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Duodenal mucosal resurfacing with a GLP-1 receptor agonist increases postprandial unconjugated bile acids in patients with insulin-dependent type 2 diabetes.
Meiring, S, Meessen, ECE, van Baar, ACG, Holleman, F, Nieuwdorp, M, Olde Damink, SW, Schaap, FG, Vaz, FM, Groen, AK, Soeters, MR, et al
American journal of physiology. Endocrinology and metabolism. 2022;(2):E132-E140
Abstract
Duodenal mucosal resurfacing (DMR) is a new endoscopic ablation technique aimed at improving glycemia and metabolic control in patients with type 2 diabetes mellitus (T2DM). DMR appears to improve insulin resistance, which is the root cause of T2DM, but its mechanism of action is largely unknown. Bile acids function as intestinal signaling molecules in glucose and energy metabolism via the activation of farnesoid X receptor and secondary signaling [e.g., via fibroblast growth factor 19 (FGF19)], and are linked to metabolic health. We investigated the effect of DMR and glucagon-like peptide-1 (GLP-1) on postprandial bile acid responses in 16 patients with insulin-dependent T2DM, using mixed meal tests performed at the baseline and 6 mo after the DMR procedure. The combination treatment allowed discontinuation of insulin treatment in 11/16 (69%) of patients while improving glycemic and metabolic health. We found increased postprandial unconjugated bile acid responses (all P < 0.05), an overall increased secondary bile acid response (P = 0.036) and a higher 12α-hydroxylated:non-12α-hydroxylated ratio (P < 0.001). Total bile acid concentrations were unaffected by the intervention. Postprandial FGF19 and 7-α-hydroxy-4-cholesten-3-one (C4) concentrations decreased postintervention (both P < 0.01). Our study demonstrates that DMR with GLP-1 modulates the postprandial bile acid response. The alterations in postprandial bile acid responses may be the result of changes in the microbiome, ileal bile acid uptake and improved insulin sensitivity. Controlled studies are needed to elucidate the mechanism linking the combination treatment to metabolic health and bile acids.NEW & NOTEWORTHY Glycemic and metabolic improvements are seen in patients with type 2 diabetes after replacing their insulin therapy with DMR and GLP-1. These changes are accompanied by changes in postprandial bile acid concentrations: increased unconjugated and secondary bile acids.
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Real-world study on the effectiveness and safety of basal insulin IDegLira in type 2 diabetic patients previously treated with multi-injective insulin therapy.
Persano, M, Nollino, L, Sambataro, M, Rigato, M, Negro, I, Marchetto, S, Paccagnella, A
European review for medical and pharmacological sciences. 2021;(2):923-931
Abstract
OBJECTIVE Achieving glycemic target is paramount to control diabetes mellitus (DM) and reduce micro-vascular and macro-vascular complications. Despite the mostly recent-developed drugs, most patients still show an above desired glycated hemoglobin (HbA1c) level due to DM complex pathophysiology, therapeutic and dietary compliance and clinical inertia in introducing or intensifying insulin therapy. To support the promising results of clinical trials on the effectiveness and safety of the degludec/liraglutide combination (IDegLira) in type 2 DM patients with C-peptide values >1 ng/ml who were previously treated with basal-bolus multiple daily-dose insulin injections. PATIENTS AND METHODS This observational, prospective and non-randomized trial enrolled type 2 DM patients referred to our outpatient clinic between January 2019 and December 2019, who were shifted from multiple daily-dose insulin injection therapy to degludec/liraglutide combination as per the physician's decision. The main assessment was HbA1c variation at 6 months from baseline. Secondary assessments included variation in fasting glycemia, routine anthropometric assessments, blood chemistry, blood pressure and patients' quality of life (measured by the Diabetes Treatment Satisfaction Questionnaire [DTSQ]), from baseline to 6 months. RESULTS HbA1c (8.4 vs. 7.4%; p<0.0001) and body weight (94.1 vs. 93 kg; p<0.0001) were significantly lower after 6 months for patients on the degludec/liraglutide combination. A similar trend was observed in fasting glycemia levels (159 vs. 125 mg/dl; p<0.0001). An improved glycemic control was achieved with degludec/liraglutide despite a reduction in total daily insulin units (42 U at 6 months vs. 22 U at baseline; p<0.0001). In addition, higher scores in the DTSQ were registered after 6 months on degludec/liraglutide (mean score: 27 vs. 20; p<0.0001). The combination therapy also proved more convenient than basal-bolus therapy in terms of costs, with an average per-patient cost difference of €-0.41±0.59/die (p<0.0001). CONCLUSIONS These real-world findings show that degludec/liraglutide seems to be more effective than basal-bolus insulin in achieving glycemic control, allowing cost sustainability and improving patient satisfaction.
