OBJECTIVE: The safety and efficacy of insulin analogue insulin aspart (IAsp) have been demonstrated in a randomised clinical trial in pregnant women with Type 1 diabetes (T1D), and IAsp is widely used during pregnancy. The aim of this study was to assess glycaemic control and safety of IAsp versus other bolus insulins in Type 1 diabetic pregnancy in a real-world setting.
METHODS: This was a post hoc analysis of a prospective cohort study of 1840 pregnant women with T1D, treated with IAsp (n = 1434) or other bolus insulins (n = 406) in the Diabetes Pregnancy Registry. The primary (composite) outcome was the proportion of pregnancies resulting in major congenital malformations or perinatal or neonatal death. Secondary outcomes included all HbA1c values measured immediately before and during pregnancy and major hypoglycaemia, as well as abortion, pre-eclampsia, pre-term delivery, large for gestational age at birth, stillbirth and fetal malformations.
RESULTS: There were no significant differences found in any of the pregnancy outcomes between treatment with IAsp and other bolus insulins in either the crude or propensity score-adjusted analyses. However, maternal HbA1c was lower in the IAsp group at the end of the third trimester (adjusted difference, -0.16% point [95% CI -0.28;-0.05]; -1.8 mmol/mol [95% CI -3.1;-0.6]; p = 0.0046).
CONCLUSIONS: No significant differences in safety or pregnancy outcomes were demonstrated when comparing treatment with IAsp versus other bolus insulins in women with T1D during pregnancy. The observed improvement in HbA1c with IAsp in late pregnancy should be confirmed in other studies.

UNASSIGNED: We evaluated a potential move from one rapid-acting insulin analog to another, or their biosimilars, to aid better and faster decisions for diabetes management.
UNASSIGNED: A systematic literature review was performed according to PRISMA reporting guidelines. The MEDLINE/EMBASE/COCHRANE databases were searched for randomized control trials (RCTs) comparing aspart/lispro in type-1 (T1D) and type-2 (T2D) diabetes. The methodological quality of the included studies was assessed using the Cochrane Collaboration\'s risk of bias assessment criteria.
UNASSIGNED: Of the 753 records retrieved, the six selected efficacy/safety RCTs and the additional three hand-searched pharmacokinetics/pharmacodynamics RCTs showed some heterogeneity in the presentation of the continuous variables; however, collectively, the outcomes demonstrated that lispro and aspart had comparable efficacy and safety in adult patients with T1D and T2D. Both treatments yielded a similar decrease in glycated hemoglobin (HbA1c) and had similar dosing and weight changes, with similar treatment-emergent adverse events (TEAE) and serious adverse event (SAE) reporting, similar hypoglycemic episodes in both T1D and T2D populations, and no clinically significant differences for hyperglycemia, occlusions or other infusion site/set complications.
UNASSIGNED: Aspart and lispro demonstrate comparative safety and efficacy in patients with T1D/T2D. Since both are deemed equally suitable for controlling prandial glycemic excursions and both have similar safety attributes, they may be used interchangeably in clinical practice.
UNASSIGNED: CRD42023376793.

