Every GLP-1 Drug Ranked by Effectiveness, Using Trial Data

Search for a GLP-1 ranking and you will find a dozen charts that all disagree. Most are assembled by lining up numbers from separate trials that studied different people for different lengths of time, which is a bit like ranking runners by comparing races they never ran together.

This article does something narrower and more honest. It ranks the incretin drugs approved in the US using published trial results, and it tells you which parts of the ranking rest on real head-to-head trials and which parts are cross-trial estimates that could be wrong.

Nothing here is medical advice. A ranking cannot tell you which drug belongs in your life. That is a conversation with a healthcare provider, and the strongest drug on paper is often not the right one for a particular person.

What does “effective” actually mean here?

These drugs get measured on two different scoreboards, and a drug can look very different on each.

Blood sugar. In type 2 diabetes, the standard measure is how far a drug lowers A1C, a blood test that reflects average blood sugar over about three months. A drop of 1 percentage point is meaningful. A drop of 2 points is a lot.

Body weight. In obesity trials, the measure is the average percent of starting body weight lost, usually at 56 to 72 weeks.

There is a third scoreboard that gets less attention and arguably matters more: cardiovascular outcomes, meaning whether a drug reduces heart attacks, strokes and cardiovascular deaths in a large, long trial. A drug can lower A1C nicely and still show nothing here.

One more thing to know before the numbers. Trials report results using different “estimands” — statistical rules for how to count people who quit the study or start other medicines. The “efficacy” or “trial product” estimand asks what happens to people who stay on the drug. The “treatment policy” or “treatment regimen” estimand counts everyone regardless. The second number is always smaller and always more realistic. Where this matters below, it is flagged.

Which GLP-1 causes the most weight loss?

Here is the weight ranking, best first, with the trial behind each number.

1. Tirzepatide (Zepbound, Mounjaro) — about 20 percent. In SURMOUNT-1, adults with obesity and without diabetes lost an average of 15.0 percent at 5 mg, 19.5 percent at 10 mg and 20.9 percent at 15 mg over 72 weeks, against 3.1 percent on placebo [1]. Tirzepatide is not a pure GLP-1; it also activates the GIP receptor, which is widely thought to be why it does more.

2. Semaglutide 2.4 mg (Wegovy) — about 14 to 15 percent. In STEP 1, the average weight change at 68 weeks was 14.9 percent versus 2.4 percent on placebo, with 69.1 percent of participants losing at least 10 percent of their body weight [2].

These top two are the only pair with a direct comparison. SURMOUNT-5 randomized 751 adults with obesity and without diabetes to one or the other for 72 weeks. Tirzepatide produced a 20.2 percent average reduction; semaglutide 2.4 mg produced 13.7 percent [3]. Same patients, same clock, same protocol. That is the single most reliable comparison in this whole article.

3. Orforglipron (Foundayo) — about 12 percent. Lilly’s once-daily small-molecule GLP-1 tablet was approved on April 1, 2026 for adults with obesity, or overweight with a weight-related condition, alongside a reduced-calorie diet and increased physical activity [4]. It is not a peptide, which is why it has no food or water timing restrictions. In ATTAIN-1, 3,127 adults with obesity and without diabetes on the highest dose lost an average of 12.4 percent at 72 weeks versus 0.9 percent on placebo, using the efficacy estimand; counting everyone regardless of whether they stayed on treatment, it was 11.2 percent versus 2.1 percent [5]. There is no head-to-head against any injectable, and ATTAIN-1 used a balanced healthy diet rather than a reduced-calorie diet as its backdrop, so its placebo arm behaved differently from the STEP and SURMOUNT placebo arms. Treat its position as an estimate.

4. Liraglutide 3.0 mg (Saxenda and its generics) — about 6 to 8 percent. In the SCALE Obesity and Prediabetes trial, participants lost an average of 8.4 kg versus 2.8 kg on placebo at 56 weeks [6]. When liraglutide was put directly against semaglutide 2.4 mg in STEP 8, it managed 6.4 percent over 68 weeks against semaglutide’s 15.8 percent — a 9.4 percentage point gap [7]. In that trial 70.9 percent of the semaglutide group lost at least 10 percent of their weight, versus 25.6 percent of the liraglutide group.

Nothing else is on this list, because nothing else is approved in the US for weight management. Trulicity, Victoza, Ozempic, exenatide and the insulin combinations are all diabetes drugs. People do lose weight on them, and that weight loss appears in the diabetes trials below, but it is a secondary effect and not an approved use.

