Trulicity vs Ozempic: What the Head-to-Head Trial Actually Showed

Most drug comparisons you find online are guesswork. Two medicines get tested against a placebo in separate studies, someone lines the numbers up in a table, and you are left comparing populations that were never comparable.

Trulicity and Ozempic are different. They were put head to head in a real randomized trial, with the same patients, the same background medication and the same 40-week clock. That makes this one of the few GLP-1 comparisons where you can give a straight answer.

This article walks through what that trial found, and then through the things a trial cannot tell you: how the pens differ, what each one costs, what their heart indications actually say, and what is changing in 2026.

None of this is medical advice. It describes what the labels, the trials and the pricing data say. Which medicine belongs in your life is a conversation with a healthcare provider.

What are Trulicity and Ozempic?

Both are GLP-1 receptor agonists — medicines that mimic a gut hormone your body releases after you eat. They prompt the pancreas to release insulin when blood sugar is high, reduce the glucagon that raises blood sugar, slow how fast the stomach empties, and reduce appetite.

Trulicity is dulaglutide, made by Eli Lilly. It was approved in the US in 2014 and is injected once a week. Its label covers two things: improving blood sugar in adults and children 10 and older with type 2 diabetes, and reducing the risk of major adverse cardiovascular events in adults with type 2 diabetes who have established cardiovascular disease or multiple cardiovascular risk factors [1].

Ozempic is semaglutide, made by Novo Nordisk, approved in 2017 and also injected once a week. Since May 2026 there is also an Ozempic pill — a daily tablet that replaced the brand formerly sold as Rybelsus [2].

Neither Trulicity nor Ozempic is approved for weight loss in the United States. The semaglutide product approved for weight management is Wegovy. There is no Trulicity equivalent; Lilly’s weight-management drug is Zepbound, which contains tirzepatide, a different molecule.

Both carry a boxed warning about thyroid C-cell tumors, based on rodent studies, and both are contraindicated in people with a personal or family history of medullary thyroid carcinoma or MEN 2 [1].

What did the head-to-head trial show?

The trial was called SUSTAIN 7. Novo Nordisk ran it at 194 sites in 16 countries and published it in The Lancet Diabetes & Endocrinology in 2018 [3].

1,201 adults with type 2 diabetes that was not well controlled on metformin alone were randomly assigned to one of four weekly injections for 40 weeks: semaglutide 0.5 mg, dulaglutide 0.75 mg, semaglutide 1.0 mg, or dulaglutide 1.5 mg. The pairings were deliberate — low dose against low dose, high dose against high dose.

Blood sugar. From a starting A1C of about 8.2 percent:

• Semaglutide 0.5 mg lowered A1C by 1.5 percentage points; dulaglutide 0.75 mg by 1.1. Difference: 0.40 points in favor of semaglutide.
• Semaglutide 1.0 mg lowered A1C by 1.8 points; dulaglutide 1.5 mg by 1.4. Difference: 0.41 points in favor of semaglutide.

Both comparisons were statistically significant [3].

Body weight. From a mean starting weight of about 95 kg:

• Semaglutide 0.5 mg: 4.6 kg lost. Dulaglutide 0.75 mg: 2.3 kg. Difference: 2.26 kg.
• Semaglutide 1.0 mg: 6.5 kg lost. Dulaglutide 1.5 mg: 3.0 kg. Difference: 3.55 kg.

At the higher doses, semaglutide produced roughly twice the weight loss [3].

Side effects. Gastrointestinal problems were the most common issue in every group and the most common reason people stopped. Rates were broadly similar: 43 percent on semaglutide 0.5 mg, 44 percent on semaglutide 1.0 mg, 33 percent on dulaglutide 0.75 mg and 48 percent on dulaglutide 1.5 mg [3].

So on the two numbers most people care about, semaglutide won — without being noticeably harder to tolerate.

The honest caveats

SUSTAIN 7 randomized patients in 2016. Since then:

• Trulicity gained two higher doses, 3 mg and 4.5 mg, which were not in the trial.
• Ozempic gained a 2 mg dose, which was also not in the trial.
• Novo Nordisk funded and ran the study. That does not invalidate it — it was randomized, published in a major journal, and its results have been reproduced in subgroup analyses — but it is worth knowing.

The higher Trulicity doses close some of the gap, but not all of it. In Lilly’s own AWARD-11 trial, 1,842 patients on metformin were randomized to dulaglutide 1.5, 3.0 or 4.5 mg. At 36 weeks the 4.5 mg dose lowered A1C by 1.77 percentage points versus 1.54 with 1.5 mg, and produced 4.6 kg of weight loss versus 3.0 kg. That is about a quarter of an A1C point and about 1.6 extra kilograms for triple the dose [4].

How do the doses work?

Both medicines start low and step up, because gastrointestinal side effects track dose escalation.

Trulicity. Its label describes the following ladder [1]:

• Adults begin at 0.75 mg once weekly.
• After 4 weeks, the dosage may be increased to 1.5 mg for additional glycemic control.
• If more is needed, the label allows increases in 1.5 mg increments after at least 4 weeks at the current dosage.
• The maximum recommended dosage is 4.5 mg once weekly.
• For children 10 and older, the starting dosage is 0.75 mg and the maximum is 1.5 mg.

