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Research · Medication

Dulaglutide

Trials found weekly dulaglutide lowered HbA1c by about 1.2 points against almost no change on placebo, and in REWIND it cut heart attacks, strokes and cardiovascular deaths by 12% in people with type 2 diabetes. Weight loss was small, about 1 kg against placebo. Nausea, vomiting and diarrhea were very common. Semaglutide lowered HbA1c and weight more head to head.

Add to Bio HackChecked 2026-11-13
Status
Prescription drug in the US. FDA-approved as a weekly injection, with diet and exercise, to improve blood sugar control in adults and children 10 and older with type 2 diabetes, and to reduce the risk of major cardiovascular events in adults with type 2 diabetes who have heart disease or several cardiovascular risk factors. It is not approved for weight loss. The label carries a boxed warning for thyroid C-cell tumors seen in rats.
Also called
dulaglutide, Trulicity, GLP-1, GLP-1 receptor agonist, once-weekly GLP-1
Taken for
type 2 diabetes, blood sugar, A1c, heart attack and stroke prevention, weight loss, kidney protection

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help6

Reported risks11

What people take it for, and what was found

Shown to help6

ModerateVery common

Blood sugar control in type 2 diabetes

Shown to lower HbA1c by about 1.0 to 1.2 points against almost no change on placebo in adults with type 2 diabetes, with 62% reaching under 7% against 22%.

Compared with placebo [1]; sitagliptin, metformin, exenatide and insulin glargine [1]; other diabetes drugs in a network meta-analysis [2]

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Added to metformin, HbA1c changed by -1.0 points on 0.75 mg, -1.2 on 1.5 mg, -0.6 on sitagliptin and +0.1 on placebo at 26 weeks. HbA1c under 7% was reached by 56%, 62%, 39% and 22%, and fasting glucose fell 35, 41, 18 and 9 mg/dL. In other placebo-controlled trials, dulaglutide lowered HbA1c more than placebo when added to glimepiride, to metformin with pioglitazone, and to SGLT2 inhibitors [1]. A network meta-analysis of 453 trials found that specific GLP-1 receptor agonists added to metformin, with insulin regimens, produced the largest HbA1c reductions [2].
Population
972 adults on metformin in one trial and other placebo-controlled trials described in the label [1]; 453 trials of 21 glucose-lowering treatments [2].
Sources
[1], [2]
Caveats
The trials were funded by the manufacturer. The network meta-analysis abstract does not give a dulaglutide estimate [2].
Limited

Higher doses of 3 mg and 4.5 mg

One trial found 4.5 mg lowered HbA1c 0.24 points more and weight 1.6 kg more than 1.5 mg over 36 weeks, with more nausea and vomiting.

Compared with dulaglutide 1.5 mg [3]

The numbers and sources
Effect
At 36 weeks, HbA1c fell 1.77 points on 4.5 mg and 1.54 on 1.5 mg (difference -0.24, P under 0.001). The 3 mg dose beat 1.5 mg only in the on-treatment analysis (-0.17 points). Weight fell 4.6 kg on 4.5 mg and 3.0 kg on 1.5 mg. Nausea occurred in 13.4%, 15.6% and 16.4%, and vomiting in 5.6%, 8.3% and 9.3%, on 1.5, 3 and 4.5 mg [3].
Population
1,842 adults with type 2 diabetes on metformin, mean HbA1c 8.6% and BMI 34.2, over 52 weeks [3].
Sources
[3]
Caveats
One trial with no placebo arm, funded by the manufacturer.
Why limited
This rests on one trial, of 1,842 people. Strength counts independent studies that agree, so one trial is limited at any size.
LimitedStudied in children

Blood sugar in children and teenagers with type 2 diabetes

One trial in youths with type 2 diabetes found dulaglutide lowered HbA1c by 0.9 points while it rose 0.6 on placebo, with no difference in BMI.

Compared with placebo [5]

The numbers and sources
Effect
At 26 weeks, HbA1c rose 0.6 points on placebo and fell 0.6 on 0.75 mg and 0.9 on 1.5 mg. HbA1c under 7% was reached by 51% on dulaglutide against 14% on placebo. Fasting glucose rose 17.1 mg/dL on placebo and fell 18.9 mg/dL on dulaglutide. BMI change did not differ [5].
Population
154 youths aged 10 to under 18 with type 2 diabetes, on lifestyle changes alone or with metformin, with or without basal insulin [5].
Sources
[5]
Caveats
One small trial, funded by the manufacturer. Gastrointestinal adverse events were more frequent than on placebo [5].
Limited

Heart attack, stroke and cardiovascular death

One large trial found major cardiovascular events in 12.0% on dulaglutide against 13.4% on placebo over 5.4 years in adults with type 2 diabetes.

