OBJECTIVEInsulin degludec/liraglutide (IDegLira) is a novel combination of insulin degludec (IDeg) and liraglutide. This trial investigated the contribution of the liraglutide component of IDegLira versus IDeg alone on efficacy and safety in patients with type 2 diabetes. RESEARCH DESIGN AND METHODSIn a 26-week, double-blind trial, patients with type 2 diabetes (A1C 7.5-10.0% [58-86 mmol/mol]) on basal insulin (20-40 units) and metformin with or without sulfonylurea/glinides were randomized (1:1) to once-daily IDegLira + metformin or IDeg + metformin with titration aiming for fasting plasma glucose between 4 and 5 mmol/L. Maximum allowed doses were 50 dose steps (equal to 50 units IDeg plus 1.8 mg liraglutide) and 50 units for IDeg. The primary end point was change in A1C from baseline. RESULTSA total of 413 patients were randomized (mean A1C 8.8% [73 mmol/mol]; BMI 33.7 kg/m 2 ). IDeg dose, alone or as part of IDegLira, was equivalent (45 units). A1C decreased by 1.9% (21 mmol/mol) with IDegLira and by 0.9% (10 mmol/mol) with IDeg (estimated treatment difference 21.1% [95% CI 21.3, 20.8], 212 mmol/mol [95% CI 214, 29; P < 0.0001). Mean weight reduction with IDegLira was 2.7 kg vs. no weight change with IDeg, P < 0.0001. Hypoglycemia incidence was comparable (24% for IDegLira vs. 25% for IDeg). Overall adverse events were similar, and incidence of nausea was low in both groups (IDegLira 6.5% vs. IDeg 3.5%). CONCLUSIONSIDegLira achieved glycemic control superior to that of IDeg at equivalent insulin doses without higher risk of hypoglycemia and with the benefit of weight loss. These findings establish the efficacy and safety of IDegLira and the distinct contribution of the liraglutide component.Basal insulin therapy, often in combination with oral agents, including metformin, is well established for the treatment of patients with type 2 diabetes. Once initiated, basal insulin is usually continued even when control is not achieved (1,2). Indeed, more than half of patients with type 2 diabetes treated with basal insulin do not achieve glycemic control (A1C #7.0% [53 mmol/mol]) (1,3,4) and are therefore at increased risk of developing diabetes complications. Delayed or suboptimal

AimTo investigate the safety and efficacy of insulin degludec/liraglutide (IDegLira), a novel combination product, as add‐on therapy for people with Type 2 diabetes uncontrolled on sulphonylurea therapy.MethodsIn this 26‐week, double‐blind trial, adults with Type 2 diabetes [HbA1c 53–75 mmol/mol (7.0–9.0%)] were randomized to IDegLira (n = 289) or placebo (n = 146) as add‐on to pre‐trial sulphonylurea ± metformin, titrating to a fasting glycaemic target of 4.0–6.0 mmol/l. Treatment initiation was at 10 dose steps, and maximum dose was 50 dose steps (50 units insulin degludec/1.8 mg liraglutide).ResultsThe mean HbA1c decreased from 63 mmol/mol (7.9%) to 46 mmol/mol (6.4%) with IDegLira and to 57 mmol/mol (7.4%) with placebo [estimated treatment difference –11 mmol/mol (95% CI –13; –10) or –1.02% (95% CI –1.18; –0.87); P < 0.001]. The HbA1c target of 53 mmol/mol (<7%) was achieved by 79.2% of participants in the IDegLira group vs 28.8% in the placebo group [estimated odds ratio 11.95 (95% CI 7.22; 19.77); P < 0.001]. Mean weight change was +0.5 kg with IDegLira vs –1.0 kg with placebo [estimated treatment difference 1.48 kg (95% CI 0.90; 2.06); P < 0.001]. Confirmed hypoglycaemia occurred in 41.7 and 17.1% of IDegLira‐ and placebo‐treated participants, respectively, with rates of 3.5 vs 1.4 events/patient‐years of exposure [estimated rate ratio 3.74 (95% CI 2.28; 6.13); P < 0.001]. IDegLira was generally well tolerated. The rates of serious adverse events were 20.3 and 8.0 per 100 patient‐years of exposure with IDegLira and placebo, respectively, without obvious patterns in the type of events.Conclusions IDegLira can be used in people uncontrolled with sulphonylurea ± metformin to improve efficacy with a safety profile in line with previous DUAL trials.