BACKGROUND: In type 1 diabetes, carbohydrate counting is the standard of care to determine prandial insulin needs, but it can negatively affect quality of life. We developed a novel insulin-and-pramlintide closed-loop system that replaces carbohydrate counting with simple meal announcements.
METHODS: We performed a randomised crossover trial assessing 14 days of (1) insulin-and-pramlintide closed-loop system with simple meal announcements, (2) insulin-and-placebo closed-loop system with carbohydrate counting, and (3) insulin-and-placebo closed-loop system with simple meal announcements. Participants were recruited at McGill University Health Centre (Montreal, QC, Canada). Eligible participants were adults (aged ≥18 years) and adolescents (aged 12-17 years) with type 1 diabetes for at least 1 year. Participants were randomly assigned in a 1:1:1:1:1:1 ratio to a sequence of the three interventions, with faster insulin aspart used in all interventions. Each intervention was separated by a 14-45-day wash-out period, during which participants reverted to their usual insulin. During simple meal announcement interventions, participants triggered a prandial bolus at mealtimes based on a programmed fixed meal size, whereas during carbohydrate counting interventions, participants manually entered the carbohydrate content of the meal and an algorithm calculated the prandial bolus based on insulin-to-carbohydrate ratio. Two primary comparisons were predefined: the percentage of time in range (glucose 3·9-10·0 mmol/L) with a non-inferiority margin of 6·25% (non-inferiority comparison); and the mean Emotional Burden subscale score of the Diabetes Distress Scale (superiority comparison), comparing the insulin-and-placebo system with carbohydrate counting minus the insulin-and-pramlintide system with simple meal announcements. Analyses were performed on a modified intention-to-treat basis, excluding participants who did not complete all interventions. Serious adverse events were assessed in all participants. This trial is registered on ClinicalTrials.gov, NCT04163874.
RESULTS: 32 participants were enrolled between Feb 14, 2020, and Oct 5, 2021; two participants withdrew before study completion. 30 participants were analysed, including 15 adults (nine female, mean age 39·4 years [SD 13·8]) and 15 adolescents (eight female, mean age 15·7 years [1·3]). Non-inferiority of the insulin-and-pramlintide system with simple meal announcements relative to the insulin-and-placebo system with carbohydrate counting was reached (difference -5% [95% CI -9·0 to -0·7], non-inferiority p<0·0001). No statistically significant difference was found in the mean Emotional Burden score between the insulin-and-pramlintide system with simple meal announcements and the insulin-and-placebo system with carbohydrate counting (difference 0·01 [SD 0·82], p=0·93). With the insulin-and-pramlintide system with simple meal announcements, 14 (47%) participants reported mild gastrointestinal symptoms and two (7%) reported moderate symptoms, compared with two (7%) participants reporting mild gastrointestinal symptoms on the insulin-and-placebo system with carbohydrate counting. No serious adverse events occurred.
CONCLUSIONS: The insulin-and-pramlintide system with simple meal announcements alleviated carbohydrate counting without degrading glucose control, although quality of life as measured by the Emotional Burden score was not improved. Longer and larger studies with this novel approach are warranted.
BACKGROUND: Juvenile Diabetes Research Foundation.

An inter-drug approach, applying pharmacokinetic information for insulin analogs in different animal species, rat, dog and pig, performed better compared to allometric scaling for human translation of intra-venous half-life and only required data from a single animal species for reliable predictions. Average fold error (AFE) between 1.2-1.7 were determined for all species and for multispecies allometric scaling AFE was 1.9. A slightly larger prediction error for human half-life was determined from in vitro human insulin receptor affinity data (AFE on 2.3-2.6). The requirements for the inter-drug approach were shown to be a span of at least 2 orders of magnitude in half-life for the included drugs and a shared clearance mechanism. The insulin analogs in this study were the five fatty acid protracted analogs: Insulin degludec, insulin icodec, insulin 320, insulin 338 and insulin 362, as well as the non-acylated analog insulin aspart.

UNASSIGNED: We systematically reviewed and analyzed the efficacy and safety of insulin degludec/insulin as-part (IDegAsp) versus biphasic insulin aspart 30 (BIAsp 30) in patients with type 2 diabetes (T2D).
UNASSIGNED: We used computers to search the Embase, PubMed, Clinical Trials, and the Cochrane Library database, and collected randomized controlled trials (RCTs) on the treatment of IDegAsp versus BIAsp 30 in T2D patients. The research period was from the establishment of the database to May 19, 2023. We used Review Manager 5.20 statistical software for systematic meta-analysis.
UNASSIGNED: We included 8 RCTs with 2281 participants. IDegAsp was better to BIAsp30 in improving fasting plasma glucose (FPG) levels (P<0.001) and reducing the endpoint daily average insulin dose (P<0.01). Furthermore, compared with BIAsp30, IDegAsp significantly reduced the risk of nocturnal hypoglycemic events (P<0.001). However, there was no significant difference in the improvement of body weight change (P=0.99), glycosylated hemoglobin (P=0.50), the overall risk of hypoglycemic events (P=0.57) and adverse events (P=0.89) between the two groups.
UNASSIGNED: Compared with BIAsp30, IDegAsp could significantly reduce FPG levels, insulin dosage, and the risk of nocturnal hypoglycemic events in T2D patients, without increasing the overall risk of adverse events.

