The Importance of Intra-Islet Communication in the Function and Plasticity of the Islets of Langerhans during Health and Diabetes.

Islets of Langerhans are anatomically dispersed within the pancreas and exhibit regulatory coordination between islets in response to nutritional and inflammatory stimuli. However, within individual islets, there is also multi-faceted coordination of function between individual beta-cells, and between beta-cells and other endocrine and vascular cell types. This is mediated partly through circulatory feedback of the major secreted hormones, insulin and glucagon, but also by autocrine and paracrine actions within the islet by a range of other secreted products, including somatostatin, urocortin 3, serotonin, glucagon-like peptide-1, acetylcholine, and ghrelin. Their availability can be modulated within the islet by pericyte-mediated regulation of microvascular blood flow. Within the islet, both endocrine progenitor cells and the ability of endocrine cells to trans-differentiate between phenotypes can alter endocrine cell mass to adapt to changed metabolic circumstances, regulated by the within-islet trophic environment. Optimal islet function is precariously balanced due to the high metabolic rate required by beta-cells to synthesize and secrete insulin, and they are susceptible to oxidative and endoplasmic reticular stress in the face of high metabolic demand. Resulting changes in paracrine dynamics within the islets can contribute to the emergence of Types 1, 2 and gestational diabetes.

Investigating the Effects of Diet-Induced Prediabetes on Skeletal Muscle Strength in Male Sprague Dawley Rats.

Type 2 diabetes mellitus, a condition preceded by prediabetes, is documented to compromise skeletal muscle health, consequently affecting skeletal muscle structure, strength, and glucose homeostasis. A disturbance in skeletal muscle functional capacity has been demonstrated to induce insulin resistance and hyperglycemia. However, the modifications in skeletal muscle function in the prediabetic state are not well elucidated. Hence, this study investigated the effects of diet-induced prediabetes on skeletal muscle strength in a prediabetic model. Male Sprague Dawley rats were randomly assigned to one of the two groups (n = 6 per group; six prediabetic (PD) and six non-pre-diabetic (NPD)). The PD group (n = 6) was induced with prediabetes for 20 weeks. The diet that was used to induce prediabetes consisted of fats (30% Kcal/g), proteins (15% Kcal/g), and carbohydrates (55% Kcal/g). In addition to the diet, the experimental animals (n = 6) were supplied with drinking water that was supplemented with 15% fructose. The control group (n = 6) was allowed access to normal rat chow, consisting of 35% carbohydrates, 30% protein, 15% fats, and 20% other components, as well as ordinary tap water. At the end of week 20, the experimental animals were diagnosed with prediabetes using the American Diabetes Association (ADA) prediabetes impaired fasting blood glucose criteria (5.6-6.9 mmol/L). Upon prediabetes diagnosis, the animals were subjected to a four-limb grip strength test to assess skeletal muscle strength at week 20. After the grip strength test was conducted, the animals were euthanized for blood and tissue collection to analyze glycated hemoglobin (HbA1c), plasma insulin, and insulin resistance using the homeostatic model of insulin resistance (HOMA-IR) index and malondialdehyde (MDA) concentration. Correlation analysis was performed to examine the associations of skeletal muscle strength with HOMA-IR, plasma glucose, HbA1c, and MDA concentration. The results demonstrated increased HbA1c, FBG, insulin, HOMA-IR, and MDA concentrations in the PD group compared to the NPD group. Grip strength was reduced in the PD group compared to the NPD group. Grip strength was negatively correlated with HbA1c, plasma glucose, HOMA-IR, and MDA concentration in the PD group. These observations suggest that diet-induced prediabetes compromises muscle function, which may contribute to increased levels of sedentary behavior during prediabetes progression, and this may contribute to the development of hyperglycemia in T2DM.

Exploring the Pathophysiology of ATP-Dependent Potassium Channels in Insulin Resistance.

