Background and Aims

Insulin glargine 300U/ml (Gla-300) is a second-generation basal insulin analogue that is associated with lower risk of hypoglycaemia and glycaemic variability (GV). We compared GV and time-in-range (TIR) in Chinese T2D patients initiated on once daily bedtime Gla-300 versus NPH.

Methods

This was a 24-week, 1:1 randomized, open-label study, comparing patient-adjusted titration of Gla-300 versus NPH at bedtime in 50 insulin-naïve T2D patients on maximal oral antidiabetic drugs. The starting dose was 0.2U/kg/day and with self-titration of 1 unit per week to achieve a target fasting glucose of 4.4 to 6 mmol/l, without hypoglycaemia. Patients had seven-day professional continuous glucose monitoring (CGM) (Medtronic iPro®2 with Enlite sensor) at baseline, week 12 and 24. The nocturnal period was defined as 00:00 to 06:00 hours.

Results

Percentage TIR between 3.9 to 10mmol/l was similar in NPH and Gla-300 groups at baseline (Mean ±SD 48±16 versus 47±22 %). At 24 weeks, overall TIR was similar between NPH and Gla-300 groups (61±16 versus 60±17%) with no difference in GV. During the nocturnal period, % time below 3.9mmol/l was significantly lower in the Gla-300 group (p =0.04, Fig 1). Nocturnal GV as expressed by the coefficient of variation was significantly lower in Gla-300 verus NPH groups (25±6% versus 34±9% , p = 0.008). There were no differences between groups in TIR or GV during daytime hours.

Conclusions

Once daily bedtime Gla-300 was associated with lower nocturnal GV and CGM-detected hypoglycaemia as compared with NPH insulin.

Funding: Sanofi investigator-initiated study

Background and Aims

The Step‑by‑Step trial (NCT02906917) compared the efficacy of insulin degludec/insulin aspart (IDegAsp) OD/BID with insulin glargine 100 units/mL (IGlar U100) OD plus insulin aspart (IAsp) OD/BID/TID over a 38-week treatment period, in patients with type 2 diabetes (T2D) (Figure 1). This post hoc analysis used patient-level modelling to assess predicted risk of hypoglycaemia with IDegAsp OD/BID versus IGlar U100 OD plus IAsp OD/BID/TID across a range of glycaemic values.

Methods

For each patient at each visit where HbA_1c was recorded, normalised HbA_1c values were linked with predicted risk of severe (ADA classification) or BG‑confirmed (<3.1 mmol/L) symptomatic hypoglycaemia since last visit. From this modelled association, estimated differences in glycaemic control with IDegAsp versus IGlar U100 plus IAsp at Weeks 26 and 38 were calculated using hypoglycaemia rate ratios from the trial.

Results

For the same HbA_1c reduction (e.g. 7.0% to 6.0%), the increase in predicted hypoglycaemia rate with IDegAsp was smaller (0.75 to 0.90; 20% increase) versus IGlar U100 plus IAsp (1.46 to 2.12; 45% increase; Figure 2). Estimated differences in glycaemic control with IDegAsp versus IGlar U100 plus IAsp at the same hypoglycaemia rates at Weeks 26 and 38 were −0.21% and −0.30%, respectively.

Conclusions

This analysis demonstrates a reduced risk of hypoglycaemia with IDegAsp versus IGlar U100 plus IAsp across a range of glycaemic values, in patients with T2D. The modelled association shows that at the same hypoglycaemia rate, IDegAsp is expected to result in a greater reduction in HbA_1c versus IGlar U100 plus IAsp.

Background and Aims

URLi is a novel prandial insulin lispro formulation developed to more closely match physiological insulin secretion. URLi was efficacious with a similar safety profile to lispro in phase 3 studies. Ambulatory glucose profiles were evaluated in 269 (22%) patients (pts) in PRONTO-T1D assigned to double-blind URLi (n=97) or lispro (n=99) given at the start of the meal, or open-label URLi (n=73) given 20 min after the meal (URLi +20). Primary endpoint was incremental AUC_0-2h (iAUC) after breakfast.

