Branded GLP-1 Drugs: Complete Market Comparison 2026
A decade ago, GLP-1 receptor agonists were a niche class of diabetes drugs most people had never heard of. Today, they are the fastest-growing drug class in pharmaceutical history. The global GLP-1 receptor agonist market was valued at $70.08 billion in 2025 and is projected to reach $201.
A decade ago, GLP-1 receptor agonists were a niche class of diabetes drugs most people had never heard of. Today, they are the fastest-growing drug class in pharmaceutical history. The global GLP-1 receptor agonist market was valued at $70.08 billion in 2025 and is projected to reach $201.79 billion by 2033. Semaglutide alone — sold as Ozempic, Wegovy, and Rybelsus — held 37.77% of the market in 2025.
But semaglutide is no longer the only game worth watching. Tirzepatide (Mounjaro, Zepbound) has shown superior weight loss in head-to-head trials. An oral pill from Eli Lilly called orforglipron could receive FDA approval in 2026, removing the need for injections entirely. Retatrutide, a triple agonist, just delivered 28.7% weight loss in its first Phase 3 trial — the highest ever seen in a late-stage obesity trial. And Novo Nordisk's CagriSema produced 22.7% weight loss by combining semaglutide with an amylin analog.
This guide compares every GLP-1 medication on the market and the most important drugs in the pipeline — their mechanisms, efficacy data, side effects, dosing, pricing, and FDA-approved indications.
Table of Contents
- How GLP-1 Drugs Work
- Currently FDA-Approved GLP-1 Medications
- Semaglutide (Ozempic, Wegovy, Rybelsus)
- Tirzepatide (Mounjaro, Zepbound)
- Liraglutide (Victoza, Saxenda)
- Dulaglutide (Trulicity)
- Exenatide (Byetta, Bydureon)
- Lixisenatide (Adlyxin, Soliqua)
- Head-to-Head Efficacy Comparison
- Pipeline Drugs to Watch in 2026-2027
- Orforglipron — The First Non-Peptide Oral GLP-1
- Retatrutide — The Triple Agonist
- CagriSema — Semaglutide Plus Amylin
- Survodutide — Glucagon/GLP-1 Dual Agonist
- MariTide — Monthly GLP-1/GIP Bispecific
- Pricing and Access in 2026
- Expanding Indications Beyond Diabetes and Obesity
- Side Effects Across the Class
- Complete Comparison Table
- The Bottom Line
- References
How GLP-1 Drugs Work
GLP-1 (glucagon-like peptide-1) is a hormone your gut releases after you eat. It signals the pancreas to produce insulin, tells the liver to slow glucose production, slows stomach emptying, and sends satiety signals to the brain. The result: lower blood sugar and reduced appetite.
Natural GLP-1 has a half-life of about two minutes — your body breaks it down almost immediately. GLP-1 drugs are engineered versions that resist this breakdown, extending their activity from minutes to hours or days.
The newer drugs go beyond GLP-1 alone:
- Single agonists (semaglutide, liraglutide) — Target the GLP-1 receptor only
- Dual agonists (tirzepatide) — Target GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptors
- Dual agonists (survodutide) — Target GLP-1 and glucagon receptors
- Triple agonists (retatrutide) — Target GLP-1, GIP, and glucagon receptors simultaneously
- Combination therapies (CagriSema) — Pair GLP-1 agonism with amylin analog activity
Each additional receptor target generally translates to greater weight loss and metabolic benefits, though also potentially more side effects.
Currently FDA-Approved GLP-1 Medications
There are currently 11 FDA-approved GLP-1 medications across six active ingredients. Here is a detailed look at each.
Semaglutide (Ozempic, Wegovy, Rybelsus)
Manufacturer: Novo Nordisk Mechanism: GLP-1 receptor agonist First approved: 2017 (Ozempic), 2021 (Wegovy), 2019 (Rybelsus)
Semaglutide is the best-known and best-studied GLP-1 drug. It is the only GLP-1 agonist available in both injectable and oral formulations.