Ionic channels are present in eucaryotic plasma and intracellular membranes. They coordinate and control several functions. Potassium channels belong to the most diverse family of ionic channels that includes ATP-dependent potassium (KATP) channels in the potassium rectifier channel subfamily. These channels were initially described in heart muscle and then in other tissues such as pancreatic, skeletal muscle, brain, and vascular and non-vascular smooth muscle tissues. In pancreatic beta cells, KATP channels are primarily responsible for maintaining the membrane potential and for depolarization-mediated insulin release, and their decreased density and activity may be related to insulin resistance. KATP channels' relationship with insulin resistance is beginning to be explored in extra-pancreatic beta tissues like the skeletal muscle, where KATP channels are involved in insulin-dependent glucose recapture and their activation may lead to insulin resistance. In adipose tissues, KATP channels containing Kir6.2 protein subunits could be related to the increase in free fatty acids and insulin resistance; therefore, pathological processes that promote prolonged adipocyte KATP channel inhibition might lead to obesity due to insulin resistance. In the central nervous system, KATP channel activation can regulate peripheric glycemia and lead to brain insulin resistance, an early peripheral alteration that can lead to the development of pathologies such as obesity and Type 2 Diabetes Mellitus (T2DM). In this review, we aim to discuss the characteristics of KATP channels, their relationship with clinical disorders, and their mechanisms and potential associations with peripheral and central insulin resistance.

The Discovery of New Inhibitors of Insulin-Regulated Aminopeptidase by a High-Throughput Screening of 400,000 Drug-like Compounds.

With the ambition to identify novel chemical starting points that can be further optimized into small drug-like inhibitors of insulin-regulated aminopeptidase (IRAP) and serve as potential future cognitive enhancers in the clinic, we conducted an ultra-high-throughput screening campaign of a chemically diverse compound library of approximately 400,000 drug-like small molecules. Three biochemical and one biophysical assays were developed to enable large-scale screening and hit triaging. The screening funnel, designed to be compatible with high-density microplates, was established with two enzyme inhibition assays employing either fluorescent or absorbance readouts. As IRAP is a zinc-dependent enzyme, the remaining active compounds were further evaluated in the primary assay, albeit with the addition of zinc ions. Rescreening with zinc confirmed the inhibitory activity for most compounds, emphasizing a zinc-independent mechanism of action. Additionally, target engagement was confirmed using a complementary biophysical thermal shift assay where compounds causing positive/negative thermal shifts were considered genuine binders. Triaging based on biochemical activity, target engagement, and drug-likeness resulted in the selection of 50 qualified hits, of which the IC50 of 32 compounds was below 3.5 µM. Despite hydroxamic acid dominance, diverse chemotypes with biochemical activity and target engagement were discovered, including non-hydroxamic acid compounds. The most potent compound (QHL1) was resynthesized with a confirmed inhibitory IC50 of 320 nM. Amongst these compounds, 20 new compound structure classes were identified, providing many new starting points for the development of unique IRAP inhibitors. Detailed characterization and optimization of lead compounds, considering both hydroxamic acids and other diverse structures, are in progress for further exploration.

Association Between Type 1 Diabetes Mellitus and Eating Disorders: A Systematic Review and Meta-Analysis.

BACKGROUND: Previous meta-analyses have shown mixed results regarding the association between eating disorders (EDs) and type 1 diabetes mellitus (T1DM). Our paper aimed to analyse different EDs and disordered eating behaviours that may be practiced by patients with T1DM. METHODS: A literature search of PubMed, Scopus and Web of Science was conducted on 17 January 2023, using the key terms "T1DM," "Eating Disorders" and "Bulimia." Only observational controlled studies were included. The Revman software (version 5.4) was used for the analysis. RESULTS: T1DM was associated with increased risk of ED compared with nondiabetic individuals (RR = 2.47, 95% CI = 1.84-3.32, p-value < 0.00001), especially bulimia nervosa (RR = 2.80, 95% CI = 1.18-6.65, p-value = 0.02) and binge eating (RR = 1.53, 95% CI = 1.18-1.98, p-value = 0.001). Our analysis has shown that increased risk of ED among T1DM persisted regardless of the questionnaire used to diagnose ED; DM-validated questionnaires (RR = 2.80, 95% CI = 1.91-4.12, p-value < 0.00001) and generic questionnaires (RR = 2.03, 95% CI = 1.27-3.23, p-value = 0.003). Prevalence of insulin omission/misuse was 10.3%; diabetic females demonstrated a significantly higher risk of insulin omission and insulin misuse than diabetic males. CONCLUSION: Our study establishes a significant and clear connection between EDs and T1DM, particularly bulimia and binge eating, with T1DM. Moreover, female diabetics are at higher risk of insulin misuse/omission. Early proactive screening is essential and tailored; comprehensive interventions combining diabetes and ED components are recommended for this population, with referral to a specialised psychiatrist.