Which GLP-1 lowers A1C the most?

This is a different ranking, and the order is not identical.

1. Tirzepatide. In SURPASS-2, 1,879 adults with type 2 diabetes were randomized to tirzepatide 5, 10 or 15 mg or to semaglutide 1 mg for 40 weeks. A1C fell 2.01, 2.24 and 2.30 percentage points with tirzepatide versus 1.86 with semaglutide, and all three tirzepatide doses were statistically superior. Weight fell more too, by an extra 1.9 kg, 3.6 kg and 5.5 kg respectively [8].

2. Semaglutide injection (Ozempic). In SUSTAIN 7, semaglutide 1.0 mg lowered A1C by 1.8 points over 40 weeks [9]. In SUSTAIN 10, semaglutide 1.0 mg lowered it by 1.7 points from a baseline of 8.2 percent [10].

3. Dulaglutide (Trulicity) at its higher doses. AWARD-11 tested the 3 mg and 4.5 mg doses that were added to the label in 2020. At 36 weeks, A1C fell 1.77 points on 4.5 mg versus 1.54 on 1.5 mg — a gain of about a quarter of a point for triple the dose, along with 1.6 kg more weight loss [11].

4. Liraglutide (Victoza). In AWARD-6, liraglutide 1.8 mg lowered A1C by 1.36 points at 26 weeks, statistically tied with dulaglutide 1.5 mg at 1.42 points [12]. In DURATION-6 it managed 1.48 points [13].

5. Dulaglutide 1.5 mg. In SUSTAIN 7 it produced 1.4 points, clearly behind semaglutide 1.0 mg’s 1.8 [9].

6. Oral semaglutide 14 mg (the old Rybelsus). In PIONEER 4 it lowered A1C by 1.2 points at 26 weeks, statistically noninferior to injected liraglutide 1.8 mg at 1.1 points, and it beat liraglutide on weight loss, 4.4 kg versus 3.1 kg [14]. The 2026 Ozempic tablets are a reformulation of the same molecule with better absorption, and Novo Nordisk has filed for a 25 mg strength with an FDA decision expected by the end of 2026.

7. Exenatide extended-release (Bydureon). In DURATION-6 it lowered A1C by 1.28 points, less than liraglutide’s 1.48, and it failed to meet the trial’s noninferiority criteria [13]. It was better tolerated, with nausea in 9 percent versus 21 percent.

8. Exenatide twice daily (Byetta and its generic). The oldest drug in the class, and a short-acting one, so its effect is concentrated around meals rather than spread across the day.

Lixisenatide (Adlyxin, and the GLP-1 half of Soliqua) is also short-acting and mainly blunts after-meal glucose spikes. It has no US brand of its own any more; it survives only inside Soliqua 100/33.

Which GLP-1s actually protect the heart?

This scoreboard scrambles the ranking, and it is the one that guidelines care about most.

Drug	Trial	Result
Liraglutide	LEADER, 9,340 patients, 3.8 years	Major cardiovascular events reduced, hazard ratio 0.87 (0.78–0.97); cardiovascular death hazard ratio 0.78 [15]
Dulaglutide	REWIND, 9,901 patients, 5.4 years	Hazard ratio 0.88 (0.79–0.99), driven mainly by fewer strokes [16]
Albiglutide	Harmony Outcomes, 9,463 patients, 1.6 years	Hazard ratio 0.78 (0.68–0.90) — a positive trial for a drug already pulled from the market [17]
Exenatide extended-release	EXSCEL, 14,752 patients, 3.2 years	Hazard ratio 0.91 (0.83–1.00), p = 0.06 for superiority — a near miss [18]
Lixisenatide	ELIXA, 6,068 patients, about 2 years	Hazard ratio 1.02 (0.89–1.17) — safe, but no benefit [19]

Two things jump out. First, liraglutide — a drug that loses badly on the weight and A1C scoreboards — has one of the strongest cardiovascular records in the class, including a reduction in cardiovascular death. Second, exenatide and lixisenatide, the two exendin-based drugs, are the two that showed nothing. That pattern is a real part of why the exendin drugs lost the market they created.

What is the honest ranking, all things considered?