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Clinical effectiveness of liraglutide on weight loss in South Koreans: First real-world retrospective data on Saxenda in Asia.
Park, JS, Kwon, J, Choi, HJ, Lee, C
Medicine. 2021;(2):e23780
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Abstract
Among Asian countries, South Korea was the first to approve liraglutide as a treatment for obesity. Thus, the clinical effectiveness of liraglutide has not been studied in Asian populations.In this study, we retrospectively analyzed obese patients [body mass index (BMI) >27 kg/m2] who were treated with liraglutide between March 2018 and March 2019 in a single clinic. Weight, BMI, HbA1c, and clinical data were collected before liraglutide treatment. Changes in body weight and composition and their relationships with clinical variables were examined at re-prescription dates within 30, 60, 90, and 180 days.A total of 169 subjects were studied. The average age was 41.5 years, and 42% of the subjects were male. The average weight was 85.2 kg, and the average BMI was 30.8 kg/m2. Weight reduction was significant (-5.5 ± 3.4 kg, 30 days: -3.2 ± 1.8 kg, 60 days: -4.5 ± 2.3 kg, 90 days: -6.3 ± 2.6 kg, 180 days: -7.8 ± 3.5 kg) during the follow-up period and increased with longer treatment time (P < .001). The percentages of subjects that showed ≥ 5% and ≥ 10% body weight reduction were 62.1% and 17.2%, respectively. In the body composition analysis, skeletal muscle weight loss was -3.56 ± 29.7%, which was significantly smaller than fat weight loss of -11.06 ± 10.4% (P = .03). Weight loss was not significantly related to age, sex, baseline BMI, baseline HbA1c, smoking status, alcohol consumption, coffee intake.In conclusion, Liraglutide treatment led to meaningful weight loss in South Korean patients, and fat mass reduction was prominent during treatment. Furthermore, liraglutide showed greater clinical effectiveness with longer treatment time.
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Effectiveness of liraglutide 3 mg for the treatment of obesity in a real-world setting without intensive lifestyle intervention.
Park, JH, Kim, JY, Choi, JH, Park, HS, Shin, HY, Lee, JM, Kim, JW, Ko, HJ, Chon, S, Kim, BK, et al
International journal of obesity (2005). 2021;(4):776-786
Abstract
OBJECTIVE We investigated the efficacy and safety of liraglutide 3 mg daily in combination with diet and exercise 2, 4, and 6 months after initiation in real-world settings in Korea. METHODS People first using liraglutide starting in 2018 were recruited from ten sites in Korea. Body weight and body mass index (BMI) were measured after 2, 4, and 6 months and compared with baseline values. RESULTS The full cohort comprised 769 participants: 672 in the 2-month group, 427 in the 4-month group, and 219 in the 6-month group. The baseline mean ± standard deviation of BMI and body weight were 32.2 ± 5.1 kg/m2, and 87.5 ± 18.8 kg, respectively. Body weight and BMI decreased after initiation of liraglutide treatment: -2.94 kg and -1.08 kg/m2 at 2 months; -4.23 kg and -1.55 kg/m2 at 4 months, and -5.14 kg and -1.89 kg/m2 at 6 months (all P < 0.001). In the 6-month cohort, 52.5% and 18.3% of subjects lost ≥5% and ≥10% of body weight, respectively. After 6 months, systolic and diastolic blood pressure decreased significantly by 3.90 and 1.93 mmHg, respectively. In those with diabetes mellitus, HbA1c and fasting glucose levels decreased significantly by 1.14% and 27.8 mg/dl, respectively. Among all participants, 27.6% experienced adverse effects, including nausea (20.8%), vomiting (5.2%), diarrhoea (2.5%), and skin rash (3.6%). Documented reasons for discontinuation of treatment were lack of effect (4.4%), adverse events (4.3%), and high cost (3.1%). CONCLUSIONS In real-world settings in Korea, daily treatment with liraglutide 3 mg was associated with clinically meaningful weight loss without serious adverse events.
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Weight Outcomes With Empagliflozin as Compared With Liraglutide in Veterans With Type 2 Diabetes Mellitus.