Compared with placebo [6]; other glucose-lowering drugs in a network meta-analysis [2]

The numbers and sources
Effect
Non-fatal heart attack, non-fatal stroke or cardiovascular death occurred in 12.0% on dulaglutide and 13.4% on placebo, 2.4 against 2.7 per 100 person-years (HR 0.88, 95% CI 0.79 to 0.99). Death from any cause did not differ (HR 0.90, 95% CI 0.80 to 1.01) [6]. In a network meta-analysis of people at increased cardiovascular risk on metformin-based treatment, the odds of stroke were lower with dulaglutide [2].
Population
9,901 adults aged 50 or older with type 2 diabetes and previous cardiovascular disease or risk factors, median HbA1c 7.2%, 46.3% women [6]; 21 trials in people at increased cardiovascular risk [2].
Sources
[6], [2]
Caveats
One trial, funded by the manufacturer. The absolute difference was 1.4 percentage points over a median 5.4 years [6].
Why limited
This rests on one trial, of 9,901 people. Strength counts independent studies that agree, so one trial is limited at any size.
Limited

Kidney outcomes in type 2 diabetes

One large trial found a 15% lower rate of a combined kidney outcome on dulaglutide, mostly from less new heavy protein in the urine.

Compared with placebo [7]

The numbers and sources
Effect
The kidney outcome, new macroalbuminuria, a sustained 30% or greater fall in eGFR, or chronic kidney replacement, occurred in 17.1% on dulaglutide and 19.6% on placebo (HR 0.85, 95% CI 0.77 to 0.93). New macroalbuminuria fell (HR 0.77, 95% CI 0.68 to 0.87), while the eGFR decline (HR 0.89, 95% CI 0.78 to 1.01) and kidney replacement therapy (HR 0.75, 95% CI 0.39 to 1.44) did not differ significantly [7].
Population
9,901 adults with type 2 diabetes in REWIND, mean eGFR 76.9, followed a median 5.4 years [7].
Sources
[7]
Caveats
An exploratory analysis of a cardiovascular trial, funded by the manufacturer [7].
Why limited
This rests on one trial, of 9,901 people. Strength counts independent studies that agree, so one trial is limited at any size.
Moderate

Weight loss

Shown to lower weight modestly in type 2 diabetes, about 0.9 kg more than placebo overall and 1.9 kg at doses above 1 mg, in a meta-analysis of 18 trials.

Compared with placebo [8]; dulaglutide 1.5 mg [3]; semaglutide [4]

The numbers and sources
Effect
Dulaglutide lowered body weight against placebo (WMD -0.86 kg, 95% CI -1.22 to -0.49), BMI (WMD -0.68 kg/m2) and waist circumference (WMD -1.23 cm). At doses above 1 mg, weight fell 1.94 kg more (95% CI -2.54 to -1.34), and in trials over 18 weeks 1.42 kg more [8]. At 4.5 mg, weight fell 4.6 kg against 3.0 kg on 1.5 mg [3]. Semaglutide 1.0 mg lowered weight 3.55 kg more than dulaglutide 1.5 mg [4].
Population
14,612 adults with type 2 diabetes in 18 trials with 33 arms [8]; 1,842 adults [3]; 1,201 adults [4].
Sources
[8], [3], [4]
Caveats
Dulaglutide is not approved for weight loss, and no trial in people without diabetes was located.

Not shown to help1

Limited

Compared with semaglutide

One head-to-head trial found semaglutide lowered HbA1c about 0.4 points more and weight 2.3 to 3.6 kg more than dulaglutide at matched dose levels over 40 weeks.

Compared with semaglutide [4]

The numbers and sources
Effect
HbA1c fell 1.4 points on dulaglutide 1.5 mg and 1.8 on semaglutide 1.0 mg (difference -0.41), and 1.1 on dulaglutide 0.75 mg against 1.5 on semaglutide 0.5 mg (difference -0.40). Weight fell 3.0 kg against 6.5 kg (difference -3.55 kg) and 2.3 kg against 4.6 kg. Gastrointestinal disorders occurred in 48% on dulaglutide 1.5 mg and 44% on semaglutide 1.0 mg [4].
Population
1,201 adults with type 2 diabetes on metformin in 16 countries [4].
Sources
[4]
Caveats
Open label, funded by the maker of semaglutide. Dulaglutide still lowered HbA1c and weight from baseline in both arms [4].
Why limited
This rests on one trial, of 1,201 people. Strength counts independent studies that agree, so one trial is limited at any size.

