Semaglutide Maintains Weight Loss Through 24 Months in Real-World Diabetic Patients — Injectable and Oral Forms Both Effective

In 175 real-world patients with type 2 diabetes and obesity, injectable semaglutide produced 15.9 kg weight loss at 24 months while oral semaglutide achieved 10.7 kg at 12 months, with both forms maintaining weight loss long-term and significantly reducing HbA1c.

Del Prete, Michela et al.·Eating and weight disorders : EWD·2025·
RPEP-106802025RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Not classified
Evidence
Not graded
Sample
Not reported

What This Study Found

**Injectable semaglutide (n=129):**

- 6 months: -10.4 kg weight, -3.9 kg/m² BMI, -1.9% HbA1c

- 12 months: -9.3 kg weight, -3.4 kg/m² BMI, -1.5% HbA1c

- 24 months: -15.9 kg weight, -5.8 kg/m² BMI, -1.5% HbA1c

**Oral semaglutide (n=46):**

- 6 months: -6.7 kg weight, -2.6 kg/m² BMI, -1.5% HbA1c

- 12 months: -10.7 kg weight, -3.9 kg/m² BMI, -0.8% HbA1c

Notably, weight loss was maintained and even continued to increase through 24 months with injectable semaglutide — contradicting concerns about weight plateau or regain during extended treatment. The oral formulation showed comparable effectiveness to injectable at 12 months despite initial slower weight loss.

Key Numbers

How They Did This

Retrospective real-world study of 175 patients with type 2 diabetes and obesity/overweight treated with injectable semaglutide (n=129) or oral semaglutide (n=46) in clinical practice. Weight, BMI, and HbA1c were measured at baseline, 6, 12, and 24 months (24-month data available for injectable group only).

Why This Research Matters

Real-world data fills a critical gap between clinical trial efficacy and actual clinical practice. Patients in trials are carefully selected and monitored, while real-world patients have comorbidities, variable adherence, and diverse lifestyles. This study confirms that semaglutide's weight loss and glycemic benefits persist in everyday practice, and that weight continues to improve through 24 months — addressing the common patient concern of 'will it keep working?'

The Bigger Picture

This study contributes to the growing body of real-world evidence showing that semaglutide's clinical trial results translate to practice. The comparison between injectable and oral forms is particularly valuable as more patients and clinicians consider the convenience of oral semaglutide. The finding that injectable semaglutide produced progressive weight loss through 24 months (not a plateau at 6-12 months) suggests that the metabolic benefits compound over time with continued use.

What This Study Doesn't Tell Us

This is a retrospective study without randomization between injectable and oral groups — the groups differed in age, sex distribution, and baseline characteristics. There's no placebo comparison. The 24-month data is only available for injectable semaglutide, preventing long-term comparison with the oral form. Dropout and adherence data are not clearly reported. Specific semaglutide doses are not detailed. The single-center Italian population may not be representative of all patient groups.

Questions This Raises

  • ?Will oral semaglutide maintain comparable effectiveness to injectable through 24 months and beyond?
  • ?What happens to weight when semaglutide is discontinued in real-world practice — do patients regain?
  • ?Are there patient characteristics that predict better response to injectable versus oral semaglutide?

Trust & Context

Key Stat:
-15.9 kg at 24 months with injectable semaglutide Weight loss didn't plateau — injectable semaglutide users continued losing weight from 10.4 kg at 6 months to 15.9 kg at 24 months in real-world practice, demonstrating sustained and progressive benefit with continued treatment.
Evidence Grade:
This is a Level II retrospective observational study without randomization or placebo control. While it provides valuable real-world effectiveness data, the lack of randomization between injectable and oral groups and the absence of a control arm limit causal conclusions. The consistent results across multiple timepoints strengthen confidence in the findings.
Study Age:
Published in 2025, this study provides up-to-date real-world evidence reflecting current semaglutide prescribing practices and formulations available.
Original Title:
Real-world effectiveness of Semaglutide treatment on weight loss maintenance after weight loss in patients with obesity or overweight and diabetes.
Published In:
Eating and weight disorders : EWD, 30(1), 2 (2025)
Database ID:
RPEP-10680

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study
What do these levels mean? →

Frequently Asked Questions

Does semaglutide keep working long-term or does it stop after a few months?

This real-world study provides reassuring evidence: injectable semaglutide users kept losing weight from 6 months (10.4 kg) through 24 months (15.9 kg). There was no plateau or weight regain during continued treatment. Oral semaglutide showed a similar pattern, with weight loss increasing from 6.7 kg at 6 months to 10.7 kg at 12 months. The key is continued use — the benefits depend on staying on the medication.

Is the oral pill as effective as the injection?

In this study, oral semaglutide produced slower initial weight loss (6.7 kg vs 10.4 kg at 6 months) but caught up substantially by 12 months (10.7 kg oral vs 9.3 kg injectable). The authors conclude the two forms have comparable effectiveness, though injectable semaglutide may work faster initially. For patients who prefer not to inject, the oral pill appears to be a viable alternative that achieves similar long-term results.

Read More on RethinkPeptides

Related articles coming soon.

Cite This Study

RPEP-10680·https://rethinkpeptides.com/research/RPEP-10680

APA

Del Prete, Michela; Gavazzi, Lidia; Disoteo, Olga Eugenia; Vignati, Federico; Di Sacco, Gianleone; Muratori, Fabrizio. (2025). Real-world effectiveness of Semaglutide treatment on weight loss maintenance after weight loss in patients with obesity or overweight and diabetes.. Eating and weight disorders : EWD, 30(1), 2. https://doi.org/10.1007/s40519-024-01711-2

MLA

Del Prete, Michela, et al. "Real-world effectiveness of Semaglutide treatment on weight loss maintenance after weight loss in patients with obesity or overweight and diabetes.." Eating and weight disorders : EWD, 2025. https://doi.org/10.1007/s40519-024-01711-2

RethinkPeptides

RethinkPeptides Research Database. "Real-world effectiveness of Semaglutide treatment on weight ..." RPEP-10680. Retrieved from https://rethinkpeptides.com/research/del-2025-realworld-effectiveness-of-semaglutide

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.