Non-Invasive Delivery of Insulin for Breaching Hindrances against Diabetes.

Insulin is recognized as a crucial weapon in managing diabetes. Subcutaneous (s.c.) injections are the traditional approach for insulin administration, which usually have many limitations. Numerous alternative (non-invasive) slants through different routes have been explored by the researchers for making needle-free delivery of insulin for attaining its augmented absorption as well as bioavailability. The current review delineating numerous pros and cons of several novel approaches of non-invasive insulin delivery by overcoming many of their hurdles. Primary information on the topic was gathered by searching scholarly articles from PubMed added with extraction of data from auxiliary manuscripts. Many approaches (discussed in the article) are meant for the delivery of a safe, effective, stable, and patient friendly administration of insulin via buccal, oral, inhalational, transdermal, intranasal, ocular, vaginal and rectal routes. Few of them have proven their clinical efficacy for maintaining the glycemic levels, whereas others are under the investigational pipe line. The developed products are comprising of many advanced micro/nano composite technologies and few of them might be entering into the market in near future, thereby garnishing the hopes of millions of diabetics who are under the network of s.c. insulin injections.

Comparing Continuous Glucose Monitoring and Blood Glucose Monitoring in Adults With Inadequately Controlled, Insulin-Treated Type 2 Diabetes (Steno2tech Study): A 12-Month, Single-Center, Randomized Controlled Trial.

OBJECTIVE: To compare the 12-month effects of continuous glucose monitoring (CGM) versus blood glucose monitoring (BGM) in adults with insulin-treated type 2 diabetes. RESEARCH DESIGN AND METHODS: This is a single-center, parallel, open-label, randomized controlled trial including adults with inadequately controlled, insulin-treated type 2 diabetes from the outpatient clinic at Steno Diabetes Center Copenhagen, Denmark. Inclusion criteria were ≥18 years of age, insulin-treated type 2 diabetes, and HbA1c ≥7.5% (58 mmol/mol). Participants were randomly assigned (1:1) to 12 months of either CGM or BGM. All participants received a diabetes self-management education course and were followed by their usual health care providers. Primary outcome was between-group differences in change in time in range (TIR) 3.9-10.0 mmol/L, assessed at baseline, after 6 and 12 months by blinded CGM. The prespecified secondary outcomes were differences in change in several other glycemic, metabolic, and participant-reported outcomes. RESULTS: The 76 participants had a median baseline HbA1c of 8.3 (7.8, 9.1)% (67 [62-76] mmol/mol), and 61.8% were male. Compared with BGM, CGM usage was associated with significantly greater improvements in TIR (between-group difference 15.2%, 95% CI 4.6; 25.9), HbA1c (-0.9%, -1.4; -0.3 [-9.4 mmol/mol, -15.2; -3.5]), total daily insulin dose (-10.6 units/day, -19.9; -1.3), weight (-3.3 kg, -5.5; -1.1), and BMI (-1.1 kg/m2, -1.8; -0.3) and greater self-rated diabetes-related health, well-being, satisfaction, and health behavior. CONCLUSIONS: In adults with inadequately controlled insulin-treated type 2 diabetes, the 12-month impact of CGM was superior to BGM in improving glucose control and other crucial health parameters. The findings support the use of CGM in the insulin-treated subgroup of type 2 diabetes.