Doses studied

The label starts at 0.75 mg injected once a week, with a step to 1.5 mg after 4 weeks and further 1.5 mg steps every 4 weeks to a maximum of 4.5 mg. The maximum for children is 1.5 mg [1]. REWIND used 1.5 mg weekly [6]. AWARD-11 compared 1.5, 3 and 4.5 mg [3], and SUSTAIN 7 used 0.75 and 1.5 mg against semaglutide 0.5 and 1.0 mg [4]. The youth trial used 0.75 and 1.5 mg [5].

Risks

Reported risks10

ModerateVery common

Nausea, vomiting and diarrhea

Shown to raise stomach side effects, with nausea in 21% on 1.5 mg against 5% on placebo and vomiting in 13% against 2%.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In pooled placebo-controlled trials, nausea occurred in 21.1% on 1.5 mg, 12.4% on 0.75 mg and 5.3% on placebo, vomiting in 12.7%, 6.0% and 2.3%, diarrhea in 12.6%, 8.9% and 6.7%, abdominal pain in 9.4%, 6.5% and 4.9%, and decreased appetite in 8.6%, 4.9% and 1.6%. Any gastrointestinal reaction occurred in 41%, 32% and 21%, and 3.5%, 1.3% and 0.2% stopped because of one. Severe gastrointestinal reactions occurred in 4.3%, 2.2% and 1.4% [1]. In REWIND, 47.4% on dulaglutide and 34.1% on placebo reported a gastrointestinal adverse event [6].
Population
1,670 adults on dulaglutide and 568 on placebo, mean exposure 23.8 weeks [1]; 9,901 adults [6].
Sources
[1], [6]
Caveats
The label advises against use in people with severe gastroparesis [1].
ModerateVery common

Low blood sugar with insulin or sulfonylureas

Shown to raise low blood sugar when combined with insulin or a sulfonylurea, in 14.7% against 9.3% on placebo with insulin glargine, and rarely without them.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
With insulin glargine, glucose below 54 mg/dL occurred in 14.7% on dulaglutide and 9.3% on placebo, and severe hypoglycemia in 0.7% against 0%. With glimepiride, it occurred in 3.3% against 0%. With metformin alone it occurred in 0.3% to 0.7%. With a sulfonylurea over 78 weeks it occurred in 20% to 21%, and with mealtime insulin over 52 weeks in 69% to 77% [1].
Population
Adults with type 2 diabetes in the trials described in the label [1].
Sources
[1]
Caveats
The higher rates came from trials without a placebo arm [1].
ModerateCommon

Faster heart rate and heart conduction changes

Shown to raise heart rate by 2 to 4 beats a minute, with sinus tachycardia in 5.6% on 1.5 mg against 3.0% on placebo.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
Dulaglutide raised mean heart rate by 2 to 4 beats a minute. Sinus tachycardia was reported in 5.6% on 1.5 mg, 2.8% on 0.75 mg and 3.0% on placebo, persisting in 1.6%, 0.4% and 0.2%. The PR interval rose 2 to 3 milliseconds against a 0.9 millisecond fall on placebo [1].
Population
Adults in placebo-controlled trials described in the label [1].
Sources
[1]
Caveats
Pooled trial data from the manufacturer, without confidence intervals.
LimitedCommon

Diabetic eye disease complications

One large trial found diabetic retinopathy complications in 1.9% on dulaglutide against 1.5% on placebo, and 8.5% against 6.2% in people with prior retinopathy.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
Over a median 5.4 years, diabetic retinopathy complications occurred in 1.9% on dulaglutide 1.5 mg and 1.5% on placebo. In people with retinopathy at baseline the rates were 8.5% and 6.2%, and without it 1% in each group. The label notes that rapid improvement in glucose control has been linked to temporary worsening of retinopathy [1].
Population
9,901 adults in REWIND, as reported in the label [1].
Sources
[1]
Caveats
A secondary outcome, reported without a confidence interval.
Why limited
This rests on one trial, of 9,901 people. Strength counts independent studies that agree, so one trial is limited at any size.
ModerateUncommon

Gallbladder disease

Shown to raise gallbladder and bile duct disease about 37% across GLP-1 drug trials. In REWIND, serious acute cholecystitis occurred in 0.5% on dulaglutide against 0.3%.