UNASSIGNED: Psychological insulin resistance (PIR), which refers to the reluctance of diabetic patients to use insulin, is a frequently encountered clinical issue. Needle-free injection (NFI) offers advantages in terms of expediting insulin absorption and mitigating adverse reactions related to injection. To evaluate the effects of subcutaneous injection of insulin aspart 30 with NFI on PIR and insulin dosage in patients with type 2 diabetes mellitus (T2DM).
UNASSIGNED: Sixty-four patients with T2DM participated in this randomized, prospective, open, crossover study. Insulin aspart 30 was administered subcutaneously to each subject via QS-P NFI and Novo Pen 5 (NP) successively. The effects of NFI on PIR were analyzed. Differences in insulin dosage, glycemic variability, and injection safety were compared at similar levels of glycemic control.
UNASSIGNED: After the administration of NFI, the insulin treatment attitude scale score decreased (53.7 ± 7.3 vs. 58.9 ± 10.7, p<0.001), the insulin treatment adherence questionnaire score increased (46.3 ± 4.9 vs. 43.8 ± 7.1, p<0.001), and the insulin treatment satisfaction questionnaire score increased (66.6 ± 10.5 vs. 62.4 ± 16.5, p<0.001). At the same blood glucose level, NFI required a smaller dosage of insulin aspart 30 compared with that of NP (30.42 ± 8.70 vs. 33.66 ± 9.13 U/d, p<0.001). There were no differences in glycemic variability indices (standard deviation, mean amplitude of glycemic excursion or coefficient of variation) between the two injection methods. Compared with NP, NFI did not increase the incidence of hypoglycemia (17.2% vs. 14.1%, p=0.774), and it decreased the incidence of induration (4.7% vs. 23.4%, p=0.002) and leakage (6.3% vs. 20.3%, p=0.022) while decreasing the pain visual analog scale score (2.30 ± 1.58 vs. 3.11 ± 1.40, p<0.001).
UNASSIGNED: NFI can improve PIR in patients with T2DM and be used with a smaller dose of insulin aspart 30 while maintaining the same hypoglycemic effect.
UNASSIGNED: https://www.chictr.org.cn/, identifier ChiCTR2400083658.

BACKGROUND: People with diabetes require insulin to regulate blood glucose (BG); rapid-acting insulin analogs (RAIA) represent one approach for BG management. New fast-acting RAIA administered at the start of a meal suppress postprandial BG better than conventional RAIA. New RAIA are expected to confer higher treatment satisfaction and improved quality of life (QOL) than conventional RAIA.
METHODS: This cross-sectional, web-based survey in Japan (November 2022) included people with diabetes (type 1/2), aged ≥ 18 years, registered in the Rakuten Insight Diabetes Panel, using new and/or conventional RAIA. RAIA-specific satisfaction was evaluated by questions on RAIA use (scores: 1 [not at all satisfied]; 7 [very satisfied]) and QOL by the Diabetes Therapy-Related (DTR)-QOL questionnaire (scores: 0-100, 100 = best) for the whole population (primary endpoint) and for new versus conventional RAIA users (secondary endpoint). Multiple regression models were used to compare new versus conventional RAIA users.
RESULTS: The analysis population comprised 217 people with diabetes (new RAIA, n = 109; conventional RAIA, n = 108). Mean (standard deviation) RAIA-specific satisfaction scores ranged from 5.1 (1.2) to 5.4 (1.2); DTR-QOL total score was 51.6 (20.4). RAIA satisfaction scores were numerically higher for new versus conventional RAIA users; no difference in DTR-QOL total score was observed. DTR-QOL satisfaction with treatment domain score was significantly higher in new versus conventional RAIA users (least squares mean difference [standard error]: 7.3 [3.1]; 95% confidence interval: 1.2, 13.4; P = 0.0197). RAIA-specific satisfaction was higher among patients who discussed BG sufficiently with their doctor versus those who did not.
CONCLUSIONS: New RAIA users have greater treatment satisfaction than conventional RAIA users. QOL was similar among new and conventional RAIA users, except for satisfaction with treatment, which was significantly higher among new RAIA users. Detailed explanations from the doctor to the person with diabetes about the relationship between new RAIA and BG status are essential. A graphical plain language summary is available with this article.

