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Hyperglucagonemia contributes to hyperglycemia in patients with type 1 diabetes (T1D); however, novel therapeutics that block glucagon action could improve glycemic control. This phase 2 study evaluated the safety and efficacy of volagidemab, an antagonistic monoclonal glucagon receptor (GCGR) antibody, as an adjunct to insulin therapy in adults with T1D. The primary endpoint was change in daily insulin use at week 12. Secondary endpoints included changes in hemoglobin A1c (HbA1c) at week 13, in average daily blood glucose concentration and time within target range as assessed by continuous blood glucose monitoring (CGM) and seven-point glucose profile at week 12, incidence of hypoglycemic events, the proportion of subjects who achieve HbA1c reduction of ≥0.4%, volagidemab drug concentrations and incidence of anti-drug antibodies. Eligible participants (n = 79) were randomized to receive weekly subcutaneous injections of placebo, 35 mg volagidemab or 70 mg volagidemab. Volagidemab produced a reduction in total daily insulin use at week 12 (35 mg volagidemab: -7.59 units (U) (95% confidence interval (CI) -11.79, -3.39; P = 0.040 versus placebo); 70 mg volagidemab: -6.64 U (95% CI -10.99, -2.29; P = 0.084 versus placebo); placebo: -1.27 U (95% CI -5.4, 2.9)) without meeting the prespecified significance level (P

Background: Hypoglycemia rates usually increase when insulin treatment is intensified to improve glycemic control. We evaluated (post hoc) hypoglycemic rates in adult patients with type 1 diabetes (T1D) on sotagliflozin (a dual sodium-glucose cotransporter [SGLT] 1 and 2 inhibitor) in two phase 3, 52-week clinical trials (inTandem 1 and 2; NCT02384941 and NCT02421510). Materials and Methods: We analyzed rates of documented hypoglycemia (level 1, blood glucose ≥54 to

Aim: The real‐world benefits of continuous glucose monitoring (CGM) in the broad type 2 diabetes (T2D) population are not well studied. Our study evaluated the impact of CGM use on health care resource utilization over 12 months in adults with T2D. Materials and Methods: This retrospective cohort analysis used Optum's de‐identified Market Clarity data of >79 million people to evaluate CGM use in people with T2D who were treated with non‐insulin (NIT), basal insulin (BIT) and prandial insulin therapy (PIT). The primary outcomes were changes in all‐cause hospitalizations, acute diabetes‐related hospitalizations and acute diabetes‐related emergency room visits during the 6‐ and 12‐month post‐index period following transition from blood glucose monitoring to CGM. A pre‐specified subgroup analysis assessed glucose control and medication changes among people with T2D over 1 year. Results: The analysis included 74 679 adults with T2D (NIT; n = 25 269), (BIT; n = 16 264) and (PIT; n = 33 146). Significant reductions in all‐cause hospitalizations, acute diabetes‐related hospitalizations and acute diabetes‐related emergency room visits were observed in the 6‐month post‐index period that were sustained during the 6–12 month post‐index period (NIT, −10.1%, −31.0%, −30.7%; BIT, −13.9%, −47.6%, −28.2%; and PIT, −22.6%, −52.7%, −36.6%, respectively). A subgroup analysis of 6030 people showed mean glycated haemoglobin reductions at approximately 3 months, which were also sustained throughout the post‐index period: NIT, −1.1 (0.05)%; BIT, −1.1 (0.06)%; and PIT, −0.9 (0.04)%, p < 0.0001. Conclusions: CGM use in real‐life across different therapeutic regimens in adults with T2D was associated with reductions in health care resource utilization with improved glucose control over 1 year. [ABSTRACT FROM AUTHOR]

This document discusses the challenges of using glucagon-like peptide (GLP) analogs for people with type 1 diabetes (T1D). It highlights the global issue of overweight and obesity and the associated health problems. While GLP analogs have been shown to be effective in improving glucose control and weight loss in type 2 diabetes (T2D), they are not currently approved for use in T1D by the FDA. The document also addresses the difficulties of obtaining insurance coverage for GLP analogs and the high cost of these medications. It provides tips for the safe use of GLP analogs in T1D patients. Another article discusses the use of GLP analogs in T1D patients, specifically the off-label use of semaglutide and tirzepatide. The authors found that both medications resulted in significant weight loss and improved glucose control without an increased risk of severe hypoglycemia or diabetic ketoacidosis. However, there are challenges in determining the appropriate dosage and potential side effects such as gastrointestinal issues. The authors stress the importance of personalized treatment and regular communication with healthcare providers. They also note the lack of randomized controlled trials in this population. [Extracted from the article]