The numbers and sources
How common
Uncommon: between 1 in 1,000 and 1 in 100 people.
Effect
In REWIND, gallstones occurred at 0.62 per 100 patient-years on dulaglutide and 0.56 on placebo, and serious acute cholecystitis in 0.5% against 0.3% [1]. Across GLP-1 receptor agonist trials, the relative risk of gallbladder or biliary disease was 1.37 (95% CI 1.23 to 1.52), higher at higher doses and with longer use [11].
Population
9,901 adults in REWIND, as reported in the label [1]; 103,371 patients in 76 trials [11].
Sources
[1], [11]
Caveats
The meta-analysis pools all GLP-1 receptor agonists [11].
LimitedUncommon

Allergic and injection site reactions

The label reports systemic allergic reactions in 0.5% of adults in trials and injection site reactions in 0.5% against 0% on placebo, with postmarketing anaphylaxis.

The numbers and sources
How common
Uncommon: between 1 in 1,000 and 1 in 100 people.
Effect
Systemic hypersensitivity reactions, such as severe hives, widespread rash and facial or lip swelling, occurred in 0.5% of adults on dulaglutide. Injection site reactions occurred in 0.5% against 0.0% on placebo. Anaphylaxis and angioedema have been reported after marketing [1].
Population
Adults in clinical trials and postmarketing reports [1].
Sources
[1]
Caveats
No placebo rate is given for systemic reactions.
LimitedHow often is not known

Pancreatitis

The label reports pancreatitis at 3.4 per 1,000 patient-years on dulaglutide against 2.7 on other drugs, and pancreatic enzyme rises of 14% to 20%.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
In the registration trials, pancreatitis-related reactions occurred at 3.4 per 1,000 patient-years on dulaglutide and 2.7 on non-incretin comparators, and adjudicated pancreatitis at 1.4 and 0.88. Lipase and pancreatic amylase rose 14% to 20% from baseline, against up to 3% on placebo. Fatal and non-fatal hemorrhagic or necrotizing pancreatitis has been observed with GLP-1 receptor agonists [1].
Population
Adults in the registration trials [1].
Sources
[1]
Caveats
Few events, given per patient-year rather than per person.
LimitedHow often is not known

Kidney injury from dehydration

The label reports acute kidney injury, some needing dialysis, mostly in people dehydrated by nausea, vomiting or diarrhea. It gives no rate.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Postmarketing reports describe acute kidney injury, in some cases needing hemodialysis, in people on GLP-1 receptor agonists including dulaglutide, most after gastrointestinal reactions led to dehydration [1].
Population
Postmarketing reports [1].
Sources
[1]
Caveats
Reports, with no denominator.
LimitedHow often is not known

Inhaling stomach contents under anesthesia

The label reports rare cases of pulmonary aspiration during anesthesia or deep sedation in people on GLP-1 drugs, with food still in the stomach despite fasting.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Dulaglutide delays gastric emptying. Rare postmarketing reports describe pulmonary aspiration during elective procedures under general anesthesia or deep sedation in people on GLP-1 receptor agonists who had retained stomach contents despite following fasting instructions [1].
Population
Postmarketing reports [1].
Sources
[1]
Caveats
The label states the data are insufficient to say whether changing fasting or pausing the drug would reduce the risk [1].
LimitedHow often is not known

Medicines taken by mouth

The label states dulaglutide slows stomach emptying and may slow absorption of oral medicines, though 1.5 mg did not change tested drugs to a clinically relevant degree.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The delay in gastric emptying is largest after the first dose and lessens over time. In pharmacology studies, 1.5 mg did not affect absorption of the tested oral medicines to a clinically relevant degree. The label advises monitoring levels of oral drugs with a narrow therapeutic index, such as warfarin, and notes limited experience at 3 and 4.5 mg [1].
Population
Clinical pharmacology studies described in the label [1].
Sources
[1]
Caveats
No rate of harm is given.