Influence of sphingolipid enzymes on blood glucose levels, development of diabetes, and involvement of pericytes.

AIMS: Sulfatide is a chaperone for insulin manufacturing in beta cells. Here we explore whether the blood glucose values normally could be associated with this sphingolipid and especially two of its building enzymes CERS2 and CERS6. Both T1D and T2D have low blood sulfatide levels, and insulin resistance on beta cells at clinical diagnosis. Furthermore, we examined islet pericytes for sulfatide, and beta-cell receptors for GLP-1, both of which are related to the insulin production. MATERIALS AND METHODS: We examined mRNA levels in islets from the DiViD and nPOD studies, performed genetic association analyses, and histologically investigated pericytes in the islets for sulfatide. RESULTS: Polymorphisms of the gene encoding the CERS6 enzyme responsible for synthesising dihydroceramide, a precursor to sulfatide, are associated with random blood glucose values in non-diabetic persons. This fits well with our finding of sulfatide in pericytes in the islets, which regulates the capillary blood flow in the islets of Langerhans, which is important for oxygen supply to insulin production. In the islets of newly diagnosed T1D patients, we observed low levels of GLP-1 receptors; this may explain the insulin resistance in their beta cells and their low insulin production. In T2D patients, we identified associated polymorphisms in both CERS2 and CERS6. CONCLUSIONS: Here, we describe several polymorphisms in sulfatide enzymes related to blood glucose levels and HbA1c in non-diabetic individuals. Islet pericytes from such persons contain sulfatide. Furthermore, low insulin secretion in newly diagnosed T1D may be explained by beta-cell insulin resistance due to low levels of GLP-1 receptors.

Accuracy of intermittently scanned continuous glucose monitoring during caesarean delivery in pregnant women with insulin-treated diabetes.

AIM: Continuous Glucose Monitoring (CGM) systems are not currently recommended to guide intrapartum glucose and insulin infusion, due to insufficient data. In this study, intrapartum accuracy of intermittently scanned CGM (isCGM), compared to simultaneously measured capillary glucose (CG), was evaluated. METHODS: Paired isCGM (Freestyle Libre 2) - CG data during caesarean delivery in pregnant women with insulin-treated diabetes were prospectively collected. The isCGM accuracy was assessed by MARD and Clarke Error Grid analysis. Moreover, the impact on intrapartum management was evaluated. RESULTS: Sixty-eight paired isCGM-CG data of 19 women were evaluated. The overallMARD was 9.28 %. All values were in A and B zones of Clarke Error Grid. Forty-six (68 %) isCGM-CG pairs were in the same glycemic range, meaning the same intrapartum management. All discordant data were identified by checking CG in case of isCGM above 110 mg/dL or less than 70 mg/dL [chi-square 21.76, p < 0.001]. At ROC curve, isCGM above 110 mg/dL was associated with 100 % sensitivity to discordant result at CG (AUC 0.859, p < 0.001). CONCLUSION: The accuracy of isCGM during caesarean delivery was good, particularly for glucose values between 70 and 110 mg/dL, when CG confirmation could be safely avoided.

Estimated Sustainable Cost-Based Prices for Diabetes Medicines.