Grabarczyk, TR, Wissman, NK
The Annals of pharmacotherapy. 2020;(10):981-987
Abstract
BACKGROUND Glucagon-like peptide-1 agonists and sodium glucose cotransporter 2 inhibitors are associated with weight loss and improved cardiovascular outcomes, and are increasingly used in pharmacotherapy for type 2 diabetes mellitus (T2DM). OBJECTIVES To compare weight loss outcomes of empagliflozin and liraglutide in patients with T2DM and overweight/obesity not yet prescribed insulin but requiring additional pharmacotherapy to improve glycemic control. METHODS This is an observational, multisite, cohort study of veterans with T2DM prescribed liraglutide or empagliflozin. Participants were prescribed either empagliflozin or liraglutide prior to November 1, 2017, had a hemoglobin A1C (A1C) ≥7.0%, had a body mass index ≥27 kg/m2, and were not treated with insulin at baseline. The primary outcome was change in weight after 1 year using multiple regression. Secondary outcomes were the proportion achieving ≥5% weight loss and change in A1C. RESULTS Weight loss was not significantly different between groups: -2.17 kg (95% CI: -2.91 to -1.42) in the liraglutide group (n = 298) and -2.81 kg (95% CI: -3.43 to -2.20) in the empagliflozin group (n = 247; P > 0.05). After adjusting for covariates, this effect remained nonsignificant. There was no difference in change in A1C between liraglutide (-0.83%; 95% CI: -1.05% to -0.62%) and empagliflozin (-0.71%; 95% CI: -0.89% to -0.53%; P > 0.05). CONCLUSIONS AND RELEVANCE There was no significant difference in weight outcomes after 1 year in veterans treated with liraglutide versus empagliflozin. Because both medications did show modest weight loss, both remain good options for patients needing an additional medication to improve glycemic control that is at least weight neutral.
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Retrospective analysis of liraglutide and basal insulin combination therapy in Japanese type 2 diabetes patients: The association between remaining β-cell function and the achievement of the glycated hemoglobin target 1 year after initiation.
Usui, R, Sakuramachi, Y, Seino, Y, Murotani, K, Kuwata, H, Tatsuoka, H, Hamamoto, Y, Kurose, T, Seino, Y, Yabe, D
Journal of diabetes investigation. 2018;(4):822-830
Abstract
AIMS/INTRODUCTION The glucose-lowering effects of the glucagon-like peptide-1 receptor agonist, liraglutide, have been shown to rely on remaining β-cell function. However, the possible associations of remaining β-cell function with the glucose-lowering effects of liraglutide in combination with basal insulin remain unknown and warrant investigation. MATERIALS AND METHODS This was a single-center, retrospective, observational study carried out in a private hospital in Osaka, Japan. Type 2 diabetes patients who received a prescription change from insulin therapy, both multiple-dose insulin and basal insulin-supported oral therapy, to liraglutide and basal insulin combination and continued the therapy for 54 weeks without additional oral antidiabetic drugs or bolus insulin were retrospectively analyzed. RESULTS Among the 72 participants who received a prescription change from multiple-dose insulin and basal insulin-supported oral therapy to liraglutide and basal insulin combination, 57 continued the therapy for 54 weeks. Of those who continued the therapy without receiving additional oral antidiabetic drugs or bolus insulin, seven participants achieved glycated hemoglobin < 7.0% at 54 weeks, but 30 participants did not. The participants who achieved glycated hemoglobin < 7.0% at 54 weeks had a significantly higher C-peptide immunoreactivity index, a β-cell function-related index frequently used in Japanese clinical settings. The receiver operating curve analysis showed that the C-peptide immunoreactivity index cut-off value for the achievement of glycated hemoglobin <7.0% at 54 weeks is 1.103. CONCLUSIONS The current findings show that the glucose-lowering effects of liraglutide rely on remaining β-cell function, even when used with basal insulin; and suggest that liraglutide and basal insulin combination might require additional bolus insulin to fully compensate insulin insufficiency in individuals with reduced β-cell function.
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Liraglutide and cardiovascular outcomes in a real world type 2 diabetes cohort.
Mirani, M, Favacchio, G, Serone, E, Lucisano, G, Rossi, MC, Berra, CC
Pharmacological research. 2018;:270-279
Abstract
In the last years, due to new regulatory guidelines requiring a stringent documentation of cardiovascular (CV) safety of novel drugs for type 2 diabetes, cardiovascular outcomes safety trials (CVOTs) are requested. CVOTs increase the knowledge about the safety profile of the new drugs, but they have intrinsic limits that make difficult their transferability to clinical practice. For this reason, real world evidence is considered an important complement to experimental data. Among the glucagon-like peptide-1 receptor agonists, liraglutide in the LEADER CVOT demonstrated superiority in reducing the risk of major CV events (MACEs) vs. placebo. We conducted an observational, retrospective, longitudinal study based on 307 patients with T2DM treated with liraglutide under routine clinical practice conditions. Real world impact of liraglutide on metabolic control, CV risk factors, hypoglycemia and CV events was assessed. Improvements during 36 months were found in HbA1c (-1.0%; p < 0.0001), fasting blood glucose (-17.6 mg/dL; p < 0.0001), body weight (-3.2 kg; p < 0.0001), waist circumference (-1.45 cm; p = 0.004), systolic blood pressure (-10.41 mmHg; p < 0.0001), diastolic blood pressure (-3.69 mmHg; p < 0.0001), total cholesterol (-7.96 mg/dL; p =0.008) and triglycerides (-20.60 mg/dl; p = 0.01). No severe hypoglycemia occurred. Incidence of MACEs in this cohort was lower than in the LEADER study (2.59 vs. 3.4 events per 100 person-years), confirming CV safety of liraglutide even in the real world. On the other hand, a higher incidence of CV event in patients with established CV disease was documented (8.1 events per 100 person-years), in spite of the use of liraglutide. In conclusion, 36-month durability and CV safety of liraglutide were documented in a real world cohort of T2DM patients, with sustained benefits on a large array of CV risk factors.