That is a summary of the FDA-approved prescribing information and the Instructions for Use, provided for context rather than as directions. Your own prescription, and the schedule your prescriber sets, is what governs your dosing.

Trulicity comes in four strengths, each in its own single-dose pen: 0.75, 1.5, 3 and 4.5 mg, all in 0.5 mL.

Ozempic uses a different ladder, starting at 0.25 mg for four weeks as a tolerance-building dose that is not intended to control blood sugar on its own, then moving through 0.5, 1 and 2 mg.

Both are injected any time of day, with or without food, into the abdomen, thigh or upper arm, rotating sites [1].

A note on dose numbers: the milligram figures are not comparable between the two drugs. Semaglutide 1 mg and dulaglutide 1.5 mg are different molecules at different molecular weights. Comparing the numbers directly tells you nothing useful.

Which one is better for weight?

In the trial data, semaglutide. But the framing matters, because neither drug is approved for this purpose.

In SUSTAIN 7, at the highest doses tested, participants lost about 6.5 kg on semaglutide and about 3.0 kg on dulaglutide over 40 weeks [3]. In AWARD-11, the top Trulicity dose produced about 4.6 kg over 36 weeks [4]. These are people with type 2 diabetes taking a diabetes medication, and the weight loss was measured as a secondary endpoint.

For comparison, the drugs actually approved for weight management reach very different numbers. In the STEP 1 trial, semaglutide 2.4 mg — the Wegovy dose — produced a 14.9 percent mean weight reduction over 68 weeks [5]. In SURMOUNT-1, tirzepatide 15 mg produced a 20.9 percent reduction over 72 weeks [6].

If weight is the goal, the honest answer is that neither Trulicity nor Ozempic is the drug designed for it. That conversation belongs with a healthcare provider who can look at your diagnoses, your coverage and your history.

What about the heart?

Both drugs have cardiovascular language on their labels, but they earned it in different trials.

Trulicity’s evidence is REWIND, published in The Lancet in 2019 [7]. It enrolled 9,901 people aged 50 and older with type 2 diabetes and followed them for a median of 5.4 years — the longest GLP-1 cardiovascular outcomes trial run to date. What made REWIND unusual is that only 31.5 percent of participants had established cardiovascular disease at the start. Most were there on risk factors alone.

The results: the combined outcome of nonfatal heart attack, nonfatal stroke or cardiovascular death occurred in 12.0 percent of people on dulaglutide versus 13.4 percent on placebo, a hazard ratio of 0.88. Breaking it apart, the benefit came almost entirely from stroke: a 24 percent reduction in nonfatal stroke. There was no discernible effect on nonfatal heart attack and a neutral effect on cardiovascular death, and all-cause mortality did not differ significantly between groups [7].

Gastrointestinal side effects were common over those years: 47.4 percent of the dulaglutide group reported one, against 34.1 percent on placebo [7].

Ozempic’s cardiovascular indication rests on a different trial in a different population. Practically, this means the two labels are not interchangeable claims. If a prescriber is choosing a GLP-1 specifically for cardiovascular protection, the trial population that most resembles the patient in front of them is part of the decision.

What do they cost?

Here the two are much closer than their trial results.

Eli Lilly publishes a list price of $1,006.93 per month for Trulicity, defined as four pens, based on wholesale acquisition cost as of January 1, 2026 [8].

A more neutral comparison is the National Average Drug Acquisition Cost, or NADAC — a survey-based figure for what US retail pharmacies actually pay. It is not a patient price and it ignores rebates, but it lets you compare brands on the same basis [9]:

Product	NADAC per mL or tablet	Estimated monthly acquisition cost
Trulicity 4.5 mg pen	$487.38 per mL (Aug 19, 2026)	about $975 for four 0.5 mL pens
Ozempic pen	about $332 per mL (Aug 19, 2026)	about $996 for one 3 mL pen
Ozempic tablets (1.5 mg)	$33.12 per tablet (Aug 19, 2026)	about $994 for 30 tablets
Generic liraglutide, 3-pack	$32.00 per mL (Aug 19, 2026)	about $288

Monthly figures are estimates calculated from the per-unit price and typical dosing.

Two things stand out. First, Trulicity and Ozempic land within about 2 percent of each other, so cost almost never decides between them. Second, both sit roughly three times above generic liraglutide, which is why many insurance plans now route people to the generic first. That is a formulary decision, not a clinical one, and it is worth understanding before you assume a denial is about your health.

One change is already scheduled. On February 24, 2026 Novo Nordisk announced it would cut the US list price of Ozempic, Wegovy and Rybelsus to $675 per month effective January 1, 2027 — the same date the Medicare negotiated price of $274 per month for semaglutide takes effect [14][15]. Lilly has announced no equivalent change for Trulicity, so the two products’ list prices are likely to diverge in 2027.

