Search Retatrutide - Diabetes (type in keywords)

Search Medical Information

If you wish to report an adverse event or product complaint, please call 1-800-LILLYRX (1-800-545-5979)

Retatrutide-Diabetes

This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling.

How did retatrutide compare with semaglutide 2 mg in adults with type 2 diabetes in TRANSCEND-T2D-2?

In TRANSCEND-T2D-2, retatrutide met the primary and key secondary endpoints at week 80. Retatrutide 9 mg and 12 mg vs semaglutide 2 mg reduced HbA1c by -2.2% (both doses) vs -1.8% and body weight by -19.5% (9 mg) and -20.9% (12 mg) vs -9.4%, respectively.

US_cFAQ_RETA002A_vs_SEMA_TRANSCEND-T2D-2_T2D_v0_4_for_HTML

Content Overview

What is retatrutide?
What is the design of TRANSCEND-T2D-2?
- Rationale for the Semaglutide 2 mg Comparator
- TRANSCEND-T2D-2 Inclusion and Exclusion Criteria
What are the preliminary efficacy outcomes of TRANSCEND-T2D-2?
What are the preliminary safety outcomes of TRANSCEND-T2D-2?
What are the future expectations for retatrutide?
References

What is retatrutide?

Retatrutide is an investigational, once-weekly, triple–hormone-receptor agonist that activates the

glucose-dependent insulinotropic polypeptide (GIP) receptor
glucagon-like peptide-1 (GLP-1) receptor, and
glucagon receptor.¹^,2

Eli Lilly and Company is studying retatrutide in the TRANSCEND-T2D phase 3 clinical program to evaluate its potential efficacy and safety in adults with type 2 diabetes.¹

Retatrutide has not been approved by the US Food and Drug Administration or by any regulatory authority anywhere in the world, and it cannot be legally sold or marketed for human use.¹

Back to Content Overview

What is the design of TRANSCEND-T2D-2?

TRANSCEND-T2D-2 (NCT06260722) is an 80-week phase 3, randomized, open-label, parallel-group trial comparing retatrutide 9 mg and 12 mg with semaglutide 2 mg in 1298 adults with type 2 diabetes inadequately controlled with metformin, with or without a sodium-glucose cotransporter-2 inhibitor.¹^,³ The trial was conducted at 77 sites in Argentina, Canada, Mexico, Puerto Rico, and the United States.³

Figure 1. TRANSCEND-T2D-2 Trial Design^1,3

Trial design schematic for TRANSCEND-T2D-2: 2:2:1 randomization to retatrutide 9 mg, retatrutide 12 mg, or semaglutide 2 mg over 80 weeks.

Figure 1 description: Adults with type 2 diabetes and a glycated hemoglobin of 7.0% to 10.5% (1298 participants) entered an 18- to 28-day screening period and were randomized 2:2:1 to once-weekly retatrutide 9 mg, once-weekly retatrutide 12 mg, or once-weekly semaglutide 2 mg, each added to metformin with or without a sodium-glucose cotransporter-2 inhibitor. Retatrutide was escalated through 2 mg, 4 mg, 6 mg, and 9 mg over the first 16 weeks before participants continued their randomized dose of 9 mg or 12 mg; semaglutide was escalated through 0.25 mg, 0.5 mg, and 1 mg before continuing at 2 mg. The primary endpoint was assessed at week 80, after which participants not entering the extension completed a first safety follow-up. Extension participants continued treatment through a 24-week extension treatment period to week 104, followed by a second safety follow-up.³

Abbreviations: HbA1c = glycated hemoglobin; Met = metformin; QW = once weekly; RETA = retatrutide; SEMA = semaglutide; SGLT2i = sodium-glucose cotransporter-2 inhibitor; T2D = type 2 diabetes.

^a Inadequate glycemic control with metformin ± SGLT2i.
^b Applicable only for the first 650 RETA participants completing 80 weeks on treatment.
^c 5 weeks ±7 days after the end of the treatment period for all participants.

The primary objective was to demonstrate that retatrutide 12 mg is noninferior to semaglutide 2 mg in HbA1c reduction at week 80.¹

Prespecified secondary endpoints included percent change in body weight, the proportions of participants achieving HbA1c and weight-reduction thresholds, percent change in triglycerides and non-high-density lipoprotein (non-HDL) cholesterol, and change in systolic blood pressure, all assessed at week 80.³

TRANSCEND-T2D-2 also includes an extension period in which approximately 650 participants continue treatment with retatrutide for an additional 24 weeks to evaluate long-term efficacy and safety.¹

Rationale for the Semaglutide 2 mg Comparator

TRANSCEND-T2D-2 compared retatrutide with semaglutide 2 mg because it is the highest approved dose of injectable semaglutide for type 2 diabetes, making it a meaningful point of comparison.¹

TRANSCEND-T2D-2 Inclusion and Exclusion Criteria

Please refer to Table 1 for key inclusion and exclusion criteria for TRANSCEND-T2D-2.³