Formulations and Dosing
| Brand | Route | Frequency | Indication | Dose Range |
|---|---|---|---|---|
| Ozempic | SC injection | Once weekly | Type 2 diabetes | 0.25-2 mg |
| Wegovy | SC injection | Once weekly | Obesity/overweight | 0.25-2.4 mg |
| Wegovy Pill | Oral tablet | Once daily | Obesity/overweight | Up to 50 mg |
| Rybelsus | Oral tablet | Once daily | Type 2 diabetes | 3-14 mg |
The oral Wegovy pill was FDA-approved in December 2025 and launched in January 2026 — the first GLP-1 pill approved for obesity. The starting dose is available for $149 per month through select providers.
Key Efficacy Data
- Weight loss (injectable 2.4 mg): 13.9% at 68 weeks in the STEP 1 trial
- Weight loss (oral 50 mg): 12.7% at 68 weeks
- HbA1c reduction: Up to 1.8% with injectable formulation
- Cardiovascular benefit: 20% reduction in major adverse cardiovascular events (SELECT trial)
Approved Indications (as of early 2026)
- Type 2 diabetes (Ozempic, Rybelsus)
- Chronic weight management (Wegovy injectable and oral)
- Cardiovascular risk reduction in Type 2 diabetes (Rybelsus — approved October 2025)
- Chronic kidney disease risk reduction in Type 2 diabetes (Ozempic — approved January 2025)
For a deeper dive, see our complete semaglutide pharmacology guide.
Tirzepatide (Mounjaro, Zepbound)
Manufacturer: Eli Lilly Mechanism: Dual GIP/GLP-1 receptor agonist First approved: 2022 (Mounjaro), 2023 (Zepbound)
Tirzepatide is the first dual GIP/GLP-1 agonist to reach the market. By activating both the GLP-1 and GIP receptors, it produces greater insulin secretion, stronger appetite suppression, and more weight loss than GLP-1-only drugs.
Formulations and Dosing
| Brand | Route | Frequency | Indication | Dose Range |
|---|---|---|---|---|
| Mounjaro | SC injection | Once weekly | Type 2 diabetes | 2.5-15 mg |
| Zepbound | SC injection | Once weekly | Obesity/overweight | 2.5-15 mg |
Key Efficacy Data
The landmark SURMOUNT-5 trial directly compared tirzepatide to semaglutide in people with obesity (no diabetes):
| Outcome | Tirzepatide (15 mg) | Semaglutide (2.4 mg) |
|---|---|---|
| Weight loss at 72 weeks | -20.2% | -13.7% |
| Waist circumference reduction | -18.4 cm | -13.0 cm |
| Cost per 1% weight reduction | $985 | $1,845 |
Tirzepatide was statistically superior to semaglutide on both primary endpoints (P <.001).
For Type 2 diabetes, the SURPASS-2 trial found tirzepatide at all doses was noninferior and superior to semaglutide 1 mg for HbA1c reduction.
Additional Approved Indication
In late 2024, Zepbound became the first GLP-1 drug (and first medication of any kind) approved by the FDA for obstructive sleep apnea — marking the class's expansion beyond metabolic disease.
Liraglutide (Victoza, Saxenda)
Manufacturer: Novo Nordisk Mechanism: GLP-1 receptor agonist First approved: 2010 (Victoza), 2014 (Saxenda)
Liraglutide was the second GLP-1 agonist approved by the FDA and the first to receive an obesity indication. While it has been largely eclipsed by semaglutide and tirzepatide for weight loss, it remains widely prescribed for diabetes.
Formulations and Dosing
| Brand | Route | Frequency | Indication | Dose Range |
|---|---|---|---|---|
| Victoza | SC injection | Once daily | Type 2 diabetes | 0.6-1.8 mg |
| Saxenda | SC injection | Once daily | Obesity/overweight | 0.6-3.0 mg |
Key Efficacy Data
- Weight loss (3.0 mg, Saxenda): ~8% at 56 weeks
- HbA1c reduction: ~1.1-1.5%
- Cardiovascular benefit: 13% reduction in MACE (LEADER trial)
Generic Availability
In August 2025, the FDA approved the first generic version of liraglutide (Saxenda) for weight loss. This may make liraglutide a cost-effective option for patients who cannot afford newer GLP-1 drugs, even though its efficacy is lower.
Pediatric Use
Saxenda is approved for chronic weight management in patients aged 12 and older with obesity — one of the few GLP-1 drugs approved for adolescents.