BACKGROUND Diabetes rates among pregnant women in the United States have been increasing and are associated with adverse pregnancy outcomes. AIM To investigate differences in birth outcomes (preterm birth, macrosomia, and neonatal death) by diabetes status. METHODS Cross-sectional design, using linked Missouri birth and death certificates (singleton births only), 2010 to 2012 ( n = 204057). Exposure was diabetes (non-diabetic, pre-pregnancy diabetes-insulin dependent (PD-I), pre-pregnancy diabetes-non-insulin dependent (PD-NI), gestational diabetes- insulin dependent (GD-I), and gestational diabetes-non-insulin dependent (GD-NI)]. Outcomes included preterm birth, macrosomia, and infant mortality. Confounders included demographic characteristics, adequacy of prenatal care, body mass index, smoking, hypertension, and previous preterm birth. Bivariate and multivariate logistic regression assessed differences in outcomes by diabetes status. RESULTS Women with PD-I, PD-NI, and GD-I remained at a significantly increased odds for preterm birth (aOR 2.87, aOR 1.77, and aOR 1.73, respectively) and having a very large baby [macrosomia] (aOR 3.01, aOR 2.12, and aOR 1.96, respectively); in reference to non-diabetic women. Women with GD-NI were at a significantly increased risk for macrosomia (aOR1.53), decreased risk for their baby to die before their first birthday (aOR 0.41) and no difference in risk for preterm birth in reference to non-diabetic women. CONCLUSION Diabetes is associated with the poor birth outcomes. Clinical management of diabetes during pregnancy and healthy lifestyle behaviors before pregnancy can reduce the risk for diabetes and poor birth outcomes.

Objectives: This study aims to evaluate the impact of Microburst Insulin Infusion (MII) treatment on Type 1 and 2 diabetic patients' HbA1c, lipids, peripheral neuropathy, and patient-reported health status.Methods: We reviewed clinical charts, including lab results, for more than 80 diabetic and pre-diabetic patients treated at one U.S. outpatient clinic in St. Louis, Missouri between February 2017 and December 2019. Data included patient demographics, treatment data, lab and neuropathy tests, and self-reported patient health status questions.The explanatory variable was number of months of MII treatment. Treatments are 3–4 h in length, with two intensive infusions the first week and one treatment each week thereafter, usually for 12 weeks total. Lab tests were at 12-week intervals.Generalized linear modeling and t-tests assessed the significance of differences between patients' baseline lab values, neuropathy measures, and health status before treatment vs. after final treatment.Results: Number of MII treatments per patient ranged from 1 to 262, over 1–24 months. Time in MII treatment was significantly associated with reductions in HbA1c by nearly 0.04 points per month, and triglycerides declined 3 points per month. Neuropathy measures of large toe vibratory sensation (clanging tuning fork) improved significantly, as did patient-reported health and feelings of improvement since beginning treatment.Discussion: The MII therapy appears to be efficacious in treating diabetic patients, particularly those with complications like neuropathy. Our findings affirmed several other studies. We uniquely incorporated patient health questionnaires, and empirically studied MII treatment efficacy for diabetes in a population large enough to permit statistically valid inferences. With multiple waves of data for over 80 patients, this is one of the most extensive quantitative studies of microburst insulin infusion therapy conducted to date, with protocols more uniformly implemented and survey instruments more consistently administered by the same clinical team. Given the advances in insulin infusion therapy brought by MII, and early indications of its efficacy, the time is right for more in-depth studies of the outcomes patients can achieve, the physiological mechanisms by which they occur, MII's comparative effectiveness vis-à-vis traditional treatments, and cost-effectiveness.

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