Methods

Blinded CGM (Dexcom G4 Platinum) was worn for 14 days before baseline and week 26.

Results

Pts reflected main study population: mean A1C at week 26 was 7.15% - URLi, 7.12% - lispro, 7.35% - URLi+20. Compared to lispro, URLi had significantly smaller breakfast iAUC_0-2h with estimated treatment difference (ETD) -28.1 mg.h/dL, p=0.048; more daytime TIR (71-180 mg/dL) ETD +43.6 min, p=0.020; and similar nighttime TIR. Time <50 mg/dL and >180 mg/dL were both numerically lower with URLi in daytime, with less time <50 mg/dL at nighttime vs. lispro: 7.0 vs. 12.6 min, p=0.023. PPG control in pts who marked meal times improved with URLi compared to lispro and URLi +20 (Figure).

Conclusions

When injected at the start of the meal, URLi resulted in significantly better PPG control and increased daytime TIR vs. lispro without increasing time in hypoglycemia. CGM results augment findings from PRONTO-T1D.

Background and Aims

Currently, Insulin is an obligatory medication in T1DM. However, protection and preservation of residual β-cell function are of the highest priority because even miserable amounts of endogenous insulin are critical for maintaining proper diabetes control and complications avoidance.

DPP-4i family can help to reverse β cell damage. Proton Pump Inhibitors (PPIs) administration correlate with improved β cell function. GABA (Gamma Amino Butyric Acid) induces the suppression of glucagon, while stimulates β cells regeneration.

Methods

We report a two-year retrospective analysis of 56 Type 1 Diabetes (T1DM) patients treated with a combination of DPP4i, PPi, GABA. 19 of them fulfilled the protocol criteria. Parameters “Before-and-After” were compared. We also developed the “T1DM probability score”. Patients with more than five points were considered to suffer from T1DM. A/GAD antibodies were checked in 14 (74%) patients, of them - found positive in 10 (71.4%).

Results

HbA1c decreased from 8.6±2.1 to 6.5±1.1 % (p-0,001). Insulin demands reduced from 26.0±23.4 to 10.8±14.4 units per day (p-0,003). BMI was stable: 23.4±2.5 kg/m2 before vs. 23.0±2.5 kg/m2 after (p-0,28). CGM showed Hypoglycemia TIR : 1.9±2.6 % vs.6.3±11.4 % (p-0,50). Normoglycemia TIR: 56,5± 32,8 vs. 62,1± 29,2% (p-0,064). Hyperglycemia TIR 41.6±33.1 vs. 31.6 ± 30.5% (p-0,02). Six patients (31.6%) stopped their insulin Injections for at least 26 weeks’period. Only one patient returned to insulin injections after 26 weeks .

Conclusions

This study demonstrates the efficacy of proposed therapy in T1DM. 31.6% of participants entered a long-term remission and became Insulin – free. All-in-all, this study is a proof of our concept.

Background and Aims

The preservation of the reserve of beta cells in new-onset T1DM by immunomodulation in addition to the incretin effect seems to be possible with an association of DPP-4i and vitamin D3. DPP-4i due to their anti-inflammatory and immunomodulating effects and increase GLP-1, have protective effects on beta cells.Vitamin D also has beneficial actions in insulin synthesis, secretion, and sensitivity.The aim this work is reporting the effects of the association sitagliptin plus vitamin D3 to prolong the ¨honeymoon phase¨ in new-onset T1D.

Methods

12 patients with new-onset T1D, 7 women, median age 15 y (6-39), median diabetes 12 months (6-100), undergoing treatment with sitagtliptin 100 mg plus vitamin D3 5,000 IU were evaluated their time in remission, C-peptide levels, evolution of HbA1c and insulin dose. We used IDAA1C (insulin dose-adjusted A1C) as the remission criterion. IDAA1C = A1C (percent) + [4 x insulin dose (UI/kg/24 h)]. A IDAA1C <= 9 indicates remission. All patients or their parents signed a consent form and the data analysis was approved by the UNIVAG Ethics Committee.