Dulaglutide (Trulicity)
Manufacturer: Eli Lilly Mechanism: GLP-1 receptor agonist First approved: 2014
Dulaglutide is a once-weekly injectable GLP-1 agonist designed primarily for Type 2 diabetes. It comes in a user-friendly, single-dose pen that requires no needle handling — the needle is hidden and automatically inserts when the pen is activated.
Dosing
| Brand | Route | Frequency | Indication | Dose Range |
|---|---|---|---|---|
| Trulicity | SC injection | Once weekly | Type 2 diabetes | 0.75-4.5 mg |
Key Efficacy Data
- HbA1c reduction: ~1.1-1.8% (dose-dependent)
- Weight loss: ~3-5 kg (moderate; less than semaglutide or tirzepatide)
- Cardiovascular benefit: 12% reduction in MACE (REWIND trial) — notable because it enrolled patients with cardiovascular risk factors, not just established CVD
Dulaglutide is specifically approved for reducing the risk of cardiovascular death in patients with Type 2 diabetes and established or at-risk CVD.
Exenatide (Byetta, Bydureon)
Manufacturer: AstraZeneca Mechanism: GLP-1 receptor agonist First approved: 2005 (Byetta), 2012 (Bydureon)
Exenatide was the first GLP-1 agonist approved by the FDA. Byetta requires twice-daily injection, while Bydureon BCise is a once-weekly extended-release formulation.
Dosing
| Brand | Route | Frequency | Indication | Dose Range |
|---|---|---|---|---|
| Byetta | SC injection | Twice daily | Type 2 diabetes | 5-10 mcg |
| Bydureon BCise | SC injection | Once weekly | Type 2 diabetes | 2 mg |
Key Efficacy Data
- HbA1c reduction: ~0.8-1.3%
- Weight loss: ~2-3 kg
- No proven cardiovascular benefit (neutral in the EXSCEL trial)
Exenatide is now considered a first-generation GLP-1 drug. It is less potent than semaglutide, tirzepatide, or dulaglutide for both glucose lowering and weight loss. However, it remains available and may be prescribed when newer agents are contraindicated or inaccessible.
Pediatric Use
Bydureon BCise is approved for patients aged 10 and older with Type 2 diabetes.
Lixisenatide (Adlyxin, Soliqua)
Manufacturer: Sanofi Mechanism: GLP-1 receptor agonist First approved: 2016 (Adlyxin), 2016 (Soliqua)
Lixisenatide is a short-acting, once-daily GLP-1 agonist primarily available in combination with insulin glargine (as Soliqua 100/33). It is less commonly used as a standalone agent.
Dosing
| Brand | Route | Frequency | Indication | Dose Range |
|---|---|---|---|---|
| Adlyxin | SC injection | Once daily | Type 2 diabetes | 10-20 mcg |
| Soliqua | SC injection (with insulin glargine) | Once daily | Type 2 diabetes | 15-60 mcg |
Key Efficacy Data
- HbA1c reduction: ~0.7-1.0% as monotherapy; greater in combination with insulin
- Weight loss: Minimal (~0.5-1 kg)
- No proven cardiovascular benefit (neutral in the ELIXA trial)
- Postprandial glucose: Strong effect on after-meal glucose spikes due to short-acting profile
Lixisenatide's primary clinical role is in combination with basal insulin for patients who need both fasting and postprandial glucose control.
Head-to-Head Efficacy Comparison
FDA-Approved Drugs: Weight Loss
| Drug | Dose | Weight Loss | Trial Duration | Trial |
|---|---|---|---|---|
| Tirzepatide | 15 mg weekly | -20.2% | 72 weeks | SURMOUNT-5 |
| Semaglutide (SC) | 2.4 mg weekly | -13.7% | 72 weeks | SURMOUNT-5 |
| Semaglutide (oral) | 50 mg daily | -12.7% | 68 weeks | OASIS 1 |
| Liraglutide | 3.0 mg daily | ~-8% | 56 weeks | SCALE |
| Dulaglutide | 4.5 mg weekly | ~-5% | 36 weeks | AWARD-11 |
| Exenatide ER | 2 mg weekly | ~-2.5% | 28 weeks | DURATION trials |
FDA-Approved Drugs: HbA1c Reduction
| Drug | Dose | HbA1c Reduction | Notes |
|---|---|---|---|
| Tirzepatide | 15 mg | -2.3% | SURPASS-2 |
| Semaglutide (SC) | 2 mg | -1.8% | SUSTAIN trials |
| Semaglutide (oral) | 14 mg | -1.3% | PIONEER trials |
| Dulaglutide | 4.5 mg | -1.8% | AWARD-11 |
| Liraglutide | 1.8 mg | -1.5% | LEAD trials |
| Exenatide ER | 2 mg | -1.3% | DURATION trials |
| Lixisenatide | 20 mcg | -0.9% | GetGoal trials |
Cardiovascular Outcomes
| Drug | CV Outcome | Risk Reduction | Trial |
|---|---|---|---|
| Semaglutide | MACE | 20% | SELECT |
| Liraglutide | MACE | 13% | LEADER |
| Dulaglutide | MACE | 12% | REWIND |
| Exenatide ER | MACE | Neutral | EXSCEL |
| Lixisenatide | MACE | Neutral | ELIXA |
| Tirzepatide | MACE | Trial ongoing (SURPASS-CVOT) | — |
Pipeline Drugs to Watch in 2026-2027
The next generation of GLP-1-based drugs is advancing rapidly. Here are the five most important pipeline drugs and their current data.
