Once-Weekly Insulin Icodec With Dosing Guide App Versus Once-Daily Basal Insulin Analogues in Insulin-Naive Type 2 Diabetes (ONWARDS 5) : A Randomized Trial.

BACKGROUND: Inadequate dose titration and poor adherence to basal insulin can lead to suboptimal glycemic control in persons with type 2 diabetes (T2D). Once-weekly insulin icodec (icodec) is a basal insulin analogue that is in development and is aimed at reducing treatment burden. OBJECTIVE: To compare the effectiveness and safety of icodec titrated with a dosing guide app (icodec with app) versus once-daily basal insulin analogues (OD analogues) dosed per standard practice. DESIGN: 52-week, randomized, open-label, parallel-group, phase 3a trial with real-world elements. (ClinicalTrials.gov: NCT04760626). SETTING: 176 sites in 7 countries. PARTICIPANTS: 1085 insulin-naive adults with T2D. INTERVENTION: Icodec with app or OD analogue (insulin degludec, insulin glargine U100, or insulin glargine U300). MEASUREMENTS: The primary outcome was change in glycated hemoglobin (HbA1c) level from baseline to week 52. Secondary outcomes included patient-reported outcomes (Treatment Related Impact Measure for Diabetes [TRIM-D] compliance domain score and change in Diabetes Treatment Satisfaction Questionnaire [DTSQ] total treatment satisfaction score). RESULTS: The estimated mean change in HbA1c level from baseline to week 52 was greater with icodec with app than with OD analogues, with noninferiority (P < 0.001) and superiority (P = 0.009) confirmed in prespecified hierarchical testing (estimated treatment difference [ETD], -0.38 percentage points [95% CI, -0.66 to -0.09 percentage points]). At week 52, patient-reported outcomes were more favorable with icodec with app than with OD analogues (ETDs, 3.04 [CI, 1.28 to 4.81] for TRIM-D and 0.78 [CI, 0.10 to 1.47] for DTSQ). Rates of clinically significant or severe hypoglycemia were low and similar with both treatments. LIMITATION: Inability to differentiate the effects of icodec and the dosing guide app. CONCLUSION: Compared with OD analogues, icodec with app showed superior HbA1c reduction and improved treatment satisfaction and compliance with similarly low hypoglycemia rates. PRIMARY FUNDING SOURCE: Novo Nordisk A/S.

Association of skin autofluorescence and carotid intima-media thickness in acromegaly patients.

BACKGROUND: The Pituitary Tumors Centers of Excellence (PTCOE) concept was established to provide a multimodal approach with careful management of comorbidities. Acromegaly, one of the main concerns of PTCOE per se, leads to increased mortality rates of which cardiovascular disease is an important cause. Increased skin autofluorescence (SAF) was shown to be associated with carotid intima-media thickness (CIMT), a well-established marker of atherosclerosis, and consequently cardiovascular complications. This study aimed to evaluate SAF and CIMT in association with anthropometric, clinical, and biochemical parameters in acromegaly patients and healthy controls. METHODS: The study group included 138 acromegaly patients and 127 healthy controls from the Department of Endocrinology and Metabolism Disease, Marmara University Medical School. Growth hormone, insulin-like growth factor I, lipids, glucose, insulin levels were assessed. Advanced glycation end products (AGEs) were measured by the auto-fluorescence reader. CIMT was measured from the common carotid artery wall on B-mode ultrasound. RESULTS: CIMT and SAF levels were significantly higher in the acromegaly group than the control group. There was a positive correlation between SAF and CIMT both in the total cohort and acromegaly patients. The presence of acromegaly, age, and SAF were the determining factors of CIMT in the whole study cohort. CONCLUSIONS: Our study is the first to examine the relationship between SAF and CIMT in acromegaly patients. We found higher CIMT and enhanced SAF in the acromegaly group compared to the control group with a significant positive correlation in between. The presence of acromegaly was related to increased SAF levels and CIMT. SAF was associated with CIMT in acromegaly patients. Implementation of CIMT and SAF evaluation in this clinical setting may improve cardiovascular complications, particularly in the PTCOE.

Glycemic Control and Prevention of Diabetic Complications in Low- and Middle-Income Countries: An Expert Opinion.

INTRODUCTION: Trends on glycemic control and diabetes complications are known for high-income countries, but comprehensive data from low- and middle-income countries (LMIC) are lacking. METHODS: This is an expert opinion based on two retrospective studies. Here we examine the recent subset analysis of relevant data from the IDMPS Wave 7 (International Diabetes Management-Practices Study, 2015-2016) and the GOAL study conducted in multiple LMICs. RESULTS: Wave 7 sub-analysis was performed in 6113 people with type 2 diabetes from 24 LMIC. Poorly controlled diabetes (hemogloblin A1c [HbA1c] ≥ 7%) was found in 58.6, 73.0 and 78.3% of participants with diabetes duration of < 5, 5-12 and > 12 years, respectively (in association with a high prevalence of macro- and microvascular complications). Moreover, 37.7% of participants with diabetes duration of 5-12 years were treated only with oral antihyperglycemic drugs. The GOAL study investigated the efficacy of insulin in 2704 poorly controlled participants (mean HbA1c 9.7%; diabetes duration 10.1 ± 6.7 years; 10 LMIC). A significant 2% reduction in mean HbA1c levels was observed after 12 months of treatment. Only 7.2% of participants experienced a symptomatic episode of hypoglycemia (nocturnal or severe hypoglycemia events were infrequent). CONCLUSION: The rate of well-controlled participants (HbA1c < 7.0%) in the Wave 7 sub-analysis was lower than that observed in the USA (NHANES survey) or in European countries (GUIDANCE study), and the incidence of microvascular complications was higher. The GOAL study showed that insulin treatment improves glycemic control and reduces this gap. The Expert Panel recommends intensifying diabetes treatment as soon as possible, as well as patients' education and other preventive measures, initiatives which require modest costs compared to hospitalization and treatment of diabetes complications.