Results

BMI was 18,7 kg/m2 (+/- 3,2), 6 patients had KAD, median honeymoon time was 10 months (6-87), final mean insulin dose was 0,15 IU/kg/24 h (+/-0,24), 5 patients are without insulin (6-87 months), mean IDAA1C was 6,75 (+/-1,1), initial HbA1c was 11,69% (+/-2) and final HbAc1c was 5,59% (+/-1,88). Fasting initial C-peptide was 0,86 ng/dl (+/-0,47) and final C peptide was 0,89 ng/dl (+/-0,57)

Conclusions

Honeymoon phase prolongation in T1DM is possible with sitagliptin plus vitamin D3, even without insulin for 87 months.

Background and Aims

Nasal glucagon (NG), a ready-to-use drug-device combination for treatment of severe hypoglycemia (SH), contains 3 mg glucagon dry powder that is absorbed through the nasal mucosa. We aimed to examine the efficacy and safety of NG in reversing clinically significant insulin-induced hypoglycemia in adults with diabetes.

Methods

Post-hoc analyses were performed to assess the efficacy and safety of NG compared to injectable glucagon (IG) using data from participants in 3 randomized studies whose nadir blood glucose (BG) was <3.0 mmol/L (54 mg/dL). The analysis included 169 adults (NG=156, IG=133). Treatment success was defined as an increase in BG to ≥3.9 mmol/L (70 mg/dL) or an increase of ≥1.1 mmol/L (20 mg/dL) from nadir BG within 30 min of receiving glucagon. Tolerability was assessed through reported treatment-emergent adverse events (TEAEs) and solicited using a Nasal and Non-Nasal Score Questionnaire.

Results

NG (99.4%) and IG (100%) successfully reversed clinically significant hypoglycemia, and the mean time to treatment success (preparation time excluded) was 14 min and 12 min, respectively (p<0.001). BG changes were similar between treatments (Figure). No serious AEs occurred. TEAEs with an incidence ≥10% for NG were nausea, vomiting, and headache. Worsening of nasal and non-nasal symptoms experienced by ≥10% of patients up to 60 min after NG included runny nose, nasal congestion, nasal itching, watery eyes, redness of eyes, and itchy eyes.

Conclusions

NG was efficacious and well tolerated in reversing clinically significant hypoglycemia in adults with diabetes, supporting NG as a rescue treatment for SH.

Background and Aims

Higher bolus frequency is expected to correlate with better glycemic control; however, there is little real-world data quantifying this trend. This study retrospectively assessed glycemic outcomes stratified by bolus frequency for a large cohort of adults with T1D using the Omnipod® Insulin Management System (Insulet Corp., Acton, MA) with an integrated BG meter (Abbott Diabetes Care Inc., Alameda, CA) and data management system (Glooko, Mountain View, CA).

Methods

Insulin pump data uploaded to the data management system from February-August 2019 were matched via device serial number to a second database of self-reported demographic data and de-identified. Data from ≥3 mo of system use per user were analyzed. Glucose Management Indicator (GMI) and percentage of readings <54 and 70-180mg/dL were calculated based on ≥14 days of BG meter readings for users grouped by average bolus frequency (<3, 3-4.99, 5-7.99, or ≥8/day).

Results

In 4,483 adults aged ≥18y with T1D (aged 41±16y, 64% female), average bolus frequency was 5.2±2.5/day, with 37% of users bolusing 3-4.99 times/day. Increased bolus frequency was correlated with improved GMI (Figure), decreased percentage of readings <54mg/dL, and increased percentage of readings 70-180mg/dL. The percentage of readings 70-180mg/dL increased from 39% with infrequent bolusing (<3/day) to 55% with frequent bolusing (≥8/day), while the percentage of readings <54mg/dL decreased from 2.8% to 1.7%.

Conclusions

Higher bolus frequency was associated with better glycemic control as measured by GMI and percentage of readings in target range in a large cohort of adults with T1D using the Omnipod System in this real-world observational study.