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Review of new-user target trial emulation comparing semaglutide and SGLT2i in U.S. Veterans with type 2 diabetesSemaglutide Does Not Raise Suicide Risk, Study Finds

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Key Takeaway
Note no increased risk of suicidality with semaglutide vs SGLT2i in this observational emulation.

This publication is a review and synthesis of an active-comparator, new-user target trial emulation conducted within the Veterans Health Administration. The study population comprised 102,361 Veterans with type 2 diabetes, including 11,478 new initiators of semaglutide and 90,883 new initiators of SGLT2i. The median follow-up duration was 2.2 years. The primary outcomes assessed were incident suicidal ideation, suicide attempt or death, and a composite outcome.

Regarding incident suicidal ideation, the incidence rate was 56.3 per 1000 person-years for semaglutide versus 37.7 per 1000 person-years for SGLT2i. The hazard ratio was 0.99 with a 95% CI of 0.93-1.06 (P = 0.86), indicating no increased risk. For suicide attempts or deaths, rates were 4.30 per 1000 person-years (semaglutide) versus 2.64 per 1000 person-years (SGLT2i). The hazard ratio was 1.05 (95% CI, 0.84-1.31; P = .86), also showing no increased risk.

In adherence-adjusted analyses, sustained semaglutide treatment for more than 12 months versus 6 or fewer months was associated with a hazard ratio of 0.27 (95% CI, 0.14-0.54; P<.001), representing a 74% lower risk. Absolute numbers for suicide attempts or deaths were 696. The authors note that adverse events, serious adverse events, and discontinuations were not reported. Because this is an observational emulation, causal inferences are limited, and findings should be interpreted with caution regarding practice relevance.

  • No rise in suicidal thoughts with semaglutide vs. other diabetes drugs
  • Helps millions with type 2 diabetes and obesity concerns
  • Long-term use may lower suicide risk — but not yet proven for all

This could ease fears stopping patients from life-changing treatment.

You’re managing your type 2 diabetes. You’ve tried diet, exercise, pills. Your doctor suggests a newer injectable drug — one that helps control blood sugar and can lead to major weight loss. But you’ve heard whispers online: Could it make you suicidal? That fear stops many from starting a treatment that could change their health.

Now, a large new study offers strong reassurance.

Millions of people take semaglutide. You may know it as Ozempic or Wegovy. It’s used for type 2 diabetes and weight management. And it works — often remarkably well.

But rumors have swirled for years. Some social media posts claim it triggers depression or suicidal thoughts. A few case reports added fuel. Doctors started to wonder: Should we be worried?

For patients, this creates real stress. They want better health — but not at the cost of their mental well-being.

The surprising shift

For years, any new drug with a possible mental health side effect raises red flags. That’s smart medicine. But it can also create fear before facts are clear.

Many assumed semaglutide might increase suicide risk. After all, it acts in the brain — helping control hunger. Could it also affect mood?

But here’s the twist: this study found no sign of increased risk. In fact, the opposite may be true over time.

What scientists didn’t expect

The study looked at over 100,000 U.S. veterans with type 2 diabetes. Half started semaglutide. The other half started a different diabetes drug — an SGLT2 inhibitor, like Farxiga or Jardiance.

These two drug classes work differently. But both help lower blood sugar and protect the heart. They’re often compared in real-world care.

Researchers tracked who developed suicidal thoughts or attempts after starting treatment.

Think of your brain like a control center. It gets signals from your body about hunger, stress, and mood.

Semaglutide mimics a hormone called GLP-1. It’s like a key that fits into locks in your brain and gut. One lock turns down appetite. Another may influence mood and stress responses.

Some worried this brain activity could backfire. But the new data suggest it doesn’t — and might even help over time.

A closer look at the results

The study followed patients for over two years on average. It compared suicide-related events between the two groups.

For suicidal thoughts: 56 people per 1,000 years on semaglutide had an event. That’s slightly higher than the 38 per 1,000 on the other drug. But statistically? No real difference.

For suicide attempts or death: rates were 4.3 vs. 2.6 per 1,000. Again, not a significant rise.

This doesn’t mean this treatment is available yet.

But there’s a catch.

When researchers looked at how long people stayed on semaglutide, something unexpected emerged.

Patients who used it for more than 12 months had a 74% lower risk of suicide attempt or death compared to those on it for 6 months or less.

