Keywords: Type 1 diabetes, obesity, semaglutide, GLP-1 receptor agonist, weight loss, glycemic control, insulin therapy
Managing both type 1 diabetes (T1D) and obesity remains a significant clinical challenge. While intensive insulin therapy is lifesaving for individuals with T1D, it often contributes to weight gain, further complicating metabolic control and increasing the risk of long-term complications such as cardiovascular disease, nephropathy, and neuropathy. In this context, a recently published double-blind randomized trial in NEJM Evidence offers important preliminary data supporting the use of semaglutide—a GLP-1 receptor agonist—as an adjunct treatment for adults with T1D and obesity.
This study is among the first clinical trials to evaluate semaglutide specifically in adults with T1D using automated insulin delivery (AID) systems, shedding light on a potential new approach to dual glycemic and weight management in this population.
Background: The Dual Burden of T1D and Obesity
T1D is an autoimmune disease in which the destruction of pancreatic beta cells leads to absolute insulin deficiency. Insulin therapy is mandatory for survival but is also associated with anabolic effects that promote fat storage. Many patients struggle with excess weight gain, leading to a paradox where the treatment for one condition exacerbates another.
Obesity in T1D is more than a cosmetic concern. It contributes to insulin resistance, increases the cardiometabolic risk, and limits the effectiveness of current diabetes technologies. Unfortunately, there are limited approved pharmacologic options for weight management in T1D, and GLP-1 receptor agonists have not been widely studied in this population until recently.
The Study: Semaglutide in T1D With Obesity
The randomized, placebo-controlled, double-blind trial included 72 adults with T1D, all of whom had a BMI ≥30 kg/m² and were using automated insulin delivery systems. Over a period of 26 weeks, participants were assigned to receive either once-weekly semaglutide or placebo, in addition to their ongoing insulin therapy.
Primary Clinical Goals:
Researchers measured success using three combined outcomes:
- Time in range (TIR): >70% of glucose readings between 70–180 mg/dL
- Time in hypoglycemia: <4% below 70 mg/dL
- Weight reduction: ≥5% of baseline body weight
Key Findings
- 36% of patients in the semaglutide group achieved all three health goals, compared to 0% in the placebo group.
- Participants in the treatment arm lost an average of 18.5–20 pounds over six months.
- These improvements occurred without an increased risk of severe hypoglycemia or diabetic ketoacidosis (DKA).
| Achieved all three health goals* (%) | 36% | 0% |
| Average weight loss over 6 months (lbs) | 18.5 – 20 | Not significant |
Importantly, these benefits were observed despite the absence of endogenous insulin production, suggesting that the effects of semaglutide on gastric emptying, appetite suppression, and possibly insulin sensitivity may play key roles in its efficacy in T1D.
Mechanisms of Action and Clinical Relevance
Although GLP-1 receptor agonists are not expected to stimulate endogenous insulin in T1D, semaglutide may offer several indirect metabolic advantages:
- Delayed gastric emptying reduces postprandial glucose spikes.
- Central appetite suppression aids in weight loss and reduces caloric intake.
- Improved insulin sensitivity may allow for lower exogenous insulin requirements, reducing the risk of weight gain and glycemic variability.
For patients with T1D who are already using insulin pumps or AID systems, the addition of semaglutide may allow for more stable glucose profiles while also addressing obesity—a comorbidity that has long lacked effective treatment options in this group.
Safety Profile
The semaglutide group did not show a higher incidence of severe hypoglycemia or DKA—two of the most feared complications in insulin-treated patients. Gastrointestinal side effects were present but manageable, consistent with known effects of GLP-1 receptor agonists.
These results are encouraging and suggest that semaglutide can be safely added to advanced insulin therapies in a controlled setting.
Clinical Implications and Future Directions
Although semaglutide is currently approved only for T2DM and obesity, this study paves the way for potential off-label and investigational use in T1D with comorbid obesity.
If future larger trials confirm these findings, clinicians may soon have a powerful adjunctive therapy to address two pressing concerns in T1D:
- Glycemic variability
- Progressive weight gain
This may be particularly relevant in adult patients with T1D who are already using advanced insulin technologies, such as hybrid closed-loop systems, and who continue to struggle with metabolic control due to excess weight.
Conclusion
This study offers promising preliminary evidence that semaglutide, when added to insulin therapy in adults with type 1 diabetes and obesity, may support significant weight loss, better glycemic control, and reduced insulin burden, all without compromising safety.
While regulatory approval is still pending for use in T1D, the findings represent a hopeful step forward for a population with few effective tools to manage obesity. Future large-scale studies are warranted to confirm efficacy, optimize dosing, and explore long-term outcomes.
As the clinical landscape continues to evolve, semaglutide may one day become an important adjunct in the personalized care of individuals living with both type 1 diabetes and obesity—two chronic conditions that have historically been difficult to manage in tandem.