OBJECTIVE: To investigate the impact of combining metformin with insulin aspart on blood glucose control, renal injury, and pregnancy outcome in gestational diabetes mellitus (GDM) patients.
METHODS: In this retrospective analysis, the clinical data of 140 GDM patients treated at Baoji Maternal and Child Health Hospital between March 2020 and March 2022 were studied. The patients were divided into a control group (insulin aspart alone, n=64) and an observation group (combination of insulin aspart and metformin, n=76) according to their treatment regimen. The blood glucose metabolism, renal injury markers, and pregnancy outcomes between the two groups were assessed and compared.
RESULTS: The observation group demonstrated significantly lower levels of blood glucose metabolism markers (fasting plasma glucose [FPG], fasting insulin [FINS], mean amplitude of glycemic excursions [MAGE], and mean of daily differences [MODD]), renal injury indicators (microalbuminuria [mAlb], serum cystatin C [CysC], free fatty acids [FFA], and neutrophil gelatinase-associated lipocalin [NGAL]), and inflammatory markers (interleukin-6 [IL-6], transforming growth factor-β1 [TGF-β1], and lipoprotein-associated phospholipase A2 [Lp-PLA2]) compared to the control group (all P<0.05). Additionally, the incidence of adverse pregnancy outcomes in both newborns and mothers was lower in the observation group (P<0.05). Logistic regression analysis identified the treatment regimen, patient age, and pre-pregnancy BMI as independent risk factors for adverse pregnancy outcome.
CONCLUSIONS: The combination of metformin and insulin aspart in treating GDM can effectively reduce blood glucose levels, mitigate renal injury, and improve pregnancy outcome. This treatment approach presents a viable option for optimizing maternal and fetal health in GDM cases.

UNASSIGNED: Intensive insulin regimens are recommended to achieve glycemic goals in children and adolescents with type 1 diabetes. Fast-acting insulin aspart (faster aspart) is a new formulation of insulin aspart (IAsp) in which L-arginine and niacinamide are added to assure formulation stability, early absorption, and ultra-fast action. This meta-analysis compares faster aspart with IAsp for blood sugar control in children with type 1 diabetes. This study suggested treating diabetes with insulin, especially in children with type 1 diabetes.
UNASSIGNED: PubMed, MEDLINE, Embase, Cochrane Library, Web of Science, and Google Scholar were searched from 2000 to 2023 without language restrictions. Blood glucose monitoring, HbA1c, care model, insulin aspart, IAsp, faster aspart, type 1 diabetes, and pediatrics are Mesh keywords. Cochrane Q statistics and index tested heterogeneity. To account for heterogeneity, Q=145.99 (P-value < 0.001) and =97.26%, and the random-effect model was used to aggregate primary study results. The meta-analysis of randomized-controlled trials was conducted in accordance with PRISMA standards.
UNASSIGNED: The overall estimate measure i.e. mean difference was found to be 5.44 [0.45, 10.44] and 7.71 [7.16, 8.26] which indicate significant reduction in the HbA1C level in the fast acting insulin aspart group as compared to the IAsp in T1D. However, the mean difference with respect to BMI was found to be -0.06 [-0.60, 0.48] which indicate non-significant reduction.
UNASSIGNED: Faster aspart had faster onset and more early exposure than IAsp in children and adolescents with greater and more variable anti-insulin antibody levels than adults did. Hence fast-acting insulin aspart may provide better glucose control than IAsp in T1D.

OBJECTIVE: IDegAsp (Ryzodeg 70/30), a unique premixed formulation of long-acting insulin degludec and rapid-acting insulin aspart, is increasing in use. Management of IDegAsp during hospitalisation is challenging because of degludec\'s ultra-long duration of action. We investigated inpatient glycaemia in patients treated with IDegAsp compared to biphasic insulin aspart (BIAsp30; Novomix30).
METHODS: We performed a retrospective observational study at two hospitals assessing inpatients with type 2 diabetes treated with IDegAsp or BIAsp30 prior to and during hospital admission. Standard inpatient glycaemic outcomes were analysed based on capillary blood glucose (BG) measurements.
RESULTS: We assessed 88 individuals treated with IDegAsp and 88 HbA1c-matched individuals treated with BIAsp30. Patient characteristics, including insulin dose at admission, were well matched, but the IDegAsp group had less frequent twice-daily insulin dosing than the BIAsp30 group (49% vs 87%, P < 0.001). Patient-days with BG <4 mmol/L were not different (10.6% vs 9.9%, P = 0.7); however, the IDegAsp group had a higher patient-day mean BG (10.4 (SD 3.4) vs 10.0 (3.4) mmol/L, P < 0.001), and more patient-days with mean BG >10 mmol/L (48% vs 38%, P < 0.001) compared to the BIAsp30 group. Glucose was higher in the IDegAsp group in the evening (4 PM to midnight) (11.6 (SD 4.0) vs 10.9 (4.6) mmol/L, P = 0.004), but not different at other times during the day.
CONCLUSIONS: Inpatients treated with IDegAsp compared to BIAsp30 had similar hypoglycaemia incidence, but higher hyperglycaemia incidence, potentially related to less frequent twice-daily dosing. With the increasing use of IDegAsp in the community, development of hospital management guidelines for this insulin formulation is needed.