Putting the scoreboards together, here is where the evidence lands as of September 2026:

1. Tirzepatide — strongest on weight and A1C, with direct head-to-head wins over semaglutide on both.
2. Semaglutide injection — second on both scoreboards, with direct wins over dulaglutide and liraglutide, plus cardiovascular and kidney indications.
3. Oral semaglutide — same molecule, less of it absorbed; roughly liraglutide-level on A1C in PIONEER 4 but better on weight.
4. Orforglipron — strong for a pill, roughly between liraglutide and injected semaglutide on weight, but with no head-to-head evidence.
5. Dulaglutide — close to liraglutide on A1C, better on convenience, with a solid long-term cardiovascular trial.
6. Liraglutide — weaker on weight and A1C, strongest per-dollar, and with the best cardiovascular mortality data in the class.
7. Exenatide — outperformed on every scoreboard, now gone as a brand.
8. Lixisenatide — neutral cardiovascular data, no standalone US product left.

Why do the cheap older drugs still get prescribed?

Because effectiveness rankings do not pay for prescriptions.

Generic liraglutide costs roughly $288 a month for the diabetes version at pharmacy acquisition cost — $32.00 per mL for the three-pack, effective August 19, 2026, in the National Average Drug Acquisition Cost survey — against roughly $975 for Trulicity and $996 for an Ozempic pen at the same date [20]. That is not a patient price — it ignores rebates and copays — but it is the closest thing to an apples-to-apples public benchmark, and the gap is enormous.

Most US commercial plans also require you to try metformin at the maximum tolerated dose before covering any GLP-1 for type 2 diabetes, and then designate a short list of preferred agents. Where a cheap generic exists, plans have every reason to put it first. A drug that works 60 percent as well but that your plan actually covers, at a copay you can sustain for years, can deliver more real-world benefit than a stronger drug you abandon after three months.

What should you take away from this?

Three things.

Head-to-head evidence is worth far more than a chart. SURMOUNT-5, SUSTAIN 7, STEP 8, AWARD-6, PIONEER 4, SURPASS-2 and DURATION-6 are the trials that actually put two drugs in the same room. Everything else on any ranking chart, including parts of this one, is inference.

Averages hide enormous individual variation. In STEP 8, some people on semaglutide lost more than 20 percent of their body weight and some lost almost nothing. Your result will not be the trial average.

Tolerability decides more outcomes than potency. In STEP 8, 27.6 percent of the liraglutide group stopped treatment for some reason, against 13.5 percent on semaglutide [7]. A drug you stop taking has an effectiveness of zero.

If you are trying to decide between these, bring specifics to a healthcare provider: your A1C and weight history, what you have tried, what side effects you have had, whether heart or kidney disease is in the picture, and what your insurance actually covers.

Every dose and result quoted above comes from a published trial or an FDA-approved label, not from a recommendation. Dosing in practice is set by a prescription and the FDA-approved Instructions for Use that ship with each product. On combining agents, the published switching guidance is explicit that two GLP-1 receptor agonists should not be taken together, and the fixed-ratio insulin combination labels require any prior GLP-1 to be discontinued before the new product is started [21].

Sources

1. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1), New England Journal of Medicine, 2022
2. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1), New England Journal of Medicine, 2021
3. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5), New England Journal of Medicine, 2025
4. FDA approves Lilly’s Foundayo (orforglipron), the only GLP-1 pill for weight loss, Eli Lilly and Company, April 1, 2026
5. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment (ATTAIN-1), New England Journal of Medicine, 2025
6. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management (SCALE), New England Journal of Medicine, 2015
7. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight (STEP 8), JAMA, 2022
8. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes (SURPASS-2), New England Journal of Medicine, 2021
9. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7), The Lancet Diabetes & Endocrinology, 2018
10. Efficacy and safety of once-weekly semaglutide 1.0 mg vs once-daily liraglutide 1.2 mg (SUSTAIN 10), Diabetes & Metabolism, 2020
11. Efficacy and Safety of Dulaglutide 3.0 mg and 4.5 mg Versus Dulaglutide 1.5 mg (AWARD-11), Diabetes Care, 2021
12. Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6), The Lancet, 2014
13. Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6), The Lancet, 2013
14. Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4), The Lancet, 2019
15. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes (LEADER), New England Journal of Medicine, 2016
16. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND), The Lancet, 2019
17. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes (Harmony Outcomes), The Lancet, 2018
18. Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes (EXSCEL), New England Journal of Medicine, 2017
19. Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome (ELIXA), New England Journal of Medicine, 2015
20. NADAC (National Average Drug Acquisition Cost), Centers for Medicare & Medicaid Services, values effective August 19, 2026
21. Switching Between Glucagon-Like Peptide-1 Receptor Agonists: Rationale and Practical Guidance, Clinical Diabetes, 2020