Orforglipron — The First Non-Peptide Oral GLP-1
Manufacturer: Eli Lilly Mechanism: Oral, non-peptide, small-molecule GLP-1 receptor agonist Status: NDA submitted to FDA; potential approval expected Q2 2026
Orforglipron could be the most disruptive drug in the GLP-1 class. Unlike oral semaglutide (which is a peptide requiring fasting), orforglipron is a small-molecule that can be taken without restrictions on food or water intake. Take it with breakfast. Take it with coffee. It does not matter.
Key Data
- Mechanism: Partial GLP-1 receptor agonist that preferentially activates cyclic AMP signaling over beta-arrestin recruitment, potentially reducing receptor desensitization
- HbA1c reduction (Phase 2): Up to -2.1% vs. -1.1% for dulaglutide and -0.43% for placebo
- Weight loss: Phase 3 data pending; Phase 2 showed significant weight reduction
- ATTAIN-MAINTAIN trial: Patients switching from semaglutide to orforglipron maintained previously achieved weight loss (average difference of 0.9 kg). Those switching from tirzepatide also maintained their weight loss (average difference of 5 kg)
Why It Matters
An effective oral GLP-1 that works without fasting requirements could dramatically expand the addressable market. Many patients resist injectable therapy. Oral semaglutide requires a 30-minute fast with just a sip of water. Orforglipron has none of these restrictions, making it the most patient-friendly GLP-1 option if approved.
Eli Lilly expects a starting price point that undercuts injectable GLP-1 drugs, potentially opening access to millions of additional patients.
Retatrutide — The Triple Agonist
Manufacturer: Eli Lilly Mechanism: Triple agonist of GIP, GLP-1, and glucagon receptors Status: Phase 3 (TRIUMPH program); first results reported December 2025
Retatrutide targets three metabolic hormone receptors simultaneously. GLP-1 reduces appetite and blood sugar. GIP amplifies these effects. Glucagon increases energy expenditure by promoting fat burning and thermogenesis. The triple mechanism produces the largest weight loss numbers ever seen in clinical trials.
Phase 3 Results (TRIUMPH-4)
| Endpoint | Retatrutide 9 mg | Retatrutide 12 mg | Placebo |
|---|---|---|---|
| Weight loss | -26.4% (-29.1 kg) | -28.7% (-32.3 kg) | -2.1% |
| Achieved >=25% loss | Not reported | 58.6% | — |
| Achieved >=30% loss | Not reported | 39.4% | — |
| Systolic BP reduction | Significant | -14.0 mmHg | — |
From a baseline average of 248.5 pounds, participants on the 12 mg dose lost an average of 71.2 pounds.
Safety Signals
The TRIUMPH-4 trial revealed a new safety concern: dysesthesia (abnormal sensory symptoms — tingling, numbness, or painful sensations). This affected 8.8% of the 9 mg group and 20.9% of the 12 mg group, compared to 0.7% on placebo. This signal was not seen in earlier trials.
Gastrointestinal side effects were substantial: nausea (43%), diarrhea (33%), and vomiting (21%). Discontinuation rates were 12.2% (9 mg) and 18.2% (12 mg), with some patients discontinuing due to "perceived excessive weight loss."