Importance: The burden of diabetes is growing worldwide. The costs associated with diabetes put substantial pressure on patients and health budgets, especially in low- and middle-income countries. The prices of diabetes medicines are a key determinant for access, yet little is known about the association between manufacturing costs and current market prices. Objectives: To estimate the cost of manufacturing insulins, sodium-glucose cotransporter 2 inhibitors (SGLT2Is), and glucagonlike peptide 1 agonists (GLP1As), derive sustainable cost-based prices (CBPs), and compare these with current market prices. Design, Setting, and Participants: In this economic evaluation, the cost of manufacturing insulins, SGLT2Is, and GLP1As was modeled. Active pharmaceutical ingredient cost per unit (weighted least-squares regression model using data from a commercial database of trade shipments, data from January 1, 2016, to March 31, 2023) was combined with costs of formulation and other operating expenses, plus a profit margin with an allowance for tax, to estimate CBPs. Cost-based prices were compared with current prices in 13 countries, collected in January 2023 from public databases. Countries were selected to provide representation of different income levels and geographic regions based on the availability of public databases. Main Outcomes and Measures: Estimated CBPs; lowest current market prices (2023 US dollars). Results: In this economic evaluation of manufacturing costs, estimated CBPs for treatment with insulin in a reusable pen device could be as low as $96 (human insulin) or $111 (insulin analogues) per year for a basal-bolus regimen, $61 per year using twice-daily injections of mixed human insulin, and $50 (human insulin) or $72 (insulin analogues) per year for a once-daily basal insulin injection (for type 2 diabetes), including the cost of injection devices and needles. Cost-based prices ranged from $1.30 to $3.45 per month for SGLT2Is (except canagliflozin: $25.00-$46.79) and from $0.75 to $72.49 per month for GLP1As. These CBPs were substantially lower than current prices in the 13 countries surveyed. Conclusions and Relevance: High prices limit access to newer diabetes medicines in many countries. The findings of this study suggest that robust generic and biosimilar competition could reduce prices to more affordable levels and enable expansion of diabetes treatment globally.

Antidiabetic drug administration prevents bone mineral density loss: Evidence from a two-sample Mendelian randomization study.

The aim of this study was to investigate the effect of common antidiabetic drugs on BMD by two-sample Mendelian randomization (MR). The single nucleotide polymorphisms that were strongly associated with insulin, metformin, rosiglitazone and gliclazide were extracted as instrumental variables (IVs) for MR analysis. The inverse variance weighted (IVW) method was used as the primary MR method to assess the causal effect of antidiabetic drugs on BMD, and other MR methods, including Weighted median, MR Egger and Weighted mode, were used for complementary analysis. Reliability and stability were assessed by the leave-one-out test. In the present work, IVW estimation of the causal effect of insulin on heel BMD demonstrated that there was a null effect of insulin on heel BMD (ß = 0.765; se = 0.971; P = 0.430), while metformin treatment had a positive effect on heel BMD (ß = 1.414; se = 0.460; P = 2.118*10-3). The causal relationship between rosiglitazone and heel BMD analysed by IVW suggested that there was a null effect of rosiglitazone on heel BMD (ß = -0.526; se = 1.744; P = 0.763), but the causal effect of gliclazide on heel BMD evaluated by IVW demonstrated that there was a positive effect of gliclazide on heel BMD (ß = 2.671; se = 1.340; P = 0.046). In summary, the present work showed that metformin and gliclazide have a role in reducing BMD loss in patients with diabetes and are recommended for BMD loss prevention in diabetes.

Landscape of pharmacogenetic variants associated with non-insulin antidiabetic drugs in the Indian population.

INTRODUCTION: Genetic variants contribute to differential responses to non-insulin antidiabetic drugs (NIADs), and consequently to variable plasma glucose control. Optimal control of plasma glucose is paramount to minimizing type 2 diabetes-related long-term complications. India's distinct genetic architecture and its exploding burden of type 2 diabetes warrants a population-specific survey of NIAD-associated pharmacogenetic (PGx) variants. The recent availability of large-scale whole genomes from the Indian population provides a unique opportunity to generate a population-specific map of NIAD-associated PGx variants. RESEARCH DESIGN AND METHODS: We mined 1029 Indian whole genomes for PGx variants, drug-drug interaction (DDI) and drug-drug-gene interactions (DDGI) associated with 44 NIADs. Population-wise allele frequencies were estimated and compared using Fisher's exact test. RESULTS: Overall, we found 76 known and 52 predicted deleterious common PGx variants associated with response to type 2 diabetes therapy among Indians. We report remarkable interethnic differences in the relative cumulative counts of decreased and increased response-associated alleles across NIAD classes. Indians and South Asians showed a significant excess of decreased metformin response-associated alleles compared with other global populations. Network analysis of shared PGx genes predicts high DDI risk during coadministration of NIADs with other metabolic disease drugs. We also predict an increased CYP2C19-mediated DDGI risk for CYP3A4/3A5-metabolized NIADs, saxagliptin, linagliptin and glyburide when coadministered with proton-pump inhibitors (PPIs). CONCLUSIONS: Indians and South Asians have a distinct PGx profile for antidiabetes drugs, marked by an excess of poor treatment response-associated alleles for various NIAD classes. This suggests the possibility of a population-specific reduced drug response in atleast some NIADs. In addition, our findings provide an actionable resource for accelerating future diabetes PGx studies in Indians and South Asians and reconsidering NIAD dosing guidelines to ensure maximum efficacy and safety in the population.

