GLP-1 Drugs Ranked by Effectiveness: Weight and A1C Results
Tirzepatide ranks first on both scoreboards: -20.9% body weight in SURMOUNT-1 and a 2.30-point A1C drop that beat semaglutide head to head. Injectable semaglutide is second, the orforglipron pill third on weight, liraglutide fourth. Direct trials back the top spots; the heart-protection scoreboard reshuffles the order.
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On weight, tirzepatide (Zepbound, Mounjaro) ranks first among the medicines with published obesity trials: people taking its highest trial dose lost an average of 20.9% of body weight over 72 weeks [1], and tirzepatide beat semaglutide head to head, 20.2% versus 13.7% [3]. On blood sugar, tirzepatide also leads the head-to-head record, lowering A1C by 2.30 points versus 1.86 points for semaglutide 1 mg in SURPASS-2 [8]. Injectable semaglutide (Wegovy, Ozempic) holds second place on both lists, the orforglipron pill (Foundayo) sits third on weight, and liraglutide (Victoza, Saxenda) fourth [1][2][5][6]. One caveat on the winner: tirzepatide is a dual GIP and GLP-1 receptor agonist, not a pure GLP-1 [1][8].
How sure can we be about that order? The top spots rest on direct head-to-head trials. The middle and bottom mix direct comparisons with cross-trial inference, which is weaker. And a third scoreboard — heart attacks, strokes, and cardiovascular death — reshuffles the ranking entirely, because the drugs that lose on weight and A1C hold some of the only clear wins there [15][17].
Why most GLP-1 ranking charts mislead
Most charts line up numbers from trials that were never designed to be compared. The big obesity trials ran for different lengths: SCALE lasted 56 weeks, STEP 1 ran 68 weeks, and SURMOUNT-1 and ATTAIN-1 ran 72 weeks [6][2][1][5]. A drug tested for four extra months has more time to shed weight, so raw percentages are not apples to apples.
The second trap is the estimand, the rule for who gets counted. A treatment-regimen estimand counts everyone who was randomized, regardless of whether they stopped the drug or needed rescue treatment. An efficacy estimand counts only people still on treatment without rescue medication. AWARD-11 reports both, and the two can give different answers for the same comparison [11][1][14].
The third trap is comparing across trials at all. The strongest evidence is direct head-to-head randomization, and the source list contains several: SURMOUNT-5, STEP 8, SURPASS-2, SUSTAIN 10, AWARD-6, DURATION-6, PIONEER 4, and SUSTAIN-7 (reported through a review table) [3][7][8][10][12][13][14][21].
What each trial actually measures
There are three different scoreboards, and a drug that wins one does not automatically win the others.
Obesity trials use two coprimary endpoints: the percent change in body weight and the share of people losing at least 5% of baseline weight [1][2]. Diabetes trials measure change in glycated hemoglobin (A1C) as the primary endpoint, on different clocks — SURPASS-2 at 40 weeks, AWARD-6 at 26 weeks [8][12]. Cardiovascular outcome trials use a composite of cardiovascular death, nonfatal heart attack, or nonfatal stroke, tested first against a noninferiority margin with a hazard ratio of 1.30 [15][17].
Which GLP-1 loses the most weight?
The weight ranking below covers the US-approved weight-management agents with obesity trials in the sources. All four trials enrolled adults without diabetes, so the populations are broadly comparable, though the trial lengths differ.
| Agent (trial arm) | Trial | Length | Mean weight change | Placebo group |
|---|---|---|---|---|
| Tirzepatide 15 mg | SURMOUNT-1 | 72 weeks | -20.9% | -3.1% [1] |
| Semaglutide 2.4 mg | STEP 1 | 68 weeks | -14.9% | -2.4% [2] |
| Orforglipron 36 mg | ATTAIN-1 | 72 weeks | -11.2% | -2.1% [5] |
| Liraglutide 3.0 mg | SCALE | 56 weeks | -8.4 kg | -2.8 kg [6] |
SURMOUNT-1 randomized 2,539 adults with a BMI of 30 or more, or 27 or more with a weight-related complication, none with diabetes [1]. Mean weight change at 72 weeks was -15.0% on the 5 mg arm, -19.5% on 10 mg, and -20.9% on 15 mg, all by the treatment-regimen estimand [1]. In the 15 mg group, 91% lost at least 5% of body weight and 57% lost 20% or more, versus 3% of placebo patients losing 20% or more [1].
