Moderate · human
This multicentre retrospective observational study used TriNetX, a global healthcare data platform, to examine real-world associations between semaglutide use and survival outcomes in adults with type 2 diabetes (T2D) and chronic kidney disease (CKD). Researchers identified over 1.1 million eligible patients, of whom 14,511 initiated semaglutide and 69,700 initiated sitagliptin between 2018 and 2020. After propensity score matching to balance baseline characteristics, 13,703 patients were included in each group. The study found that the semaglutide group had a significantly lower 3-year incidence of all-cause death (7.2% vs. 9.5%) compared with the sitagliptin group. Secondary outcomes including acute heart failure, acute myocardial infarction, and stroke also favored semaglutide. The authors note these findings are consistent with the randomized FLOW trial. Key limitations include the retrospective, non-randomized design, potential for residual confounding despite propensity score matching, reliance on administrative coding data, and the inability to account for medication adherence or dosing details. Findings should be interpreted as associative, not causal.
Open heart · Jul 2025DOI ↗ Moderate · human
This systematic review and network meta-analysis evaluated the comparative efficacy and safety of dual and triple incretin-based agonists — compounds targeting combinations of GLP-1, GIP, and glucagon receptors — versus standard therapies for type 2 diabetes mellitus (T2DM). Researchers searched PubMed, Web of Science, Cochrane Library, and Embase through July 2024, identifying randomized controlled trials assessing outcomes including body weight, HbA1c, fasting blood glucose (FBG), adverse events (AEs), and serious adverse events (SAEs). The analysis found that Retatrutide (a triple agonist) was associated with the greatest weight reduction, while Tirzepatide (a dual GLP-1/GIP agonist) showed the largest reductions in both FBG and HbA1c. Regarding safety, Tirzepatide and Cotadutide were associated with increased AEs, whereas Semaglutide was associated with reduced SAEs. The authors suggest that receptor-specific targeting may help personalize T2DM treatment. Key limitations include small sample sizes in some included trials, short study durations, and reliance on indirect comparisons in the network meta-analysis. The authors acknowledge that direct head-to-head trials are needed to confirm these findings. The study was prospectively registered (PROSPERO: CRD42024532368).
Acta diabetologica · Jun 2025DOI ↗ Moderate · human
This systematic review and meta-analysis compared the weight-loss effectiveness of tirzepatide versus semaglutide in humans by searching PubMed, Scopus, and Web of Science through January 2025. From 751 initial records, seven studies were ultimately included — two randomized controlled trials (RCTs) and five retrospective cohort studies. Using a random-effects model in RStudio, the authors pooled mean differences (MDs) in body weight change between the two agents. The analysis found that tirzepatide was associated with statistically significantly greater weight loss compared to semaglutide (MD = 4.23 kg; 95% CI: 3.22–5.25). Subgroup analyses suggested that higher tirzepatide doses (>10 mg) and longer treatment durations (>6 months) were associated with progressively larger weight differences. Study quality was assessed using the Newcastle-Ottawa Scale for observational studies and the Cochrane Risk of Bias version 2 tool for RCTs; the authors reported high quality and low risk of bias overall. Publication bias was evaluated via forest plots and Egger's test. Limitations include the small number of included studies (only two RCTs), reliance on retrospective real-world data for most of the analysis, potential heterogeneity across study populations, and the possibility of residual confounding in the observational studies.
Journal of clinical medicine research · May 2025DOI ↗ Moderate · human
This systematic review and meta-analysis examined the weight-loss efficacy and safety of cagrilintide (an amylin analogue) alone and in combination with semaglutide 2.4 mg (referred to as "Cagrisema") compared to placebo or active comparators (semaglutide or liraglutide) in adults with obesity. Researchers searched electronic databases and identified 3 eligible randomized controlled trials encompassing 430 participants. The pooled analysis found that Cagrisema was associated with significantly greater percentage and absolute body weight reduction compared to semaglutide 2.4 mg alone over 20–32 weeks, though with notably high statistical heterogeneity (I² up to 98%). Cagrilintide monotherapy showed statistically similar weight loss to semaglutide or liraglutide over 26–32 weeks. Regarding safety, treatment-emergent and serious adverse events were broadly comparable across groups; however, gastrointestinal adverse events and vomiting were significantly more frequent with Cagrisema versus semaglutide, while vomiting was significantly lower with cagrilintide monotherapy versus semaglutide or liraglutide. Key limitations include the very small number of included trials (n=3), limited total sample size, short-to-medium follow-up durations, and very high heterogeneity, which tempers confidence in the pooled estimates.
Indian journal of endocrinology and metabolism · Sep 2024DOI ↗ Moderate · human
This Phase II randomised controlled trial evaluated survodutide (BI 456906), a dual glucagon receptor/GLP-1 receptor agonist, across six dose groups compared with placebo and open-label semaglutide (1.0 mg once weekly) in 413 adults with type 2 diabetes on metformin background therapy. Over 16 weeks, survodutide produced dose-dependent reductions in HbA1c and bodyweight. Higher dose groups achieved HbA1c reductions of approximately 17–19 mmol/mol (~1.6–1.7%), broadly comparable to semaglutide (~16 mmol/mol, ~1.5%), while lower doses showed smaller reductions. Bodyweight decreased dose-dependently, with the highest-dose groups producing greater reductions (up to ~8.7%) than semaglutide (~5.3%). Adverse events, predominantly gastrointestinal, were reported in ~78% of survodutide-treated participants versus ~52% in both the placebo and semaglutide groups. Limitations include the relatively short 16-week treatment duration, the open-label (non-blinded) design of the semaglutide comparator arm, and the Phase II exploratory nature of the trial, which was not powered for head-to-head superiority conclusions. The trial was funded by Boehringer Ingelheim.
Diabetologia · Dec 2023DOI ↗