Liraglutide

OBJECTIVE: We aimed to compare the effectiveness and safety of semaglutide 1.0 mg versus dulaglutide 1.5 mg and liraglutide 1.8 mg in patients with type 2 diabetes mellitus (T2DM) under routine clinical care. METHODS: This multicenter, retrospective, real-world study enrolled Chinese adults with T2DM who initiated GLP-1 receptor agonist therapy in endocrinology clinics between January 1, 2022, and August 31, 2024. We compared the effectiveness of these agents on HbA1c and weight loss, with safety as a key exploratory endpoint. Additionally, the UK Prospective Diabetes Study Outcomes Model 2.1 was utilized to project long-term health outcomes. RESULTS: This multicenter retrospective study included 111, 74, and 107 patients treated with semaglutide 1.0 mg, dulaglutide 1.5 mg, and liraglutide 1.8 mg, respectively. After 1:1 propensity score matching, semaglutide demonstrated significantly greater HbA1c reduction compared to both dulaglutide (-0.27% ± 0.70%, p = 0.008) and liraglutide (-0.39% ± 0.87%, p < 0.001), along with higher glycemic target achievement rates. Semaglutide was associated with improved outcomes in all death, cardiovascular death, and other death endpoints. No significant differences in safety profiles were observed among the three treatment groups. CONCLUSIONS: Semaglutide demonstrated superior glycemic control and weight loss compared to both dulaglutide and liraglutide, whereas dulaglutide and liraglutide exhibited comparable clinical efficacy.

BACKGROUND: Incretin analogues, used for the treatment of type 2 diabetes mellitus and obesity, such as GLP1-receptor agonist liraglutide (Lira) have been shown to reduce major adverse cardiac events in recent clinical trials of heart failure. Tirzepatide (TZP), a dual GIP/GLP1-receptor agonist has shown promising results in the SUMMIT trial as improved cardiovascular outcomes in patients with heart failure with preserved ejection fraction (HFpEF). However, data regarding their use in heart failure with reduced ejection fraction (HFrEF) is lacking. We performed a head-to-head comparative study in a mouse model of non-ischaemic cardiac injury induced by continuous angiotensin II (AngII) infusion, as AngII is a key driver of both heart failure forms. METHODS: Osmotic minipumps were inserted for subcutaneous (s.c.) administration of AngII (1.5 mg/kg/day) in 5-month-old male Balb/c mice or sham surgery was performed. Animals were treated with vehicle (Veh), Lira (300 µg/day i.p.) or TZP (48 µg/day s.c.) for 14 days in the following groups: Sham/Veh (n = 7), AngII/Veh (n = 15), Sham/Lira (n = 7), AngII/Lira (n = 15), Sham/TZP (n = 8), AngII/TZP (n = 15). Cardiac structural, functional and molecular characteristics were assessed by echocardiography, ECG, immunohistochemistry, flow cytometry and qRT-PCR. RESULTS: Mortality was significantly higher in AngII/Veh animals compared to controls, while AngII/TZP mice showed significantly reduced mortality after 14 days of treatment. Both Lira and TZP caused significant weight reduction compared to controls. AngII given alone also reduced body mass, and this reduction was further enhanced by TZP. Treatment with both compounds preserved cardiac systolic and diastolic function compared with AngII/Veh animals, as shown by normal ejection fraction and E/e', respectively. Both Lira and TZP decreased the AngII-induced elevation of cardiac fibrosis and hypertrophy markers, including Ctgf, Col1a1, Col3a1, and Nppa, while TZP also reduced the elevated Nppb level. TZP also reduced systemic inflammation, as shown by the reduction in serum CRP levels. CONCLUSIONS: Lira and TZP preserved cardiac function and decreased markers of hypertrophy and fibrosis in mice with AngII-induced heart failure, whereas TZP also significantly decreased mortality. In addition to HFpEF, the use of incretin analogues may also be of clinical relevance in the treatment of HFrEF. However, as patients with heart failure, AngII level is elevated and can cause weight loss/cachexia, the usage of incretin analogues to treat non-obese heart failure patients should be considered.

BACKGROUND: Glucagon-like peptide-1 receptor agonists and their analogues have emerged as effective pharmacotherapies for obesity. OBJECTIVE: To assess the short-term cost-effectiveness of subcutaneous tirzepatide, semaglutide, liraglutide, and oral semaglutide for managing obesity or overweight in patients without diabetes. METHODS: A decision tree model was developed using a 68-week time window with consideration of serious adverse events and treatment discontinuation from a US payer's perspective. The study population were adults with obesity or overweight with at least 1 weight-related comorbidity but without diabetes. Clinical data were obtained from clinical trials. Model utilities, disutilities, and the costs of serious adverse events were sourced from published literature. Medication costs were assigned from Red Book. All costs were calculated in 2024 US dollars. The incremental cost-effectiveness ratio was calculated based on the cost per quality-adjusted life-year (QALY) gained. A willingness-to-pay threshold of $150,000 per QALY was used. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the effect of parameter uncertainty on the results. RESULTS: In the base-case analysis, both subcutaneous tirzepatide and oral semaglutide were cost-effective vs subcutaneous liraglutide and subcutaneous semaglutide. Compared with oral semaglutide, subcutaneous tirzepatide was cost-effective, with an incremental cost-effectiveness ratio of $34,212 per QALY gained. Sensitivity analyses indicated the results were highly sensitive to medication costs and the effectiveness of medications. The probabilistic sensitivity analysis suggested that subcutaneous tirzepatide was most likely to remain cost-effective, with a 98% probability at a willingness to pay of $150,000 per QALY compared with other medications. CONCLUSIONS: Subcutaneous tirzepatide and oral semaglutide were cost-effective therapies compared with subcutaneous liraglutide and subcutaneous semaglutide for the short-term management of obesity in adults without diabetes. At or under a willingness-to-pay threshold of $150,000 per QALY, subcutaneous tirzepatide was most cost-effective, surpassing oral semaglutide. These findings provide valuable insights for health care decision-makers in selecting antiobesity medications.