What's Next
Seven additional Phase 3 trials are expected to report results throughout 2026, covering obesity, Type 2 diabetes, sleep apnea, osteoarthritis, chronic low back pain, fatty liver disease, and cardiovascular outcomes. The TRIUMPH-1 trial, running for 80 weeks, could show weight loss exceeding 30%. Approval is projected for 2027.
CagriSema — Semaglutide Plus Amylin
Manufacturer: Novo Nordisk Mechanism: Fixed-dose combination of cagrilintide (long-acting amylin analog, 2.4 mg) and semaglutide (2.4 mg) Status: NDA filed with FDA (2025)
CagriSema pairs semaglutide with an amylin analog. Amylin, like GLP-1, is a hormone released after eating that slows gastric emptying and promotes satiety. The combination attacks appetite through two distinct hormonal pathways.
Phase 3 Results
REDEFINE 1 (without diabetes, 68 weeks):
| Outcome | CagriSema | Semaglutide alone | Cagrilintide alone | Placebo |
|---|---|---|---|---|
| Weight loss | -22.7%* | -14.9% | -11.5% | -3.0% |
| Achieved >=20% loss | 60% | — | — | — |
| Achieved >=25% loss | 40.4% | — | — | — |
| Achieved >=30% loss | 23% | — | — | — |
*Estimated on-treatment analysis (full adherence). Treatment-policy estimate was -20.4%.
Notably, 56.4% of CagriSema participants were no longer classified as obese by the end of the trial.
REDEFINE 2 (with Type 2 diabetes, 68 weeks):
- Weight loss: -15.7% (on-treatment) vs. -3.1% placebo
- HbA1c <=6.5%: Achieved by 73.5% of CagriSema vs. 15.9% of placebo participants
Safety Profile
Gastrointestinal adverse events occurred in 72.5% of CagriSema patients vs. 34.4% on placebo, but most were mild to moderate and transient. Discontinuation due to adverse events was approximately 6%.
Context
CagriSema missed Novo Nordisk's internal target of 25% weight loss, which caused a stock price drop. But its 22.7% result still makes it the second most effective anti-obesity therapy after retatrutide.
Ongoing trials include REDEFINE 4 (head-to-head vs. tirzepatide) and REDEFINE 3 (cardiovascular outcomes in 7,000 patients).
Survodutide — Glucagon/GLP-1 Dual Agonist
Manufacturer: Boehringer Ingelheim / Zealand Pharma Mechanism: Dual glucagon/GLP-1 receptor agonist (once-weekly SC injection) Status: Phase 3 (SYNCHRONIZE program); breakthrough therapy designation for MASH
Survodutide stands out for targeting the glucagon receptor alongside GLP-1. Glucagon receptor activation increases energy expenditure and drives fat mobilization from the liver — making survodutide particularly promising for metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH).
Key Data
- Weight loss (Phase 2): 14.9% at 46 weeks
- MASH improvement (Phase 2): 47% at 2.4 mg, 62% at 4.8 mg, and 43% at 6.0 mg achieved MASH resolution with no worsening of fibrosis (vs. 14% placebo)
- FDA designations: Fast Track and Breakthrough Therapy Designation for MASH with fibrosis
- EMA designation: Priority Medicine (PRIME) scheme for MASH
What's Next
The SYNCHRONIZE-1 (without diabetes) and SYNCHRONIZE-2 (with diabetes) Phase 3 trials are tracking weight loss over 76 weeks. Recruitment is complete, with primary completion expected in 2026.
MariTide — Monthly GLP-1/GIP Bispecific
Manufacturer: Amgen Mechanism: GLP-1 receptor agonist + GIP receptor antagonist (bispecific antibody-peptide conjugate) Status: Phase 2 completed; Phase 3 (MARITIME program) initiated
MariTide takes a fundamentally different approach. While tirzepatide activates both GLP-1 and GIP receptors, MariTide activates GLP-1 but blocks GIP. This opposite approach to GIP may produce more durable weight loss and reduce weight regain after stopping treatment.
Its other breakthrough is dosing frequency: once monthly (or potentially less often), compared to weekly for every other drug in the class.