STEP 1 enrolled 1,961 adults without diabetes and ran 68 weeks: -14.9% with semaglutide 2.4 mg versus -2.4% with placebo, a treatment difference of -12.4 percentage points [2]. In kilograms that was -15.3 kg versus -2.6 kg, and 86.4% of the semaglutide group lost at least 5%, 69.1% at least 10%, and 50.5% at least 15% [2].
ATTAIN-1 randomized 3,127 adults with obesity, none with diabetes, to orforglipron 6, 12, or 36 mg or placebo for 72 weeks, alongside a healthy diet and physical activity [5]. By the treatment-regimen estimand, weight change was -7.5%, -8.4%, and -11.2% versus -2.1% on placebo; on the 36 mg arm, 54.6% lost at least 10% and 18.4% lost at least 20% [5].
SCALE randomized 3,731 patients without type 2 diabetes and ran 56 weeks: -8.4 kg with liraglutide 3.0 mg versus -2.8 kg with placebo, a difference of -5.6 kg; 63.2% versus 27.1% lost at least 5%, and 33.1% versus 10.6% lost more than 10% [6].
Is tirzepatide really better than semaglutide for weight loss?
Yes, by the one direct comparison published. SURMOUNT-5 randomized 751 adults with obesity, none with diabetes, in an open-label design for 72 weeks, comparing the maximum tolerated dose of tirzepatide (10 or 15 mg) against the maximum tolerated dose of semaglutide (1.7 or 2.4 mg) [3].
At week 72, the tirzepatide group lost a mean 20.2% of body weight versus 13.7% with semaglutide, and waist circumference fell 18.4 cm versus 13.0 cm; tirzepatide was superior on both [3]. Because both arms used maximum tolerated doses and participants knew their assignment, the trial answers a practical question — which drug performed better when pushed to what people could actually take — rather than a fixed-dose question [3].
How does the orforglipron pill compare with the injections?
Foundayo (orforglipron) was FDA approved on April 1, 2026 for adults with obesity, or overweight with weight-related problems. It is a once-daily small-molecule, non-peptide pill that can be taken any time of day without food or water restrictions [4].
Its weight results trail the injectables. The 11.2% figure for the highest ATTAIN-1 dose is the treatment-regimen estimate, counting everyone randomized [5]. Lilly’s press materials quote a different number, 12.4% (27.3 lb) versus 0.9% on placebo, which counts only people who stayed on treatment; counting everyone regardless of completion, Lilly rounds the same result to 11.1% (25 lb) versus 2.1% [4]. The two figures answer different questions, so a chart that mixes them inflates the pill’s results.
The listed evidence for orforglipron is placebo-controlled; no head-to-head trial against another GLP-1 appears in the sources here, so its exact position between semaglutide and liraglutide is an inference, not a measured result [5]. Adverse events led 5.3% to 10.3% of orforglipron patients to stop treatment, versus 2.7% on placebo [5].
Did liraglutide ever win a weight comparison?
Not against semaglutide. STEP 8 randomized 338 adults without diabetes at 19 US sites over 68 weeks, comparing weekly semaglutide 2.4 mg against daily liraglutide 3.0 mg [7]. Mean weight change was -15.8% versus -6.4%, a difference of 9.4 percentage points, with pooled placebo at -1.9% [7].
The responder gaps were wide: at least 10% weight loss in 70.9% versus 25.6%, at least 15% in 55.6% versus 12.0%, and at least 20% in 38.5% versus 6.0% [7].
Which GLP-1 lowers A1C the most?
Tirzepatide, by the direct record. SURPASS-2 randomized 1,879 patients with type 2 diabetes (mean baseline A1C 8.28%, mean weight 93.7 kg) in an open-label 40-week trial [8]. A1C fell 2.01, 2.24, and 2.30 points on tirzepatide 5, 10, and 15 mg versus 1.86 points on semaglutide 1 mg — differences of -0.15, -0.39, and -0.45 points, with tirzepatide superior at every dose [8]. Weight also favored tirzepatide by 1.9 to 5.5 kg [8].
