Most Important GLP-1 Studies (2023–2026): Evidence Behind Ozempic, Wegovy and New Weight-Loss Drugs

- September 07, 2026

Introduction

In recent years, GLP-1 receptor agonists have emerged as one of the most important breakthroughs in modern metabolic medicine. Originally developed to treat type 2 diabetes, these medications are now widely used for weight loss, cardiovascular risk reduction, and metabolic disease management. Drugs such as Ozempic, Wegovy, and Mounjaro have rapidly gained global attention for their ability to produce significant and sustained weight loss while improving multiple cardiometabolic risk factors.

GLP-1 (glucagon-like peptide-1) is a natural hormone released from the gut after eating. It plays a key role in regulating blood sugar, appetite, and digestion. By mimicking or enhancing this hormone’s activity, GLP-1 drugs help reduce hunger, slow gastric emptying, improve insulin secretion, and support healthier glucose control. Over the past decade, large randomized clinical trials have demonstrated that these medications can lead to 10–20% reductions in body weight, alongside meaningful improvements in blood pressure, cholesterol levels, and inflammatory markers.

Beyond weight management, emerging research shows that GLP-1 therapies may also provide cardiovascular and kidney protection. Major clinical trials have reported reductions in heart attacks, strokes, and cardiovascular mortality among high-risk patients using GLP-1–based therapies. These findings have shifted the perception of GLP-1 drugs from simple diabetes medications to broad cardiometabolic therapies with potential applications across obesity, heart disease, and metabolic syndrome.

At the same time, the rapid expansion of GLP-1 drug use has raised new scientific questions. Researchers are continuing to investigate long-term safety, optimal treatment duration, and possible effects on areas such as bone health, muscle mass, and gastrointestinal function. Meanwhile, next-generation drugs that combine GLP-1 activity with additional metabolic pathways are already being developed, potentially offering even greater therapeutic benefits.

Update: Retatrutide 2026: Phase 3 results, FDA timeline, vs. Wegovy/Zepbound.

This article provides an updated compilation of the most important GLP-1 studies from 2023 to 2026, summarizing the latest clinical trials, meta-analyses, and emerging research on these widely discussed medications. By reviewing the evidence behind GLP-1 therapies, readers can better understand their benefits, limitations, and future role in metabolic and cardiovascular medicine.

1. Cardiovascular Outcome Trials (Major Landmark Evidence)

SELECT Trial (2023–2024)

Population: 17,604 adults with obesity or overweight without diabetes
Drug: Semaglutide 2.4 mg weekly
Results:
- 20% reduction in major adverse cardiovascular events (MACE)
- Reduced risk of heart attack, stroke, and cardiovascular death
Impact: Expanded GLP-1 use beyond diabetes to cardiovascular risk reduction in obesity. (MDPI 2025)

The SELECT Trial: Semaglutide and Cardiovascular Risk Without Diabetes

SELECT (Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity) is the trial that moved semaglutide from a weight-loss drug into a cardiovascular-protection drug. Published in the New England Journal of Medicine in November 2023 (Lincoff et al.), it enrolled 17,604 adults across 804 sites in 41 countries — all at least 45 years old, with a BMI of 27 or higher, established cardiovascular disease, and no diagnosis of diabetes. Participants were randomized 1:1 to once-weekly subcutaneous semaglutide 2.4 mg or placebo, both added to standard of care, and followed for a mean of 39.8 months.

What SELECT found

Primary outcome (3-point MACE — cardiovascular death, nonfatal MI, or nonfatal stroke): 6.5% with semaglutide vs 8.0% with placebo — a hazard ratio of 0.80 (95% CI, 0.72–0.90), a 20% relative risk reduction.
Incident type 2 diabetes: reduced by roughly 73% in participants with prediabetes at baseline, a striking secondary finding given that two-thirds of the trial population had dysglycemia going in.
Weight loss: a mean reduction of 10.2% of body weight at 208 weeks (4 years) versus 1.5% with placebo — and, notably, subgroup analyses found the cardiovascular benefit held across baseline weight and waist-circumference categories, suggesting the heart protection isn't purely a function of how much weight was lost.
Kidney outcomes (prespecified secondary analysis): a composite kidney endpoint — kidney disease death, dialysis initiation, sustained eGFR under 15, or a sustained ≥50% eGFR decline — occurred in 1.8% of the semaglutide group versus 2.2% of placebo (HR 0.78, 95% CI 0.63–0.96, P = 0.02), roughly a 22% relative risk reduction. This finding foreshadowed the dedicated FLOW trial discussed later in this guide.
Heart failure subgroup: in participants who had heart failure at baseline (about a fifth of the trial), semaglutide reduced both MACE (HR 0.72) and a composite heart-failure outcome (HR 0.79), with consistent benefit regardless of heart failure subtype.