OBJECTIVE: This prospective study aimed to describe the clinical course in terms of glycemic outcomes, body weight, and adverse events during the first 12 weeks following a switch from glucagon-like peptide-1 receptor agonists (GLP-1 RAs) directly to tirzepatide 5 mg. METHODS: Participants were ≥18 years with type 2 diabetes (T2D), glycated hemoglobin (HbA1c) ≥6.5% to ≤9.0%, body mass index ≥25 kg/m2 and were on a stable treatment dose of GLP-1 RAs (liraglutide every day [1.2, 1.8 mg], semaglutide once-weekly [0.5, 1.0, 2.0 mg], or dulaglutide once-weekly [0.75, 1.5, 3.0, and 4.5 mg]) for ≥3 months at baseline. The primary end point was HbA1c change from baseline at week 12. Secondary end points included change from baseline in fasting serum glucose, body weight, and glucose assessed by continuous glucose monitoring. Safety was also assessed. RESULTS: Participants were 58.3 years on average, with baseline HbA1c 7.39%, body mass index 35.18 kg/m2, T2D duration around 12.4 years, and included 55% females. Semaglutide (55%) and dulaglutide (42%) were the most commonly used GLP-1 RAs at baseline with semaglutide 1.0 mg and dulaglutide 1.5 mg being the most common treatment doses. At week 12, mean HbA1c changed from baseline by -0.43%, fasting serum glucose by -7.83 mg/dL, and body weight by -2.15 kg (all P < .01). Glycemic outcomes and body weight improved in participants in all baseline GLP-1 RA subgroups. Twenty participants (13.2%) developed gastrointestinal events. Three (2%) participants discontinued tirzepatide due to adverse events. There were no severe hypoglycemic events or deaths. CONCLUSION: In this prospective study, when people with T2D on stable GLP-1 RA treatment were switched directly to tirzepatide 5 mg, they experienced improved glycemic outcomes and additional weight reduction with an acceptable risk of adverse gastrointestinal events over 12 weeks.

GLP-1 receptor agonists (GLP-1RAs) are recommended for patients with type 2 diabetes (T2D), particularly those at high cardiovascular risk. Oral semaglutide is the first oral GLP-1RA. In clinical trials, oral semaglutide 14 mg reduced mean HbA1c by approximately 1.1-1.5% and reduced body weight by up to 5 kg. These changes were significantly greater compared with empagliflozin, sitagliptin and liraglutide (p < 0.05 for estimated treatment differences at 52 weeks in patients on treatment without rescue medication use). The most common side effects were gastrointestinal, mainly mild-to-moderate and transient nausea. Oral semaglutide may change the paradigm of T2D treatment in primary care.

BACKGROUND: The role of glucagon-like peptide-1 receptor agonists (GLP1-RAs) in patients with weight regain after bariatric surgery remains unclear. The objective of this study was to determine the efficacy and safety of 12 months of GLP1-RA treatment in a real-world patient population with weight regain after bariatric surgery. METHODS: A single-centre retrospective observational study. Patients with post-bariatric weight regain subsequently treated with GLP1-RA were identified, and the effect on weight after 12 months of treatment was determined. Data are presented as medians (interquartile ranges) or frequencies (%), and Wilcoxon signed-rank tests and Mann-Whitney U tests were used for paired and nonpaired group comparisons, respectively. RESULTS: Forty patients (80% female) were included in the analysis. Liraglutide (3.0 mg, daily subcutaneous injection, n = 22) or semaglutide (1.0 mg, weekly subcutaneous injection, n = 18) was started 74.5 (51.0, 108.3) months after surgery following a weight regain of 14.7 (10.3, 19.6)%. After 12 months of GLP1-RA treatment, a total body weight, BMI, and percentage excess body weight reduction of 10.5 (6.1, 14.7) kg, 3.7 (2.5, 5.3) kg/m2, and 41.7 (22.1, 70.5)% were observed, corresponding to a loss of 99.3 (61.0, 135.4)% of the weight regained (P-value < 0.0001). The observed reduction in BMI was significantly lower with liraglutide than with semaglutide, 3.1 (2.0, 4.7) vs. 4.7 (3.7, 6.0) kg/m2 (P-value = 0.04). Adverse events were reported in 13 (32.5%) patients, all of which were mild and transient. CONCLUSION: GLP1-RA therapy with liraglutide or semaglutide for 12 months is efficacious and safe for the treatment of weight regain following bariatric surgery. CLINICAL TRIAL NUMBER: Not applicable.