The rest of the A1C order, from the head-to-head trials:
| Trial | Comparison | A1C result |
|---|---|---|
| SURPASS-2 | tirzepatide 15 mg vs semaglutide 1 mg | -2.30 vs -1.86 points [8] |
| SUSTAIN 10 | semaglutide 1.0 mg vs liraglutide 1.2 mg | -1.7 vs -1.0 points from baseline 8.2% [10] |
| SUSTAIN-3 | semaglutide 1 mg vs exenatide 2 mg weekly | difference -0.62 points [21] |
| SUSTAIN-7 | semaglutide 1 mg vs dulaglutide 1.5 mg | difference -0.41 points [21] |
| AWARD-11 | dulaglutide 4.5 mg vs 1.5 mg | -1.77 vs -1.54 points [11] |
| AWARD-6 | dulaglutide 1.5 mg vs liraglutide 1.8 mg | -1.42 vs -1.36, tied [12] |
| PIONEER 4 | oral semaglutide 14 mg vs liraglutide 1.8 mg | -1.2 vs -1.1, noninferior [14] |
| DURATION-6 | liraglutide 1.8 mg vs exenatide 2 mg weekly | -1.48 vs -1.28 points [13] |
SUSTAIN-7 ran 40 weeks on a metformin background: semaglutide 1 mg beat dulaglutide 1.5 mg by 0.41 A1C points and 3.55 kg of weight, and the lower-dose pairing showed the same pattern [21]. SUSTAIN 10 ran 30 weeks in 577 adults: semaglutide 1.0 mg cut A1C by 1.7 points versus 1.0 for liraglutide 1.2 mg, and weight by 5.8 kg versus 1.9 kg [10].
In the middle of the pack, AWARD-11 tested 1,842 metformin-treated patients (baseline A1C 8.6%) and found dulaglutide 4.5 mg superior to 1.5 mg at 36 weeks (-1.77 vs -1.54 points, difference -0.24; weight -4.6 vs -3.0 kg), while the 3.0 mg dose was not superior on the treatment-regimen estimand [11]. AWARD-6 tied dulaglutide 1.5 mg with liraglutide 1.8 mg (-1.42 vs -1.36 points, difference -0.06, noninferior), with 6% of each group discontinuing for adverse events [12]. PIONEER 4 found oral semaglutide 14 mg noninferior to injected liraglutide 1.8 mg on A1C (-1.2 vs -1.1 points) but ahead on weight (-4.4 vs -3.1 kg) at 26 weeks [14]. At the bottom, DURATION-6 found liraglutide 1.8 mg ahead of weekly exenatide 2 mg (-1.48 vs -1.28 points), though exenatide caused less nausea, 9% versus 21% [13].
Why do the older drugs sit at the bottom?
Chemistry and half-life explain much of the order. Dulaglutide, liraglutide, and semaglutide are human GLP-1 analogs; exenatide and lixisenatide are exendin-based, derived from animal peptide, and albiglutide was withdrawn for commercial reasons, not safety [21].
Half-lives differ widely: exenatide 2.4 hours (dosed twice daily), lixisenatide about 3 hours (once daily), liraglutide about 13 hours, dulaglutide about 5 days, semaglutide about 7 days, and exenatide extended release 7 to 14 days [21]. In general, long-acting agents show greater effects on A1C, fasting glucose, and body weight than short-acting ones [21].
Dosing conditions add friction: twice-daily exenatide and once-daily lixisenatide must be taken within 1 hour before eating, while liraglutide and the weekly agents can be taken any time of day [21]. Oral semaglutide must be taken on an empty stomach with no more than 4 fl oz of water, at least 30 minutes before food [21]. Lixisenatide is available as a fixed-ratio combination with insulin glargine 100 units/mL [21].
Which GLP-1 has proven heart protection?
This scoreboard favors different drugs. LEADER followed 9,340 patients with type 2 diabetes for a median 3.8 years: the primary composite (cardiovascular death, nonfatal heart attack, nonfatal stroke) hit 13.0% on liraglutide versus 14.9% on placebo, hazard ratio 0.87 (95% CI 0.78 to 0.97), with cardiovascular death at HR 0.78 and death from any cause at HR 0.85 [15].
