Semaglutide trials in diabetic cohorts utilized the 1.0

The gap

Evidence profile

Sourced from the limitations and recommendations and future work of the source papers, classified as general, spanning 3 journals.

Supporting evidence — 3 representative gaps

• Tirzepatide vs. semaglutide for obesity, glycemic control, and cardiovascular outcomes: a narrative review of clinical trials (2026) · Frontiers in Medicine · doi

  semaglutide trials in diabetic cohorts utilized the 1.0 mg dosage rather than the 2.4 mg dosage approved for obesity, inherently skewing relative efficacy assessments (21, 22). Furthermore, trials exhibited significant variations intensity of lifestyle interventions, and background pharmacotherapy (4–7, 22, 23). Older subjects, non-White ethnic groups, and those with severe comorbidities are under-represented, which may limit the findings to real-world populations (24). the generalizability of in duration, titration rates Both therapies exhibit favorable and comparable safety profiles, primarily characterized by transient gastrointestinal adverse events (4–7, 22, 25). However, discontinuation in real-world settings and submaximal significantly influence both real-world tolerability and sustained clinical effectiveness (26– 28). Furthermore, recent withdrawal studies reveal significant weight regain following the cessation of therapy, highlighting the necessity for research focused on long-term maintenance strategies (25, 29).

  generallimitationsevidence 5/5
  Keywords: signi real world trials dosage cant semaglutide diabetic cohorts utilized rather approved obesity inherently skewing
• From obesity to healthy longevity: a consensus-based clinical framework for diagnosis, staging, and treatment (2026) · Frontiers in Aging · doi

  This statement has several limitations. As a consensus rely partly on expert document, agreement where high-certainty evidence is limited, particularly in areas such as optimal follow-up intervals, sequencing strategies after pharmacotherapy failure, and patient selection thresholds for surgery at lower BMI levels. Additionally, rapid therapeutic advances in obesity pharmacotherapy may necessitate periodic updates as new trial data emerge. Although this consensus the Delphi panel emphasizes a multidisciplinary approach, health consisted professionals, including dietitians and psychologists, were not formally included in the voting panel. This reflects the current structure of obesity care in Croatia, where diagnostic and pharmacological decisions are primarily physician-led. However, this represents a limitation, and future consensus processes should incorporate a broader range of healthcare professionals to enhance multidisciplinary integration. Nevertheless, use of a structured Delphi process and explicit evidence grading strengthens methodological rigor and transparency. Furthermore, economic analyses specific to Central and Eastern European healthcare systems remain limited and warrant further investigation. physicians. Allied of Future directions in obesity management are likely to include treatment combination pharmacotherapy, precision-targeted selection based on phenotyping, integration of digital health tools for monitoring and behavioral support, and expansion of preventive strategies in earlier disease stages. Establishment of national registries and longitudinal outcome monitoring will be essential for evaluating real-world effectiveness, safety, and cost-efficiency of interventions. Continued research is also needed to refine staging systems, identify predictors of treatment response, and optimize care for special populations such as older adults and individuals with multimorbidity.

  generalrecommendationsevidence 5/5
  Keywords: consensus pharmacotherapy obesity evidence limited strategies selection delphi panel multidisciplinary health professionals care future healthcare
• Long-Term Clinical Outcomes and Real-World Effectiveness of Tirzepatide in Adults With Overweight or Obesity: A Systematic Review (2026) · Cureus · doi

  The SURMOUNT clinical programme has demonstrated substantial progress; however, critical questions remain regarding the long-term use of tirzepatide for obesity management. Current evidence indicates that tirzepatide produces sustained weight loss, improves cardiovascular and metabolic health, and maintains a favourable safety profile for up to three years. Nevertheless, the durability of these benefits beyond five years remains uncertain. Future long-term studies should assess treatment adherence, persistence of weight loss, effects on cardiovascular and renal health, long-term safety, and therapeutic effectiveness across diverse patient populations. Such evidence will clarify whether the improvements observed in clinical trials translate into sustained reductions in obesity-related morbidity, mortality, and healthcare utilisation. Future research should aim to identify predictors of individual treatment response, thereby facilitating more personalised approaches to obesity management. Evidence indicates that tirzepatide is effective in individuals both with and without type 2 diabetes, across various ethnicities and ages of obesity onset, and among those using weight-promoting medications [6,15-18,40-42]. However, variability in treatment response persists. Integrating data on clinical characteristics, metabolic profiles, genetics, and behavioural factors and leveraging digital health technologies may enable clinicians to tailor therapies, enhance adherence, and optimise outcomes while efficiently utilising healthcare resources. Advances in artificial intelligence and data analytics may further support personalised decision-making and the development of improved anti-obesity therapies. Comparative studies evaluating tirzepatide against emerging anti-obesity agents and established interventions such as bariatric surgery are also warranted. The SURMOUNT-5 trial demonstrated that tirzepatide resulted in greater weight loss than semaglutide 2.4 mg [29]; however, additional head-to-head comparisons with other novel pharmacotherapies, combination regimens, and integrated medical-surgical approaches are necessary. These investigations should extend beyond weight loss to include cardiovascular outcomes, treatment persistence, patient-reported experiences, quality of life, cost-effectiveness, and long- term safety. Such comprehensive data will inform clinical and policy decision-making. As more research becomes available, it is important to examine how tirzepatide affects other health problems linked to obesity. Early studies suggest it may help with sleep apnoea, fatty liver disease, cardiovascular risk factors, and the development of type 2 diabetes [15-19,31-37]. However, more long-term studies are needed to determine whether these benefits translate into fewer serious cardiovascular events, slower kidney disease progression, better liver health, fewer hospital stays, less disability, and a lower risk of early death. These outcomes are now seen as better measures of long-term success than weight loss alone. Future investigations should also address the sustainable integration of effective anti-obesity pharmacotherapies into routine healthcare delivery. Previous research has demonstrated that establishing efficacy is insufficient; considerations of cost, accessibility, and long-term value are equally important [47]. As global demand for pharmacological obesity treatments increases, studies evaluating cost-effectiveness, treatment adherence, equity of access, and optimal care delivery models will be critical for informing policy and ensuring broad availability of these therapies. In summary, future research should not only establish the efficacy of tirzepatide but also determine optimal strategies for its long-term use in obesity management. Integrating investigations of pharmacological mechanisms, comparative effectiveness, real-world implementation, personalised medicine approaches, and economic analyses will be essential to maximising benefits for patients and public health.

  generalfuture workevidence 5/5
  Keywords: obesity long term tirzepatide weight health loss cardiovascular treatment clinical future effectiveness management evidence safety

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