There's a lot of noise about GLP-1 medications—claims and counterclaims, fears and hype. What does the actual research show? Here's a plain-English breakdown of what we know, what we don't, and how confident we should be.
Weight Loss Efficacy
What the Studies Show
Large clinical trials consistently demonstrate significant weight loss. The STEP trials (for semaglutide/Wegovy) showed average weight loss of 15-17% of body weight over 68 weeks. The SURMOUNT trials (for tirzepatide/Zepbound) showed even higher—up to 20-22% average weight loss.
These aren't cherry-picked results—they're averages from trials with thousands of participants, including people who dropped out or didn't respond well.
Cardiovascular Benefits
What the Studies Show
The SELECT trial (over 17,000 participants followed for years) found that semaglutide reduced major cardiovascular events—heart attack, stroke, cardiovascular death—by 20% compared to placebo in people with existing cardiovascular disease but without diabetes.
This is independent of weight loss and suggests the medication has direct cardiovascular benefits. The FDA has approved Wegovy specifically for cardiovascular risk reduction.
Blood Sugar Control
What the Studies Show
GLP-1 medications were originally developed for diabetes and have extensive evidence for improving blood sugar control. They reduce HbA1c (a measure of long-term blood sugar) significantly—typically by 1-2 percentage points. Many people with type 2 diabetes reduce or eliminate other medications.
Weight Regain After Stopping
What the Studies Show
The STEP 4 trial showed that people who stopped semaglutide regained about two-thirds of lost weight within a year. Other studies show similar patterns. This suggests the medications treat but don't cure obesity—similar to how blood pressure medications treat but don't cure hypertension.
This is why many experts recommend viewing GLP-1 medications as long-term or indefinite treatment, not a temporary intervention.
Common Side Effects
What the Studies Show
GI side effects (nausea, vomiting, diarrhea, constipation) are common, especially early in treatment and during dose increases. In trials, 40-70% experienced some GI symptoms. However, these are typically mild-to-moderate and improve over time. Discontinuation due to side effects runs around 5-10% in trials.
Serious Risks: What's Real vs. Overblown
Pancreatitis
What the Studies Show
There's a small increased risk of pancreatitis—inflammation of the pancreas. In large trials, this occurred in less than 1% of participants. It's a real risk but rare. People with history of pancreatitis should avoid these medications.
Thyroid Cancer
What the Studies Show
In rodent studies, GLP-1 medications caused thyroid C-cell tumors. However, this hasn't been observed in humans despite years of use. The medication carries a warning about medullary thyroid carcinoma and is contraindicated in people with personal or family history of MTC or MEN2 syndrome.
Gallbladder Issues
What the Studies Show
Rapid weight loss (from any method) increases gallstone risk. GLP-1 trials show modestly elevated rates of gallbladder-related events. This is likely related to the weight loss itself rather than the medication directly.
Gastroparesis / Stomach Paralysis
What the Studies Show
GLP-1 medications slow gastric emptying—that's part of how they work. In most people this causes temporary nausea. Severe gastroparesis appears to be rare in clinical trials but has been reported. People with existing gastroparesis should use caution.
What We Don't Know Yet
Honest gaps in evidence:
- Very long-term safety (10+ years): The medications haven't been used at scale for that long yet. We're still accumulating data.
- Effects during pregnancy: Not well studied; currently not recommended during pregnancy.
- Effects in people under 18: Limited data; some approvals emerging for adolescents.
- Ideal duration of treatment: Lifelong? Intermittent? We don't have definitive answers.
- Best strategies for weight maintenance after stopping: Still being studied.
Mental Health Effects
What the Studies Show
Some concern emerged about suicidal ideation, prompting FDA review. So far, analyses of clinical trial data have not found increased risk compared to placebo. The FDA continues monitoring. Meanwhile, many users report improved mental health as weight decreases and food obsession diminishes.
The Bottom Line
GLP-1 medications have strong evidence for:
- Significant weight loss
- Cardiovascular benefit
- Blood sugar improvement
- Manageable (if common) side effects
Legitimate cautions include:
- Weight regain if stopped
- Small risk of pancreatitis
- Potential gallbladder issues with rapid loss
- Unknown very long-term effects
The evidence doesn't support:
- Claims these are "dangerous drugs"
- Claims these are "easy fixes" (they require lifestyle changes too)
- Either extreme—uncritical enthusiasm or fear-based rejection
Like any medical treatment, GLP-1 medications involve tradeoffs. The evidence suggests the benefits significantly outweigh risks for most people with obesity—but informed decision-making requires understanding both.