Harmony Outcomes tested albiglutide in 9,463 patients with cardiovascular disease over a median 1.6 years and found superiority, HR 0.78 (0.68 to 0.90) — though the drug was later withdrawn for commercial reasons [17][21]. EXSCEL followed 14,752 patients on weekly exenatide for a median 3.2 years: HR 0.91 (0.83 to 1.00), noninferior but not superior (P=0.06) [18]. ELIXA, in 6,068 patients with recent acute coronary syndrome followed a median 25 months, found HR 1.02 (0.89 to 1.17) — noninferior, with no benefit shown [19].
Guidelines respond to this split: in type 2 diabetes with atherosclerotic cardiovascular disease or chronic kidney disease, a GLP-1 receptor agonist or SGLT2 inhibitor with proven cardiovascular benefit is recommended first line for reducing cardiovascular risk [21].
How firm is each position in the ranking?
Tirzepatide’s first place is the firmest: direct wins over semaglutide on weight in SURMOUNT-5 and on A1C in SURPASS-2 [3][8]. Injectable semaglutide’s second place is also direct — wins over dulaglutide (SUSTAIN-7), liraglutide (STEP 8 on weight, SUSTAIN 10 on A1C and weight), and weekly exenatide (SUSTAIN-3) [21][7][10].
Below that, the evidence thins. Oral semaglutide 14 mg tied liraglutide 1.8 mg on A1C and beat it on weight in PIONEER 4, but it has not been compared head to head with injectable semaglutide in the sources here [14]. Orforglipron’s position rests on placebo-controlled data only [5]. Dulaglutide and liraglutide tied on A1C in AWARD-6 [12], and liraglutide finished ahead of weekly exenatide in DURATION-6 [13].
Does staying on treatment change the picture?
Yes, because the trial averages assume people keep taking the drug. In STEP 8, 13.5% of the semaglutide group stopped treatment for any reason versus 27.6% on liraglutide, while gastrointestinal adverse events were nearly identical at 84.1% versus 82.7% [7]. In SURMOUNT-1, adverse events caused 4.3%, 7.1%, and 6.2% of the tirzepatide dose groups to discontinue versus 2.6% on placebo [1]. In STEP 1, gastrointestinal events drove 4.5% of the semaglutide group off treatment versus 0.8% on placebo [2]. In SUSTAIN 10, 11.4% of the semaglutide group discontinued for adverse events versus 6.6% on liraglutide, with GI disorders in 43.9% versus 38.3% [10].
Real-world persistence is its own issue: pharmacy data suggest up to one-fourth of patients switch from their initial GLP-1 receptor agonist to another glucose-lowering agent after the first year, with cost and insurance among the reasons [21]. One label fact matters for anyone considering the pill: Foundayo should not be used with other GLP-1 receptor agonist medicines [4].
What do the sources say about cost and access?
The clearest published figures are manufacturer program prices for Foundayo, not list prices: with commercial insurance and a savings card, as little as $25 per month; self-pay starting at $149 per month for the lowest dose; and $50 per month for eligible Medicare Part D patients beginning as soon as July 1, 2026 [4].
On availability, Foundayo is sold through LillyDirect, with prescriptions accepted immediately and shipping beginning April 6, followed shortly after by broad availability through US retail pharmacies and telehealth providers [4].
Guidelines position GLP-1 receptor agonists as second-line therapy after metformin when glucose is not controlled, or first line when metformin cannot be used [21]. Insurance preference can override the efficacy ranking in practice — the switching review notes weekly exenatide could be tried when it is an insurance-preferred GLP-1 receptor agonist [21]. For comparing pharmacy-level costs across drugs, NADAC is a weekly national average drug acquisition cost reference dataset, updated September 8, 2026 [20].
Which agent fits a particular person depends on weight goals, blood sugar, heart and kidney health, tolerability, and coverage — a decision to work through with a healthcare provider rather than a ranking chart.
Sources
- PubMed. Tirzepatide Once Weekly for the Treatment of Obesity.
- PubMed. Once-Weekly Semaglutide in Adults with Overweight or Obesity.
- PubMed. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity.
- Eli Lilly and Company. FDA approves Lilly’s Foundayo (orforglipron), the only GLP-1 pill for weight loss that can be taken any time of day without food or water restrictions. April 1, 2026.
- PubMed. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment.
- PubMed. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management.
- PubMed. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial.
- PubMed. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes.
- The Lancet Diabetes & Endocrinology. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial.