Introduction and Objective: Most patients with type 1 diabetes (T1D) in the United States are overweight (OW) or obese (OB), contributing to insulin resistance and suboptimal glucose control. The primary Food and Drug Administration-approved treatment for T1D is insulin, which may adversely affect weight. Tirzepatide is approved for managing type 2 diabetes, improves glucose control, facilitates weight loss, and improves cardiovascular disease outcomes. We assessed the use of tirzepatide in OW/OB subjects with T1D. Methods: This was a retrospective single-center real-world study in 62 OW/OB adult patients with T1D who were prescribed tirzepatide (treated group) and followed for 1 year. At least 3 months of use of tirzepatide was one of the inclusion criteria. Based on the inclusion criteria, this study represents 62 patients out of 184 prescribed tirzepatide. The control group included 37 OW/OB patients with T1D (computer frequency matched by age, duration of diabetes, gender, body mass index (BMI), and glucose control) who were not using any other weight-loss medications during the same period. The mean (±standard deviation [SD]) dose of weekly tirzepatide at 3 months was 5.6 ± 1.9 mg that increased to 9.7 ± 3.3 mg at 1 year. Results: The gender, mean baseline age, duration of diabetes, and glycosylated hemoglobin (HbA1c) were similar in the two groups, whereas BMI and weight were higher in the treated group. There were significantly larger declines in BMI and weight in the treated group than in controls across all time points among those in whom data were available. HbA1c decreased in the treated group as early as 3 months and was sustained through a 1-year follow-up (−0.67% at 1 year). As expected, insulin dose decreased at 3 months and throughout the study period. There were no reported hospitalizations from severe hypoglycemia or diabetic ketoacidosis. The mean glucose, time-in-range, time-above-range, SD, and coefficient of variation (continuous glucose monitoring metrics) significantly improved in the treated group. Conclusions: In this pilot (off label) study, we conclude that tirzepatide facilitated an average 18.5% weight loss (>46 pounds) and improved glucose control in OW/OB patients with T1D at 1 year. For safe use of tirzepatide in patients with T1D, we strongly recommend a large prospective randomized control trial in OW/OB patients with T1D. [ABSTRACT FROM AUTHOR]

This article provides an overview of the development and future of automated insulin delivery (AID) systems, which include insulin pumps, continuous glucose monitoring (CGM), and smart algorithms. It discusses the advancements in insulin pump technology, from the first portable pump in 1963 to the smaller, wearable pumps introduced in the 1980s and beyond. The article also explores the integration of CGM with insulin pumps and the introduction of AID systems that automatically deliver insulin based on real-time glucose data. It highlights specific AID systems, such as the MiniMed™ 670G and 780G, and the t:slim X2™ with Control-IQ technology. The document further provides an overview of various artificial pancreas systems for the management of type 1 diabetes (T1D), including the Tandem AHCL Control-IQ, OmniPod 5 HCL, Diabeloop generation 1, CamAPS FX, Tidepool Loop, and Beta Bionics iLet. It discusses the results of clinical trials and real-world data for these systems and addresses barriers to adoption, such as cost and user experience. The article concludes that the use of artificial pancreas systems improves glucose control and reduces the burden of diabetes, with the potential to prevent long-term complications. [Extracted from the article]

Introduction Type 1 diabetes (T1D) results from the chronic autoimmune-mediated destruction of insulin-producing [beta] cells within pancreatic islets (1, 2). There is a wealth of knowledge regarding the disease pathogenesis [...], Major histocompatibility (MHC) class II molecules are strongly associated with many autoimmune disorders. In type 1 diabetes (T1D), the DQ8 molecule is common, confers significant disease risk, and is involved in disease pathogenesis. We hypothesized that blocking DQ8 antigen presentation would provide therapeutic benefit by preventing recognition of self-peptides by pathogenic T cells. We used the crystal structure of DQ8 to select drug-like small molecules predicted to bind structural pockets in the MHC antigen-binding cleft. A limited number of the predicted compounds inhibited DQ8 antigen presentation in vitro, with 1 compound preventing insulin autoantibody production and delaying diabetes onset in an animal model of spontaneous autoimmune diabetes. An existing drug with a similar structure, methyldopa, specifically blocked DQ8 in patients with recent-onset T1D and reduced inflammatory T cell responses to insulin, highlighting the relevance of blocking disease-specific MHC class II antigen presentation to treat autoimmunity.