Clinically, SELECT is what led the FDA to approve Wegovy (semaglutide 2.4 mg) in March 2024 for reducing the risk of cardiovascular death, heart attack, and stroke in adults with established cardiovascular disease and either obesity or overweight — independent of a diabetes diagnosis. It was also the first GLP-1 cardiovascular outcomes trial conducted specifically in a non-diabetic population, which matters because earlier CV benefit data for this drug class (SUSTAIN-6, LEADER, REWIND) came from people who already had diabetes.

REWIND Trial

Drug: Dulaglutide
Population: Type 2 diabetes with cardiovascular risk
Results:
- 12% reduction in cardiovascular events
Significance: Demonstrated cardioprotection even in lower-risk diabetes populations. (MDPI 2025)

Meta-analysis of 13 Cardiovascular Trials

Sample: 83,258 patients
Findings:
- Reduced
  - all-cause mortality
  - cardiovascular mortality
  - stroke
  - coronary revascularization
  - major cardiovascular events (MACE) (MDPI)

2. Diabetes and Metabolic Outcomes

GLP-1 vs DPP-4 Cohort Study (JAMA Network Open 2025)

Findings

Lower cardiovascular risk in type 2 diabetes patients
Strong kidney protection across BMI categories
Mechanisms:
- improved insulin sensitivity
- reduced inflammation
- reduced hepatic fat
- improved adipokine profile (Ovid)

GLP-1 in Peripheral Artery Disease (2025 Meta-analysis)

Participants: 7,645 patients
Results
- 17% reduction in all-cause mortality
- 14% reduction in MACE
- improved HbA1c levels
No clear benefit yet for limb-specific outcomes. (PubMed)

3. Weight Loss Trials

STEP Trials (Semaglutide)

Typical outcomes:

STEP-1 (obesity without diabetes): ~15% body weight loss
STEP-2 (obesity + diabetes): ~9–10% weight loss
STEP-4 (maintenance trial): sustained weight reduction

These trials established semaglutide as one of the most effective anti-obesity drugs ever developed.

Lifestyle + GLP-1 Meta-analysis (2025)

33 randomized trials (12,028 participants)

Results:

Weight loss: −7.13 kg
Waist circumference: −5.7 cm
HbA1c reduction
lower triglycerides
lower LDL cholesterol
lower blood pressure (PubMed)

4. Cardiometabolic Effects

Meta-analysis of GLP-1 receptor agonists showed:

reduced systolic blood pressure (~5 mmHg)
reduced myocardial infarction risk (28%)
improved metabolic markers in obesity populations. (PubMed)

Mechanisms include:

appetite suppression
delayed gastric emptying
improved insulin sensitivity
anti-inflammatory effects
endothelial protection

Emerging New Research (2025–2026)

Potential Cardiovascular Applications

Recent experimental research suggests GLP-1 drugs may:

improve microvascular blood flow after heart attacks
reduce complications such as “no-reflow syndrome” following cardiac interventions. (The Guardian)

New Adverse Effects Being Investigated

Skeletal Effects

Large observational analysis (~150,000 patients):

Possible increased risk of:

osteoporosis (+30%)
osteomalacia (+150%)
tendon rupture (+50%) (The Washington Post)

Mechanisms proposed:

rapid weight loss
reduced mechanical bone loading
nutritional deficiencies.

Hair Loss

Reported in some patients using GLP-1 drugs, but likely related to:

rapid weight loss
protein or micronutrient deficiency. (Allure)

Emerging Next-Generation GLP-1 Drugs

Current development trends include:

Dual and Triple Agonists

Examples:

GLP-1/GIP agonists
GLP-1/glucagon agonists

Goals:

greater weight loss
improved metabolic control
less gastrointestinal side effects

These drugs could become the next generation of metabolic therapeutics.

Oral GLP-1 Weight-Loss Pills

GLP-1 receptor agonists have transformed obesity treatment, but the best-known medicines were initially injectable. Oral formulations are now creating a new competitive segment aimed at people who prefer a tablet to an injection.

Two major oral obesity medicines are now competing in the United States: Wegovy pill (oral semaglutide) from Novo Nordisk and Foundayo (orforglipron) from Eli Lilly.

Wegovy pill became broadly available in the United States on January 5, 2026. Foundayo was approved by the FDA on April 1, 2026 and became commercially available in April 2026.

Read more: Wegovy Pill vs Foundayo Pill: Comparison, Price and Side Effects (2026)

Key Clinical Takeaways

1. GLP-1 drugs are now cardiometabolic drugs, not just diabetes drugs.

Evidence shows reductions in:

cardiovascular death
stroke
heart attack
kidney disease

2. Weight loss effect is among the strongest of any medication

Typical outcomes:

10–15% body weight loss

3. Benefits extend beyond glucose control

They improve:

inflammation
endothelial function
blood pressure
lipid profile

4. Long-term safety monitoring is still ongoing

Potential concerns:

bone density
gallbladder disease
pancreatitis
nutritional deficiencies.

Related: SELECT, STEP, SURPASS & FLOW GLP 1 Clinical Trials: What the Landmark Semaglutide and Tirzepatide Trials Actually Prove (2026)