- PubMed. Efficacy and safety of once-weekly semaglutide 1.0mg vs once-daily liraglutide 1.2mg as add-on to 1-3 oral antidiabetic drugs in subjects with type 2 diabetes (SUSTAIN 10).
- PubMed Central. Efficacy and Safety of Dulaglutide 3.0 mg and 4.5 mg Versus Dulaglutide 1.5 mg in Metformin-Treated Patients With Type 2 Diabetes in a Randomized Controlled Trial (AWARD-11).
- PubMed. Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): a randomised, open-label, phase 3, non-inferiority trial.
- PubMed. Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomised, open-label study.
- PubMed. Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): a randomised, double-blind, phase 3a trial.
- PubMed. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes.
- The Lancet. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial.
- PubMed. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial.
- PubMed. Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.
- PubMed. Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome.
- Medicaid.gov. NADAC (National Average Drug Acquisition Cost) 2026. Updated September 8, 2026.
- PubMed Central. Switching Between Glucagon-Like Peptide-1 Receptor Agonists: Rationale and Practical Guidance.
Frequently asked questions
Which GLP-1 is strongest for weight loss?
Tirzepatide, by the published trials. In SURMOUNT-1, its highest trial dose produced a mean weight change of -20.9% over 72 weeks, versus -3.1% on placebo. In the one direct comparison, tirzepatide beat semaglutide 20.2% to 13.7% at 72 weeks. Note that tirzepatide is a dual GIP and GLP-1 receptor agonist, not a pure GLP-1.
Is Mounjaro or Zepbound better than Ozempic or Wegovy, and by how much?
On the direct evidence, yes. SURMOUNT-5 compared maximum tolerated doses in adults with obesity and found -20.2% weight with tirzepatide versus -13.7% with semaglutide, a 6.5-point gap, plus a larger waist reduction. On blood sugar, SURPASS-2 found tirzepatide 15 mg lowered A1C 0.45 points more than semaglutide 1 mg.
How does the orforglipron pill compare with the injections?
The pill lost less weight in its trial: -11.2% at the highest ATTAIN-1 dose over 72 weeks versus -2.1% on placebo, by the treatment-regimen estimate. Lilly's 12.4% figure counts only people who stayed on treatment. The listed orforglipron evidence is placebo-controlled, with no head-to-head trial against another GLP-1 in these sources, so its exact rank is inferred.
Which GLP-1 lowers A1C the most?
Tirzepatide, in the head-to-head record. SURPASS-2 found A1C reductions of 2.01 to 2.30 points across tirzepatide doses versus 1.86 points with semaglutide 1 mg, with tirzepatide superior at every dose. Injectable semaglutide follows, with direct wins over dulaglutide, liraglutide, and weekly exenatide.
Trulicity vs Victoza: which works better?
On blood sugar, they tied. AWARD-6 compared weekly dulaglutide 1.5 mg with daily liraglutide 1.8 mg in 599 patients and found A1C reductions of 1.42 versus 1.36 points, a difference of only 0.06, meeting noninferiority. Adverse-event discontinuation was 6% in each group.
Which GLP-1 has proven heart protection?
Liraglutide and albiglutide. LEADER found the primary composite in 13.0% versus 14.9% on placebo, HR 0.87. Harmony Outcomes found albiglutide superior, HR 0.78, though it was later withdrawn for commercial reasons. Weekly exenatide and lixisenatide proved noninferior but not superior.
Why is liraglutide still prescribed if it loses on weight and A1C?
It holds the clearest cardiovascular win in LEADER, where cardiovascular death also fell, HR 0.78. Guidelines recommend a GLP-1 receptor agonist with proven cardiovascular benefit first line in type 2 diabetes with atherosclerotic cardiovascular disease or chronic kidney disease. The 2020 switching review also noted liraglutide was, at that time, the only GLP-1 receptor agonist indicated for children 10 and older with type 2 diabetes.
Does oral semaglutide work as well as the injection?
Against injected liraglutide, yes on blood sugar: PIONEER 4 found oral semaglutide 14 mg noninferior, -1.2 versus -1.1 A1C points, and better on weight, -4.4 versus -3.1 kg.
This article summarizes FDA labeling, published research and company information current as of September 14, 2026. It is not medical advice and does not replace a conversation with your own healthcare provider. How we research and verify.