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OBJECTIVE: An improvement of type 2 diabetes treatment is represented by the recent availability of a fixed-ratio combination of slow insulin degludec and GLP-1 RA liraglutide (IDegLira), which shows encouraging clinical trial results. This work represents a real-world evidence study to evaluate if the obtained clinical results are also confirmed in the clinical practice, in an Italian type 2 diabetes patients’ population. PATIENTS AND METHODS: This retrospective observational study was conducted in the Diabetology Service of the Umbria local sanitary agency (USL Umbria 1) in Perugia. The study investigated all diabetic patients >18 years, who underwent anti-diabetic treatment with basal insulin with or without the concomitant consumption of one or more oral anti-diabetic agent (BOT group) or GLP-1 RA or rapid-acting insulin bolus (BB group), with unsatisfactory glycemic control for either hypoglycemic episodes or weight gain. The observation period was February 2018 to April 2019. RESULTS: IDegLira results to be effective in reducing HbA1c and fasting plasma glucose, especially among GLP-1 RA and BOT subgroup. In BOT group, a statistical difference was noted from the first month of treatment, also for post-prandial glycemia. Obtained results were achieved at a moderate dose of IDegLira reported during the study, which also represents a significant reduction of the amount of basal insulin in BB patients. CONCLUSIONS: Obtained results suggest that in a real-world setting, the switch to IDegLira treatment is a valid option for patients with unsatisfactory glycemic control, or who experienced side effects such as weight gain and hypoglycemia of other insulin therapies. [ABSTRACT FROM AUTHOR]

Introduction: Efficacy and safety of the fixed ratio combination of insulin degludec and liraglutide (IDegLira) has been largely documented. However, long-term data are limited. This study aimed at describing persistence in therapy and the effectiveness at 48 months of IDegLira., Methods: We conducted an observational study based on retrospective chart review. All patients treated with IDegLira during 2018-2022 were included. Data on treatment approaches and clinical outcomes were collected at the first prescription of IDegLira (T0) and after 6, 12, 24, 36, and 48 months., Results: Overall, 156 patients (mean age 68 years, 64.1% men) started IDegLira, of whom 88 (56.4%) were previously treated with basal-oral therapy (BOT) and 68 (43.6%) with basal-bolus schemes (BB). Before starting IDegLira, 23.8% were treated with ≥ 2 oral antihyperglycemic agents in association with insulin; at T0, the proportion decreased to 3.2%. Short-acting insulin was discontinued after the first week. After 48 months, levels of HbA1c were significantly reduced by 1.34% in the BOT group and 1.07% in the BB group (p < 0.0001 in both groups). In the BOT group, FBG levels decreased by about 50 mg/dl and body weight was unchanged. In the BB group, FBG levels decreased by about 40 mg/dl and body weight was significantly reduced by an average of 7.7 kg. Five patients (3.2%) interrupted therapy with IDegLira during 48 months, and no severe hypoglycemia occurred., Conclusions: Our study emphasizes the important role of IDegLira in maintaining a good metabolic control while minimizing the risk of major hypoglycemia and weight gain in the long term. The substantial simplification of treatment schemes can increase adherence., (© 2024. The Author(s).)

Review of literature has shown an increased rate of thrombotic complications in diabetic patients with frequent episodes of hyperketonemia. However, the mechanisms by which ketosis promotes vascular disease in diabetic patients are unclear. It was the aim of this study to investigate early changes in haemostatic parameters and oxidative stress markers during the hyperketonemic status which follows the interruption of continuous subcutaneous insulin infusion (CSII) in type I diabetic patients. Eight CSII-treated type I diabetic patients underwent a 4-hour pump arrest. Blood glucose, insulin and 3-hydroxybutirate were measured to verify the metabolic response. A vein-occlusive (VO) test was performed for the determination of tPA and PAI-1 activities and their antigen levels before and after the CSII arrest. Coagulation factor VII and VIII were evaluated by one-stage PT and PTT method, respectively. TF, vWF, tPA and PAI-1 antigens were determined by ELISA, whereas tPA and PAI-1 activities using chromogenic methods. Plasma malondialdehyde (MDA) and protein carbonyl groups (PCG) levels were determined by HPLC and spectrophotometry, respectively. After the insulin deprivation phase, post-VO tPA antigen level significantly decreased (P = 0.0391), whereas TF and post-VO PAI-1 activity and antigen levels significantly increased (P = 0.0156 and P = 0.0234, respectively). Plasma MDA and PCG levels were 1.88-fold and 1.74-fold higher than baseline values, respectively. In conclusion, the impairment of the fibrinolytic potential and the increases in TF, MDA and PCG levels may enhance the risk of both arterial and venous thrombosis during ketosis. Thus, early detection of hyperketonemia in DM patients could contribute to the prevention of life-threatening vascular events.

This study was designed to establish the lower dose of effective GH replacement therapy in severe GH-deficient (GHD) adults. Whole body protein and lipid kinetics were determined in six GHD men in the basal state (B) and after 1 week of treatment with placebo (PL) or 3.3 (GH3.3) or 2 (GH2) micrograms/kg.day recombinant human GH (rhGH). The rates of whole body proteolysis, oxidation, and synthesis were estimated by infusing [1-13C]leucine (prime, 1 mg/kg; infusion rate, 1 mg/kg.h); those of lipolysis (measured in four of the six patients) were estimated by infusing [1,1,2,3,3-D5]glycerol (prime, 1.8 mumol/kg; infusion rate, 0.06 mumol/kg.min). Serum insulin-like growth factor I (IGF-I) concentrations (picograms per mL; mean +/- SE) similarly increased from the basal level (39 +/- 7) after 3.3 (108 +/- 18) or 2 (109 +/- 24) microgram/kg.day rhGH (P < 0.001 vs. basal), whereas they did not change with placebo (41 +/- 8). Leucine Ra was unaffected by the treatments. GH3.3 reduced by 30% the rate of leucine oxidation (P = 0.0069 vs. basal) and increased by 11% nonoxidative leucine disposal (P = 0.0095 vs. basal) and by 21% glycerol Ra (0.0035 vs. basal); GH2 and placebo had no significant effect. In conclusion, 1) at least 3.3 micrograms/ kg.day rhGH are required to increase whole body protein synthesis and lipolysis in male GHD adults; 2) 2 micrograms/kg.day rhGH normalize serum IGF-I concentrations, but do not modify protein and lipid metabolism; and 3) a normal serum IGF-I concentration does not guarantee that rhGH treatment is also effective on intermediate metabolism.