Phase 2 Results (52 weeks)
Without Type 2 diabetes:
- Weight loss: 12.3% to 16.2% (intention-to-treat) and up to ~20% (on-treatment) — with no weight loss plateau at 52 weeks
- Weight continued trending downward, suggesting further loss beyond 52 weeks
With Type 2 diabetes:
- Weight loss: 8.4% to 12.3% (ITT)
- HbA1c reduction: Up to 2.2 percentage points
Safety
No new safety signals. Gastrointestinal events were mostly mild to moderate and concentrated during initial dosing. Dose escalation reduced GI discontinuation rates to 8% vs. 12-27% without escalation.
Results published in the New England Journal of Medicine in 2025. Phase 3 MARITIME program is now enrolling for 72-week chronic weight management trials.
Pricing and Access in 2026
The GLP-1 market is entering a new pricing era in 2026. Multiple factors are driving costs down.
Current Pricing Overview
| Drug | Monthly Cost (list price) | Monthly Cost (with discounts) |
|---|---|---|
| Ozempic | ~$900 | $200-500 with savings programs |
| Wegovy (injectable) | ~$1,300 | $300-600 with insurance |
| Wegovy (oral pill) | Starting at $149 | $149 (launch price) |
| Mounjaro | ~$1,050 | $200-500 with savings programs |
| Zepbound | ~$1,050 | $199 (Lilly Direct cash price) |
| Saxenda | ~$1,400 | Dropping (generic approved Aug 2025) |
| Trulicity | ~$850 | $200-400 with savings programs |
What's Changing in 2026
GLP-1 prices are expected to fall 28% in 2026, according to Morningstar Equity Research, driven by most-favored-nation pricing negotiations with the U.S. government.
Additional price pressure comes from:
- Generic liraglutide — First generic Saxenda approved August 2025
- Oral semaglutide for obesity — $149/month starting dose disrupts the price floor
- Orforglipron — Expected to launch at a competitive oral price point
- Medicare/Medicaid coverage expansion — Broader insurance coverage increases volume, enabling lower per-unit pricing
- Compounded alternatives — Though limited by FDA restrictions, compounded semaglutide has historically offered lower-cost access (typically $200-500/month)
By 2027-2028, as retatrutide, CagriSema, MariTide, and other competitors launch, further price declines are expected through market competition.
Expanding Indications Beyond Diabetes and Obesity
GLP-1 drugs are no longer viewed solely as diabetes or weight loss treatments. The class is expanding into multiple disease areas:
| Indication | Drug | Status |
|---|---|---|
| Cardiovascular risk reduction | Semaglutide, liraglutide, dulaglutide | Approved |
| Chronic kidney disease | Semaglutide (Ozempic) | Approved (Jan 2025) |
| Obstructive sleep apnea | Tirzepatide (Zepbound) | Approved (Late 2024) |
| MASH (fatty liver disease) | Survodutide | Phase 3 / Breakthrough Therapy |
| Heart failure (HFpEF) | Semaglutide (Wegovy) | Under FDA review |
| Peripheral artery disease | Semaglutide (Ozempic) | Under FDA review |
| Alzheimer's disease | Semaglutide | Phase 3 (potential approval late 2026) |
| Knee osteoarthritis | Retatrutide | Phase 3 (positive results Dec 2025) |
| Addiction | Semaglutide | Early-stage research |
| PCOS | Multiple GLP-1 drugs | Ongoing research |
The possibility that semaglutide could become the first GLP-1 drug approved for Alzheimer's disease by late 2026 would mark an extraordinary expansion of the class far beyond metabolic medicine. For more on this research, see our guide to GLP-1 agonists and neurodegeneration research.
Side Effects Across the Class
All GLP-1 drugs share a common side effect profile dominated by gastrointestinal symptoms. The rates vary by drug, dose, and individual tolerance.
Common Side Effects
| Side Effect | Frequency | Notes |
|---|---|---|
| Nausea | 15-45% | Most common; usually worst during dose escalation |
| Diarrhea | 10-35% | Varies by drug and dose |
| Vomiting | 5-25% | More common at higher doses |
| Constipation | 5-15% | Can alternate with diarrhea |
| Abdominal pain | 5-15% | Usually mild |
| Injection site reactions | 5-10% | For injectable formulations |
Serious but Rare Risks
- Pancreatitis: Reported in post-marketing surveillance; risk appears small but real. Patients with a history of pancreatitis should discuss risks with their doctor.
- Gallbladder disease: Rapid weight loss from any cause increases gallstone risk. GLP-1 drugs amplify this through their weight loss effects.