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Interindividual differences in the clinical effectiveness of liraglutide in Type 2 diabetes: a real-world retrospective study conducted in Spain.
Gomez-Peralta, F, Lecube, A, Fernández-Mariño, A, Alonso Troncoso, I, Morales, C, Morales-Pérez, FM, Guler, I, Cadarso-Suárez, C
Diabetic medicine : a journal of the British Diabetic Association. 2018;(11):1605-1612
Abstract
AIMS: To study the response of clinical variables (HbA1c , body weight, lipid profile and blood pressure) over 24 months of liraglutide treatment in a real-world clinical setting, and to describe the evolution of HbA1c and body weight reduction in response to liraglutide treatment by employing generalized additive mixed models (GAMMs). METHODS We included people aged ≥ 18 years with Type 2 diabetes mellitus that initiated liraglutide treatment between November 2011 and May 2015. Demographic and clinical data were retrieved retrospectively over 24 months from electronic medical records with a median duration of observation of 7.0 (IQR 3.0-12.0) months. RESULTS Individuals that initiated liraglutide therapy were obese (BMI 39.1 kg/m2 ), with inadequate HbA1c (68 mmol/mol [8.4%]), blood pressure and lipid levels. Upon liraglutide treatment, HbA1c , body weight, mean systolic and diastolic blood pressure, and lipid levels decreased gradually. GAMMs demonstrated that longer treatment with liraglutide was a predictor of improved HbA1c response, whereas higher baseline HbA1c , longer Type 2 diabetes duration and treatment with insulin were predictors of worse HbA1c response. Higher baseline weight, longer treatment with liraglutide and the interaction between metformin and time were predictors of improved weight response. CONCLUSIONS In this real-world study, we showed the effectiveness of liraglutide in improving body weight, HbA1c , mean systolic and diastolic blood pressure, and lipid levels. GAMMs indicated that baseline HbA1c and weight, time of treatment with liraglutide, diabetes duration and the use of metformin or insulin are predictors of clinical response to liraglutide.
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An association between liraglutide treatment and reduction in excessive daytime sleepiness in obese subjects with type 2 diabetes.
Gomez-Peralta, F, Abreu, C, Castro, JC, Alcarria, E, Cruz-Bravo, M, Garcia-Llorente, MJ, Albornos, C, Moreno, C, Cepeda, M, Almodóvar, F
BMC endocrine disorders. 2015;:78
Abstract
BACKGROUND The main purpose of the present study is to evaluate whether treatment with long-acting human glucagon-like peptide-1 liraglutide was associated with an improvement of excessive daytime sleepiness (EDS) in obese subjects with type-2 diabetes. METHODS This single-centre retrospective study included 158 obese (body mass index [BMI] ≥ 30 kg/m(2)) adult subjects with type-2 diabetes who were initiated with liraglutide treatment at least 3 months before study inclusion. Data of the Epworth Sleepiness Scale (ESS), anthropometric parameters, glucose-control and metabolic parameters were collected at liraglutide initiation (baseline) and at months 1 and 3 after liraglutide initiation. RESULTS Significant reductions in ESS score were achieved at months 1 (-1.3 ± 2.8, p < 0.001) and 3 (-1.5 ± 3.0, p < 0.001) after liraglutide introduction. After 3 months of treatment with liraglutide, significant changes in body weight (p < 0.001), BMI (p < 0.001), waist (p < 0.001) and neck circumferences (p < 0.005), HbA1c (p < 0.001), mean blood glucose (p < 0.001), fasting plasma glucose (p < 0.001), triglycerides (p < 0.01) and total cholesterol (p < 0.001) were achieved. CONCLUSIONS After 3 months of treatment with liraglutide a significant reduction in EDS was observed in obese subjects with type-2 diabetes. Besides this, significant changes in body weight and metabolic parameters of diabetes control were also accomplished. Further investigation is required to determine whether liraglutide could improve other abnormal sleep patterns and obstructive sleep apnoea.