What you actually pay is a different question entirely. Lilly says about 40 percent of patients with employer or private coverage pay $0 per Trulicity prescription and 90 percent pay under $75, and about 70 percent of Medicare patients pay $0 [8]. Its savings card offers eligible commercially insured patients with Trulicity coverage as little as $25 for up to a three-month prescription [10]. Terms and eligibility rules apply, and government-insured patients are generally excluded from manufacturer copay cards.

Is anything changing in 2026?

Yes, on both sides.

Trulicity and Medicare. On January 27, 2026, CMS named Trulicity among 15 drugs selected for the third cycle of the Medicare Drug Price Negotiation Program. Manufacturers had until February 28, 2026 to decide whether to take part, and on March 13, 2026 CMS confirmed that all 15, Lilly included, had chosen to participate. Negotiations run through 2026 and any negotiated maximum fair price takes effect January 1, 2028 [11]. Trulicity is the second GLP-1 franchise selected; Novo Nordisk’s semaglutide products were chosen for 2027, at a negotiated price of $274 per month [15]. This does not affect availability, but it will affect what Medicare pays.

Ozempic in a pill. Novo Nordisk retired the Rybelsus brand in the US in 2026 and moved oral semaglutide under the Ozempic name. Ozempic tablets in 1.5, 4 and 9 mg strengths reached pharmacies on May 4, 2026 [2]. If you were on Rybelsus, this matters: the label states the two tablet formulations are not substitutable on a milligram-for-milligram basis, and Novo says current Rybelsus patients need a new prescription with the new strength and NDC.

Trulicity is not going away. Despite what some outdated pages claim, Trulicity was still actively listed by the FDA in September 2026 with product listings running into 2027 and no open shortage record. It is a declining franchise — Lilly no longer breaks it out as a key product, and its patients have been migrating to tirzepatide for years — but declining is not the same as discontinued.

How do people actually choose between them?

In practice, the decision usually comes down to four things, and only one of them is efficacy.

Coverage. Most commercial plans require a trial of metformin at the maximum tolerated dose before covering any GLP-1 for type 2 diabetes, then designate a short list of preferred agents. UnitedHealthcare’s December 2024 provider notice, for example, listed Mounjaro, Ozempic, Rybelsus, Trulicity and liraglutide as preferred on commercial plans, and a shorter list on its marketplace plans [12]. Your plan’s list, not the trial data, often determines which one you start.

The device. Trulicity’s single-dose pen hides the needle and requires no assembly. Ozempic’s pen holds multiple doses and needs a needle attached each time. For someone with needle anxiety or limited dexterity, this is not a small detail.

Tolerability. Nausea, vomiting and diarrhea are the most common reasons people stop either drug. Some people tolerate one and not the other. That is one of the documented reasons clinicians switch patients between GLP-1s [13].

What else you are treating. Kidney disease, heart failure, established cardiovascular disease and a genuine need for weight reduction all push the decision in different directions, and the ADA’s 2026 Standards of Care specify that a GLP-1 receptor agonist with demonstrated benefit is preferred for glycemic management in the right patients.

What should you do with this?

If you are already on one of these and it is working, the trial data is not a reason to change. A 0.4 percentage point A1C difference in a 40-week trial does not mean your current medicine has failed you.

If you are not getting the results you want, or the side effects are not settling, or your coverage has changed, that is a conversation to have — and it is worth bringing specifics: your A1C trend, your weight trend, what side effects you are having and when, and what your plan actually covers.

Two points from the source documents are worth carrying into that conversation. First, every dose in this article is a summary of the FDA-approved prescribing information and Instructions for Use; the schedule that applies to you is the one on your own prescription. Second, the published switching guidance states that two GLP-1 receptor agonists should not be taken together, and the fixed-ratio combination labels require the prior GLP-1 to be discontinued before the new product is started [13].

Sources

1. TRULICITY (dulaglutide) injection — US prescribing information, US Food and Drug Administration
2. Novo Nordisk’s Ozempic pill soon to be available in the US, Novo Nordisk, May 1, 2026
3. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7), The Lancet Diabetes & Endocrinology, 2018
4. Efficacy and Safety of Dulaglutide 3.0 mg and 4.5 mg Versus Dulaglutide 1.5 mg (AWARD-11), Diabetes Care, 2021
5. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1), New England Journal of Medicine, 2021
6. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1), New England Journal of Medicine, 2022
7. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND), The Lancet, 2019
8. How much should I expect to pay for Trulicity?, Eli Lilly and Company
9. NADAC (National Average Drug Acquisition Cost) 2026, Centers for Medicare & Medicaid Services
10. Trulicity Savings Card, Cost and Resources, Eli Lilly and Company
11. CMS Announces Selection of Drugs for Third Cycle of Medicare Drug Price Negotiation Program, CMS, January 27, 2026
12. Discontinuation of Bydureon BCise and Byetta, UnitedHealthcare, December 19, 2024
13. Switching Between Glucagon-Like Peptide-1 Receptor Agonists: Rationale and Practical Guidance, Clinical Diabetes, 2020
14. Novo Nordisk’s GLP-1 list price cut: what to watch next, Mercer, 2026 (reporting Novo Nordisk’s February 24, 2026 announcement)
15. Medicare Drug Price Negotiation Program: selected drugs and negotiated prices, Centers for Medicare & Medicaid Services