open-label, 24-week cross over trial where PWD were matched using propensity score and randomly allocated to GC or CG arm (G- Genteel; C- Conventional). GC exclusively used Genteel for 12 weeks, and then switched to the conventional method of SMBG for additional 12 weeks, and vice versa for CG. A total of 110 patients, including 58 T1D and 52 T2D, were recruited. Both arms were provided with the same glucometer. CG arm used the lancet and lancing device which they were using prior to randomization and GC used Butterfly lancets during the first 3 months. Reduction in HbA1c, %SMBG adherence over 24-weeks and subjective assessment of pain were assessed.

Results

Data from 110 patients (58 T1D and 52 T2D) showed a significant reduction in HbA1c (p<0.05), improved SMBG adherence in T2D (P<0.05) and reported reduction in pain (P<0.05) after using Genteel. A significant number of patients (p<0.05) also reported that they will continue to use Genteel lancing device in the future [Table1].

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Conclusions

This advanced lancing device has helped manage the limitations of conventional lancing devices. T2D showed significant increase in SMBG adherence and HbA1c reduction using genteel than conventional device compared to T1D. Percentage reduction of pain and probability of using genteel in both T1D and T2D was approximately same while probability of using conventional device was comparatively less.

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PERIOPERATIVE CLOSED-LOOP INSULIN DELIVERY VERSUS STANDARD INSULIN THERAPY - A RANDOMISED CONTROLLED PARALLEL CLINICAL TRIAL IN ADULTS WITH TYPE 2 DIABETES

Session Type
Oral Presentations Session
Date
Thu, 28.04.2022
Session Time
16:40 - 18:10
Room
Hall 118
Lecture Time
17:52 - 18:00

Abstract

Background and Aims

Given the increasing prevalence and clinical relevance of perioperative hyperglycaemia, there is an ongoing interest in development of novel approaches to optimize glycaemic control in the surgical population. We evaluated the efficacy and safety of fully automated closed-loop (CL) compared with standard insulin therapy in adults with type 2 diabetes (T2D) undergoing elective surgery.

Methods

In an open-label, single-centre, randomised, parallel study, 45 adults with T2D (15 females, mean±SD: age 68±12years, HbA1c 7.5±1.8%) undergoing elective surgery (55.6% abdominal, 22.2% cardiovascular, 2.2% thoracic, 6.7% neurosurgerical, 11.1% orthopaedic) were randomized to either receive fully CL glucose control (CamAPS HX) using Fiasp or standard insulin therapy (control). The primary outcome was the %time from hospital admission to discharge with glucose levels within the target range (5.6 to 10.0mmol/L), as measured by continuous glucose monitoring. Trial registration NCT04361799.

Results

Twenty-three were assigned to CL, and 22 to the control group. The %time in target glucose range (5.6 to 10.0mmol/L) was 74.8±10.3% with CL vs. 53.9±20.6% with control; mean difference 20.9% [95%CI 10.9 to 30.9%]; P<0.001). Mean glucose was lower with CL than control (8.0±0.7 vs. 9.4±2.5mmol/L; P=0.026). Time in hypoglycaemia did not differ between groups (<3.0mmol/L; median[IQR] 0.0 [0.0;0.02%] vs. 0.0[0.0;0.2%]; P=0.92. No between-group difference was observed for total daily insulin requirements (P=0.72) and length of surgery (P=0.52). No study-related serious adverse events occurred in either group.

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Conclusions

Fully CL improved glucose control without increasing the risk of hypoglycaemia compared to standard insulin therapy in adults with T2D undergoing elective surgery.

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GLYCEMIC CARE OPTIMIZATION IN THE HOSPITAL USING CLINICAL DECISION SUPPORT HELPS REDUCE LENGTH OF STAY

Session Type
Oral Presentations Session
Date
Thu, 28.04.2022
Session Time
16:40 - 18:10
Room
Hall 118
Lecture Time
18:00 - 18:08

Abstract

Background and Aims

Dysglycemia impacts resources utilization and outcomes in hospitalized patients. Clinical Decision Support (CDS) assists in overcoming barriers to care. We aimed to study the impact of an alert-based CDS tool addressing insulin use and glucose control on hospital length of stay (LOS).

Methods

A Clinical Decision Support tool was embedded in the electronic medical record. It captured gaps in glycemic care using data driven algorithms and provided real-time glucose management and insulin utilization guidelines to providers. The tool was available intermittently in records of hospitalized adults over a 12-months period. LOS during active and inactive periods of the tool, each lasting 6 months, was compared invoking a linear model for repeated measures.

Results

Among a total of 4,788 admissions, average LOS was shortened in patients with dysglycemia while the tool was active compared to conventional care. LOS was reduced in patients with gaps in glycemic care in the following manner: in all admissions -5.7 hours (p=0.057); patients with diabetes and hyperglycemia, -6.4 hours (p=0.054); stress hyperglycemia, -31.0 hours (p=0. 054); recurrent hypoglycemia, -29.1 hours (p=0.074); and patients admitted to medical services, -8.4 hours (p=0.039).

Conclusions

A Clinical Decision Support tool embedded in the electronic medical record addressing dysglycemia in the hospital contributes to reducing LOS, which represents a clinical and an economic outcome. Our study highlights the importance of developing comprehensive programs and testing outcomes associated to Clinical Decision Support beyond process improvement and intermediary outcomes. Our findings are relevant to the domains of quality, safety, efficiency, and equity in hospital care.

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