Clues to the Design of Aggregation-Resistant Insulin from Proline Scanning of Highly Amyloidogenic Peptides Derived from the N-Terminal Segment of the A-Chain.

Insulin aggregation poses a significant problem in pharmacology and medicine as it occurs during prolonged storage of the hormone and in vivo at insulin injection sites. We have recently shown that dominant forces driving the self-assembly of insulin fibrils are likely to arise from intermolecular interactions involving the N-terminal segment of the A-chain (ACC1-13). Here, we study how proline substitutions within the pilot GIVEQ sequence of this fragment affect its propensity to aggregate in both neutral and acidic environments. In a reasonable agreement with in silico prediction based on the Cordax algorithm, proline substitutions at positions 3, 4, and 5 turn out to be very effective in preventing aggregation according to thioflavin T-fluorescence-based kinetic assay, infrared spectroscopy, and atomic force microscopy (AFM). Since the valine and glutamate side chains within this segment are strongly involved in the interactions with the insulin receptor, we have focused on the possible implications of the Q → P substitution for insulin's stability and interactions with the receptor. To this end, comparative molecular dynamics (MD) simulations of the Q5P mutant and wild-type insulin were carried out for both free and receptor-bound (site 1) monomers. The results point to a mild destabilization of the mutant vis à vis the wild-type monomer, as well as partial preservation of key contacts in the complex between Q5P insulin and the receptor. We discuss the implications of these findings in the context of the design of aggregation-resistant insulin analogues retaining hormonal activity.

Lived Experience of Fully Closed-Loop Insulin Delivery in Adults with Type 1 Diabetes.

Introduction: The Closing the Loop in Adults With Type 1 Diabetes (CLEAR) randomized crossover study compared a novel fully closed-loop insulin delivery system with no carbohydrate entry or mealtime bolusing (CamAPS HX), with standard insulin pump therapy and glucose sensor in adults with type 1 diabetes and suboptimal glycemic outcomes. This qualitative substudy aimed to understand the psychosocial impact of using the fully automated system. Materials and Methods: Adults participating in the CLEAR study were invited to take part in a virtual semistructured interview after they had completed 8 weeks using the fully closed-loop system. Recruitment continued until there was adequate representation and data saturation occurred. Interviews were anonymized and transcribed for in-depth thematic analysis using an inductive-deductive approach. Study participants were also asked to complete questionnaires assessing diabetes distress, hypoglycemia confidence, and closed-loop treatment satisfaction. Results: Eleven participants (eight male and three female; age range 26-66 years) were interviewed. After an initial adjustment period, interviewees reported enjoying a reduction in diabetes burden, freed-up mental capacity, and improved mood. All were happy with overnight glycemic outcomes, with the majority reporting benefits on sleep. Although experiences of postprandial glucose outcomes varied, all found mealtimes easier and less stressful, particularly when eating out. Negatives raised by participants predominantly related to the insulin pump hardware, but some also reported increased snacking and challenges around resuming carbohydrate counting at trial closeout. Conclusions: In adults with type 1 diabetes, use of a fully closed-loop insulin delivery system had significant quality-of-life benefits and provided a welcome break from the day-to-day demands of living with diabetes. Clinical Trial Registration: NCT04977908.