Mixed results1

LimitedHow often is not known

FDA boxed warning: thyroid C-cell tumors

FDA states dulaglutide caused thyroid C-cell tumors in rats and the human relevance is unknown. Two large GLP-1 drug studies in people disagreed on thyroid cancer risk.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The boxed warning states dulaglutide caused dose- and duration-dependent thyroid C-cell tumors in rats, and that it is unknown whether it causes them in humans. It is contraindicated with a personal or family history of medullary thyroid cancer or MEN 2. One case of medullary thyroid cancer occurred in a trial patient with calcitonin about 8 times the upper limit before treatment, and one case of C-cell hyperplasia in REWIND [1]. In French data, GLP-1 receptor agonist use for 1 to 3 years was linked to thyroid cancer (HR 1.58, 95% CI 1.27 to 1.95) and medullary thyroid cancer (HR 1.78, 95% CI 1.04 to 3.05) [9]. In Scandinavian registries, GLP-1 receptor agonists were not linked to thyroid cancer against DPP-4 inhibitors (HR 0.93, 95% CI 0.66 to 1.31) [10].
Population
Rats, and trial participants [1]; 2,562 thyroid cancer cases and 45,184 matched controls with type 2 diabetes [9]; 145,410 GLP-1 receptor agonist users and 291,667 DPP-4 inhibitor users [10].
Sources
[1], [9], [10]
Caveats
Both human studies pool all GLP-1 receptor agonists and are observational [9][10].

Possible, not studied in people1

Untested

Pregnancy

Not studied in people. Animal studies found fetal losses, slower fetal growth and malformations at doses above human exposure, alongside reduced maternal eating.

No study in people. This rests on animal studies.

The numbers and sources
Effect
The label states human data are not sufficient to determine a drug-associated risk. In rats, early embryonic deaths, reduced fetal growth and abnormalities occurred at 6 or more times human exposure at 4.5 mg, and in rabbits major fetal abnormalities at 5 times, with reduced maternal food intake and weight [1].
Population
Pregnant rats and rabbits (animal), as reported in the label [1].
Sources
[1]
Caveats
Animal findings at exposures above the human dose, linked to reduced maternal eating [1].

Claims tested and not found

  1. That dulaglutide lowers death from any cause. In REWIND, deaths occurred in 10.8% on dulaglutide and 12.0% on placebo (HR 0.90, 95% CI 0.80 to 1.01), not a significant difference [6].
  2. That dulaglutide lowers BMI in youths with type 2 diabetes. In a 26-week trial in 154 youths, BMI change did not differ from placebo [5].

Related

SemaglutideLiraglutideTirzepatideMetforminSGLT2 inhibitors

Sources

  1. U.S. Food and Drug Administration. TRULICITY (dulaglutide) injection, prescribing information. 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=463050bd-2b1c-40f5-b3c3-0a04bb433309
  2. Tsapas A, Avgerinos I, Karagiannis T, et al. Comparative Effectiveness of Glucose-Lowering Drugs for Type 2 Diabetes: A Systematic Review and Network Meta-analysis. Annals of Internal Medicine. 2020. https://doi.org/10.7326/M20-0864
  3. Frias JP, Bonora E, Nevarez Ruiz L, et al. 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). Diabetes Care. 2021. https://doi.org/10.2337/dc20-1473
  4. Pratley RE, Aroda VR, Lingvay I, et al. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. The Lancet Diabetes & Endocrinology. 2018. https://doi.org/10.1016/S2213-8587(18)30024-X
  5. Arslanian SA, Hannon T, Zeitler P, et al. Once-Weekly Dulaglutide for the Treatment of Youths with Type 2 Diabetes. New England Journal of Medicine. 2022. https://doi.org/10.1056/NEJMoa2204601
  6. Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. The Lancet. 2019. https://doi.org/10.1016/S0140-6736(19)31149-3
  7. Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial. The Lancet. 2019. https://doi.org/10.1016/S0140-6736(19)31150-X
  8. Li Y, Gong X, Găman MA, et al. The effect of subcutaneous dulaglutide on weight loss in patients with Type 2 diabetes mellitus: Systematic review and meta-analysis of randomized controlled trials. European Journal of Clinical Investigation. 2024. https://doi.org/10.1111/eci.14125
  9. Bezin J, Gouverneur A, Pénichon M, et al. GLP-1 Receptor Agonists and the Risk of Thyroid Cancer. Diabetes Care. 2023. https://doi.org/10.2337/dc22-1148
  10. Pasternak B, Wintzell V, Hviid A, et al. Glucagon-like peptide 1 receptor agonist use and risk of thyroid cancer: Scandinavian cohort study. BMJ. 2024. https://doi.org/10.1136/bmj-2023-078225
  11. He L, Wang J, Ping F, et al. Association of Glucagon-Like Peptide-1 Receptor Agonist Use With Risk of Gallbladder and Biliary Diseases: A Systematic Review and Meta-analysis of Randomized Clinical Trials. JAMA Internal Medicine. 2022. https://doi.org/10.1001/jamainternmed.2022.0338

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