**Table 1. TRANSCEND-T2D-2 Key Inclusion and Exclusion** **Criteria**³
Inclusion Criteria^a	Exclusion Criteria^a
Aged 18 years or older Diagnosis of T2D HbA1c, 7.0% (53 mmol/mol) to 10.5% (91 mmol/mol) Stable diabetes treatment consisting of metformin 1500 mg/d or more, with or without an SGLT2i, during the 90 days prior to screening Stable weight for at least 90 days prior to screening BMI of 25.0 kg/m² or higher	Type 1 diabetes History of ketoacidosis, hyperosmolar state, or coma within the 6 months prior to screening History of severe hypoglycemia or hypoglycemia unawareness within the 6 months prior to screening Currently receiving or planning to receive treatment for diabetic retinopathy or macular edema eGFR below 45 mL/min/1.73 m², or below the country-specific threshold for discontinuing metformin per local label Prior or planned surgical treatment for obesity New York Heart Association functional class IV congestive heart failure Acute myocardial infarction, stroke, or hospitalization for congestive heart failure within the 90 days prior to screening Known clinically significant gastric emptying abnormality History of an active or untreated malignancy, or remission from a clinically significant malignancy for less than 5 years Any lifetime history of a suicide attempt Chronic or acute pancreatitis Family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 Use of prescribed or over-the-counter medication, or alternative remedies, intended to promote body weight reduction within the 90 days prior to screening

Abbreviations: BMI = body mass index; eGFR = estimated glomerular filtration rate; HbA1c = glycated hemoglobin; SGLT2i = sodium-glucose cotransporter-2 inhibitor; T2D = type 2 diabetes.
^a Criteria as posted on ClinicalTrials.gov.

Back to Content Overview

What are the preliminary efficacy outcomes of TRANSCEND-T2D-2?

At week 80, retatrutide met the primary endpoint and all key secondary endpoints, with greater HbA1c reduction and more weight loss than semaglutide 2 mg (Table 2).¹

For all participants, the average baseline

HbA1c was 8.3%
body weight was 102.4 kg (225.8 lbs), and
body mass index was 36.8 kg/m².¹

**Table 2. Efficacy** **Estimand** **Outcomes at Week 80 in TRANSCEND-T2D-2**¹
Endpoint	Retatrutide 9 mg	Retatrutide 12 mg	Semaglutide 2 mg
Change in HbA1c, %	-2.2^a,b	-2.2^c	-1.8
Percent change in body weight, %	-19.5^c	-20.9^c	-9.4
Change in body weight, kg (lbs)	-20.1 (-44.3)	-21.5 (-47.4)	-9.5 (-20.9)

Abbreviation: HbA1c = glycated hemoglobin.
Note: All data are for the efficacy estimand, which represents efficacy had all randomized participants remained on study intervention (with possible dose interruptions and modifications) for 80 weeks without initiating additional antihyperglycemic medication (more than 14 days of use). Change in HbA1c at week 80 with retatrutide 12 mg was the primary endpoint; percent change in body weight was a key secondary endpoint.
^a Nominal p<.001 versus semaglutide 2 mg.
^b Noninferiority for change in HbA1c with retatrutide 9 mg versus semaglutide 2 mg was a key secondary endpoint.
^c p<.001 versus semaglutide 2 mg; family-wise type 1 error controlled for superiority.

All comparisons of retatrutide versus semaglutide 2 mg were controlled for family-wise type 1 error, except superiority of retatrutide 9 mg versus semaglutide 2 mg in change in HbA1c and in systolic blood pressure. These were prespecified secondary endpoints that showed nominal statistical significance. HbA1c noninferiority for retatrutide 9 mg vs semaglutide 2 mg was met under family-wise type 1 error control as a key secondary endpoint.¹

Back to Content Overview

What are the preliminary safety outcomes of TRANSCEND-T2D-2?

The most common adverse events (AEs) reported with retatrutide in TRANSCEND-T2D-2 were gastrointestinal-related AEs (Table 3). The majority of reported urinary tract infection and dysesthesia AEs were mild to moderate and typically resolved during treatment.¹

**Table 3.** **Selected** **Adverse Events in TRANSCEND-T2D-2**¹
Adverse Event	Retatrutide 9 mg, %	Retatrutide 12 mg, %	Semaglutide 2 mg, %
Diarrhea	28.3	32.7	26.4
Nausea	21.2	23.8	21.3
Constipation	14.2	13.1	19.8
Vomiting	10.2	15.0	13.2
Dyspepsia	10.4	8.5	11.6
Dysesthesia	4.8	6.5	2.7
Urinary tract infection	5.8	4.2	5.8
Discontinuation of study treatment due to an adverse event	4.8	7.9	2.7

Note: Data are percentages of participants. Participant counts and the denominator for each treatment group were not reported in the topline disclosure.

Back to Content Overview

What are the future expectations for retatrutide?

Detailed results from TRANSCEND-T2D-2 will be presented at a future medical meeting and published in a peer-reviewed journal. The extension period will provide an additional 24 weeks of efficacy and safety data in approximately 650 participants who continue treatment with retatrutide.¹

Back to Content Overview

References

The published reference below is available by contacting 1-800-LillyRx (1-800-545-5979).

Lilly's retatrutide delivered greater A1C reduction and more than double the weight loss of Ozempic's highest approved dose in head-to-head trial. Press release. Eli Lilly and Company; October 28, 2026. Accessed October 28, 2026. https://investor.lilly.com/news-releases/news-release-details/lillys-retatrutide-delivered-greater-a1c-reduction-and-more
Jastreboff AM, Kaplan LM, Frías JP, et al; Retatrutide Phase 2 Obesity Trial Investigators. Triple-hormone-receptor agonist retatrutide for obesity — a phase 2 trial. N Engl J Med. 2023;389(6):514-526. https://doi.org/10.1056/nejmoa2301972
Effect of retatrutide compared with semaglutide in adult participants with type 2 diabetes and inadequate glycemic control with metformin with or without SGLT2 inhibitor (TRANSCEND-T2D-2). ClinicalTrials.gov identifier: NCT06260722. Updated September 28, 2026. Accessed October 28, 2026. https://clinicaltrials.gov/study/NCT06260722

Date of Last Review: October 28, 2026

Are you satisfied with this content?