A two-sample Mendelian randomization study explores metabolic profiling of different glycemic traits.

We assessed the causal relation of four glycemic traits and type 2 diabetes liability with 167 metabolites using Mendelian randomization with various sensitivity analyses and a reverse Mendelian randomization analysis. We extracted instruments for fasting glucose, 2-h glucose, fasting insulin, and glycated hemoglobin from the Meta-Analyses of Glucose and Insulin-related traits Consortium (n = 200,622), and those for type 2 diabetes liability from a meta-analysis of multiple cohorts (148,726 cases, 965,732 controls) in Europeans. Outcome data were from summary statistics of 167 metabolites from the UK Biobank (n = 115,078). Fasting glucose and 2-h glucose were not associated with any metabolite. Higher glycated hemoglobin was associated with higher free cholesterol in small low-density lipoprotein. Type 2 diabetes liability and fasting insulin were inversely associated with apolipoprotein A1, total cholines, lipoprotein subfractions in high-density-lipoprotein and intermediate-density lipoproteins, and positively associated with aromatic amino acids. These findings indicate hyperglycemia-independent patterns and highlight the role of insulin in type 2 diabetes development. Further studies should evaluate these glycemic traits in type 2 diabetes diagnosis and clinical management.

Advances in Automated Insulin Delivery with the Medtronic 780G: The Australian Experience.

Aim: To assess the real-world performance of MiniMed™ 780G for Australians with type 1 diabetes (T1D) following advanced hybrid closed loop (AHCL) activation and to evaluate the effect of changing from MiniMed 670/770G to 780G. Methods: We analyzed deidentified Carelink™ continuous glucose monitoring (CGM) data from Australian users from January 2020 to December 2022, including the proportion attaining three major consensus targets: Glucose management indicator (GMI <7.0%), time in range (TIR 70-180 mg/dL >70%), and time below range (TBR 70 mg/dL <4%). Results: Comparing 670/770G users (n = 5676) for mean ± standard deviation 364 ± 244 days with 780G users (n = 3566) for 146 ± 145 days, the latter achieved a higher TIR (72.6% ± 10.6% vs. 67.3% ± 11.4%; P < 0.001), lower time above range (TAR) (25.5% ± 10.9% vs. 30.6% ± 11.7%; P < 0.001), and lower GMI (6.9% ± 0.4% vs. 7.2% ± 0.4%; P < 0.001) without compromising TBR (1.9% ± 1.8% vs. 2.0% ± 1.8%; P = 0.0015). Of 1051 670/770G users transitioning to 780G, TIR increased (70.0% ± 10.7% to 74.0% ± 10.2%; P < 0.001), TAR decreased (28.1% ± 10.9% to 24.0% ± 10.7%; P < 0.001), and TBR was unchanged. The percentage of users attaining all three CGM targets was higher in 780G users (50.1% vs. 29.5%; P < 0.001). CGM metrics were stable at 12 months post-transition. Conclusion: Real-world data from Australia shows that a higher proportion of MiniMed 780G users meet clinical targets for CGM consensus metrics compared to MiniMed 670/770G users and glucose control was sustained over 12 months.

[Fixed ratio combinations GLP-1RA and basal insulin: literature review].

The progressive nature of type 2 diabetes mellitus leads to the need for insulin therapy in a significant proportion of patients. Very often start of insulin therapy in type 2 diabetes mellitus (T2DM) is associated with weight gain and a significant increase of hypoglycemia's risk. However, innovative options, such as fixed ratio combinations of glucagon-like peptide 1 receptor agonists (GLP-1RA) and basal insulin, minimize weight gain and hypoglycemia risks and allow a greater proportion of patients to achieve individual glycemic control goals without compromising safety parameters. This review includes a description of the randomized clinical trials, as well as the results of real clinical practice of the use of two currently existing fixed ration combinations of GLP-1RA and basal insulin - iDegLira and iGlarLixi.