That’s a big drop. And it stayed true even after adjusting for how closely people followed their treatment.

Why longer use might help

Could semaglutide be protecting mental health over time?

We can’t say for sure. But think about this: losing weight, gaining energy, seeing lab numbers improve — these changes boost confidence and mood.

Also, better blood sugar control may reduce brain fog and irritability. Chronic illness takes a mental toll. When symptoms ease, mental health often follows.

It’s not that the drug is an antidepressant. But helping the body may help the mind, too.

What patients need to know

If you’re considering semaglutide, this study should offer peace of mind. Starting the drug did not increase suicide risk compared to another common diabetes medication.

And if you stay on it long-term? You might even see added mental health benefits — though more research is needed to confirm why.

Talk to your doctor if you have a history of depression or mental health concerns. They can help weigh risks and benefits for you.

The full picture

Experts say this study is one of the strongest to date on this question. It used real-world data from a large, diverse group. It compared similar patients. And it tracked outcomes carefully.

Still, the group studied was mostly older male veterans — a population already at higher risk for suicide. That makes the findings even more reassuring.

If no rise in risk showed up here, it’s unlikely to appear in lower-risk groups.

Not all hope is equal

The drop in suicide attempts among long-term users is promising. But we can’t say semaglutide caused it. Maybe healthier patients simply stayed on the drug longer.

That’s a common challenge in medical research. It’s hard to tell if the drug causes the benefit — or if those already doing better are more likely to keep taking it.

Still, the result should prompt deeper study, not fear.

This study adds strong evidence that semaglutide does not increase suicide risk. That message needs to reach patients and doctors.

Future research should check if these results hold in younger, more diverse groups — including women and non-veterans.

For now, fear of mental harm should not block access to a medicine that helps so many.

Study Details

EvidenceLevel 5
PublishedApr 2026
View Original Abstract ↓
Importance: Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), is a highly effective medication to treat type 2 diabetes and obesity. However, concerns about potential suicidality persist, creating clinical uncertainty about its neuropsychiatric safety. Objective: To assess risks of suicidality after initiating semaglutide compared to initiating SGLT2i and by duration of continuous semaglutide treatment. Design: Active-comparator, new-user target trial emulation to estimate inverse probability-weighted marginal cause-specific hazard ratios (HRs). For duration-of-treatment analyses, we used clone-censor-weight methods to estimate exposure-adjusted effects. Setting: Veterans Health Administration. Participants: U.S. Veterans with type 2 diabetes receiving care from March 1, 2018 to September 1, 2025. Exposure: Initiation of semaglutide vs SGLT2i; duration of semaglutide use (<=6, 7-12, >12 months). Outcomes: Incident suicidal ideation; suicide attempt or death; and a composite outcome. Results: A total of 102,361 Veterans met inclusion criteria, including 11,478 new initiators of semaglutide and 90,883 new initiators of an SGLT2i. After overlap weighting, baseline characteristics were well balanced between treatment groups (mean [SD] age, 60.1 [11.7] years; BMI, 37.8 [6.8] kg/m2; hemoglobin A1c, 7.0% [1.4]; 85.5% male; 61.9% non-Hispanic White). During a median follow-up of 2.2 years, 9077 incident suicidal ideation events and 696 suicide attempts or deaths occurred. The incidence rate of suicidal ideation was 56.3 and 37.7 per 1000 person-years among semaglutide initiators and SGLT2i initiators, respectively (hazard ratio [HR], 0.99; 95% CI, 0.93-1.06; P = 0.86). For suicide attempts or deaths, the incidence rates were 4.30 and 2.64 per 1000 person-years, respectively (HR, 1.05; 95% CI, 0.84-1.31; P = .86). In adherence-adjusted analyses, sustained semaglutide treatment for more than 12 months, compared with 6 or fewer months, was associated with a 74% lower risk of suicide attempts or deaths (HR, 0.27; 95% CI, 0.14-0.54; P<.001). Conclusion: Among U.S. Veterans with type 2 diabetes, initiators of semaglutide were not observed to have an increased risk of suicidality compared with initiators of SGLT2i. Those with longer semaglutide treatment (beyond 12 months) had decreased risk of suicide attempt or death, suggesting longer term treatment is safe and may protect against for those outcomes.
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