- Thyroid C-cell tumors: Box warning based on rodent studies. No confirmed human risk, but GLP-1 drugs are contraindicated in patients with personal or family history of medullary thyroid carcinoma or MEN 2.
- Gastroparesis: Severe slowing of stomach emptying has been reported in some patients, particularly at higher doses.
- Dysesthesia: A new signal specific to retatrutide (20.9% at the 12 mg dose). Not seen with other GLP-1 drugs.
- Muscle mass loss: Weight loss from GLP-1 drugs includes both fat and lean mass. The proportion of lean mass loss (~25-40% of total weight lost) is a growing concern, particularly for older adults. See our guide to GLP-1 agonists and muscle mass concerns.
Managing Side Effects
Most GI side effects improve with time. The standard approach is slow dose escalation — starting at the lowest dose and increasing every 4 weeks as tolerated. This strategy significantly reduces the severity and duration of nausea and vomiting.
Complete Comparison Table
Approved Drugs
| Drug | Brand(s) | Mechanism | Route | Frequency | Weight Loss | HbA1c | CV Benefit |
|---|---|---|---|---|---|---|---|
| Semaglutide | Ozempic, Wegovy, Rybelsus | GLP-1 | SC / Oral | Weekly / Daily | 13.7% | -1.8% | Yes |
| Tirzepatide | Mounjaro, Zepbound | GIP/GLP-1 | SC | Weekly | 20.2% | -2.3% | Trial pending |
| Liraglutide | Victoza, Saxenda | GLP-1 | SC | Daily | ~8% | -1.5% | Yes |
| Dulaglutide | Trulicity | GLP-1 | SC | Weekly | ~5% | -1.8% | Yes |
| Exenatide | Byetta, Bydureon | GLP-1 | SC | 2x daily / Weekly | ~2.5% | -1.3% | Neutral |
| Lixisenatide | Adlyxin, Soliqua | GLP-1 | SC | Daily | ~1% | -0.9% | Neutral |
Pipeline Drugs
| Drug | Company | Mechanism | Route | Frequency | Weight Loss | Status |
|---|---|---|---|---|---|---|
| Retatrutide | Eli Lilly | GIP/GLP-1/glucagon | SC | Weekly | 28.7% | Phase 3 |
| CagriSema | Novo Nordisk | GLP-1 + amylin | SC | Weekly | 22.7% | NDA filed |
| Orforglipron | Eli Lilly | GLP-1 (small molecule) | Oral | Daily | TBD | NDA submitted |
| Survodutide | Boehringer/Zealand | GLP-1/glucagon | SC | Weekly | 14.9% | Phase 3 |
| MariTide | Amgen | GLP-1 agonist/GIP antagonist | SC | Monthly | ~20% | Phase 2/3 |
The Bottom Line
The GLP-1 drug class in 2026 is no longer a two-horse race. While semaglutide and tirzepatide dominate the current market, the pipeline drugs approaching approval represent the next era of metabolic medicine.
For patients with Type 2 diabetes seeking the best HbA1c control and weight loss, tirzepatide currently offers the strongest combination of both. Semaglutide remains the most versatile option with the widest range of approved indications and both injectable and oral formulations.
For weight management alone, tirzepatide's 20.2% weight loss surpasses semaglutide's 13.7% in direct comparison. The pipeline drugs push even further — retatrutide at 28.7% and CagriSema at 22.7%.
For patients who want to avoid injections, oral semaglutide is available now. Orforglipron, if approved in 2026, will offer a more convenient oral option without fasting restrictions.
For cost-conscious patients, the picture is improving. Prices are expected to drop 28% in 2026, generic liraglutide is now available, and the oral semaglutide pill starts at $149/month.
The choice of GLP-1 drug should be made with a healthcare provider who can evaluate your specific medical history, goals, insurance coverage, and tolerance for side effects. The best drug for you is the one that balances efficacy, convenience, affordability, and tolerability for your individual situation.
References
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Jastreboff AM, et al. "Tirzepatide as Compared with Semaglutide for the Treatment of Obesity." New England Journal of Medicine. 2025. https://www.nejm.org/doi/full/10.1056/NEJMoa2416394
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Frias JP, et al. "Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes." New England Journal of Medicine. 2021. https://www.nejm.org/doi/full/10.1056/NEJMoa2107519
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