Lilly's triple agonist, retatrutide, demonstrated significant reductions in A1C and weight in first Phase 3 trial for treatment of type 2 diabetes

Rhea-AI Summary

Eli Lilly (NYSE: LLY) reported positive topline Phase 3 results for retatrutide in TRANSCEND-T2D-1 on March 19, 2026. At 40 weeks, retatrutide produced up to 2.0% A1C reduction and up to 16.8% weight loss (36.6 lbs) versus placebo, meeting primary and all key secondary endpoints.

Improvements were seen across doses (4 mg, 9 mg, 12 mg) and cardiovascular risk markers; common adverse events were nausea, diarrhea and vomiting, mostly during dose escalation.

Positive

• A1C reduction up to 2.0% at 40 weeks
• Weight loss up to 16.8% (36.6 lbs) at 40 weeks
• All primary and key secondary endpoints met in TRANSCEND-T2D-1
• Observed improvements in non-HDL cholesterol, triglycerides, and systolic blood pressure

Negative

• Higher rates of gastrointestinal adverse events (nausea up to 26.5%)
• Discontinuation due to adverse events up to 5.1% at 12 mg
• Incidence of dysesthesia reported in up to 4.5% of treated patients

News Market Reaction – LLY

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-0.06% News Effect

On the day this news was published, LLY declined 0.06%, reflecting a mild negative market reaction.

Data tracked by StockTitan Argus on the day of publication.

Key Figures

A1C reduction: up to 2.0% Weight loss at 12 mg: 36.6 lbs (16.8%) Baseline A1C: 7.9% +5 more

8 metrics

A1C reduction up to 2.0% Primary endpoint at 40 weeks, efficacy estimand vs baseline 7.9%

Weight loss at 12 mg 36.6 lbs (16.8%) Key secondary endpoint, efficacy estimand at 40 weeks

Baseline A1C 7.9% Starting HbA1c level for TRANSCEND‑T2D‑1 participants

Baseline body weight 96.9 kg (213.6 lbs; BMI 35.8 kg/m²) Mean starting weight and BMI for trial participants

Placebo weight change -2.5% (-2.8 kg; -6.2 lbs) Body weight change at 40 weeks, efficacy estimand

Nausea at 12 mg 26.5% vs 3.7% placebo Most common adverse event during dose escalation

Diarrhea at 9 mg 26.3% vs 4.5% placebo Gastrointestinal adverse event incidence

Discontinuations at 12 mg 5.1% vs 0.0% placebo Discontinuation rate due to adverse events

Market Reality Check

Price: $917.50 Vol: Volume 3,428,609 vs 20-da...

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$917.50 Last Close

Volume Volume 3,428,609 vs 20-day average 2,917,713 (relative volume 1.18x). normal

Technical Price 918.05 trades above 200-day MA 890.93, but is 19.04% below 52-week high.

Peers on Argus

LLY fell 1.32% with above-average volume while large-cap peers mostly declined (...

LLY fell 1.32% with above-average volume while large-cap peers mostly declined (ABBV -4.65, AZN -1.18, NVS -1.69, JNJ -0.25), and NVO was roughly flat (0.03). Momentum scanners did not flag a broad sector move.

Previous Clinical trial Reports

5 past events · Latest: Mar 16 (Positive)

Same Type Pattern 5 events

Date	Event	Sentiment	Move	Catalyst
Mar 16	Phase 3 AD data	Positive	-0.2%	EBGLYSS Phase 3 pediatric atopic dermatitis met key efficacy endpoints.
Dec 18	Phase 3 obesity data	Positive	+1.4%	Orforglipron maintained weight loss after switching from injectable incretins.
Dec 11	Retatrutide Phase 3	Positive	+1.6%	Retatrutide delivered large weight loss and pain relief in obesity with OA.
Dec 07	Jaypirca head-to-head	Positive	-1.3%	Jaypirca met non‑inferiority vs Imbruvica with favorable safety signals.
Nov 24	Jaypirca ASH data	Positive	+1.0%	Two positive Phase 3 Jaypirca studies highlighted for upcoming ASH meeting.

Pattern Detected

Positive clinical trial readouts for LLY have often produced modest single-day moves, with a mix of aligned and divergent reactions versus the positive tone.

Recent Company History

Over recent months, Lilly has repeatedly reported positive Phase 3 data across multiple programs. In Nov 2025 and Dec 2025, Jaypirca and retatrutide clinical results showed strong efficacy and safety, followed by favorable obesity and weight-maintenance data for orforglipron on Dec 18, 2025. On Mar 16, 2026, EBGLYSS achieved robust pediatric atopic dermatitis outcomes. Today’s TRANSCEND‑T2D‑1 trial update for retatrutide in type 2 diabetes extends this pattern of positive late-stage readouts across cardiometabolic and immunology franchises.

Historical Comparison

+0.5% avg move · In the past 12 months, LLY’s 5 clinical trial updates moved the stock an average of 0.5%, indicating...

clinical trial

+0.5%

Average Historical Move clinical trial

In the past 12 months, LLY’s 5 clinical trial updates moved the stock an average of 0.5%, indicating generally modest single-day reactions to positive data.

Clinical news shows progression across franchises: Jaypirca data maturing in CLL, retatrutide advancing from Phase 3 obesity/osteoarthritis results to type 2 diabetes, and EBGLYSS expanding into pediatric atopic dermatitis, underscoring a broad late-stage portfolio.

Market Pulse Summary

This announcement highlights Phase 3 TRANSCEND‑T2D‑1 results showing A1C reductions up to 2.0% and w...

Analysis

This announcement highlights Phase 3 TRANSCEND‑T2D‑1 results showing A1C reductions up to 2.0% and weight loss of 16.8% at 40 weeks for retatrutide in type 2 diabetes, along with improvements in cardiovascular risk markers. The data build on earlier retatrutide obesity findings and Lilly’s broader late-stage pipeline. Key factors to watch include full safety details, durability beyond 40 weeks, comparative positioning versus other incretin therapies, and outcomes from additional Phase 3 studies over the next year.

Key Terms

a1c, bmi, non-hdl cholesterol, triglycerides, +4 more

8 terms

a1c medical

"For the primary endpoint, retatrutide lowered A1C by an average of 1.7% to 2.0%"

A1C is a blood test that reports average blood sugar over about three months by measuring how much glucose sticks to hemoglobin, a protein in red blood cells. For investors, A1C acts like a long-term scorecard for diabetes treatments, devices and diagnostics: meaningful changes in A1C in clinical studies can affect regulatory approval, insurance coverage and commercial prospects, and thus influence a company's market value.

bmi medical

"from a baseline of 96.9 kg (213.6 lbs; BMI of 35.8 kg/m 2 )"

Body mass index (BMI) is a simple number calculated from a person’s weight and height that classifies them as underweight, normal weight, overweight, or obese; think of it as a quick ratio like miles per gallon for body size. Investors watch BMI because shifts in population averages influence demand for healthcare services, drugs, medical devices, and insurance costs, and they can signal longer-term trends in workforce health and public spending.

non-hdl cholesterol medical

"improvements from baseline across key cardiovascular risk factors, including non-HDL cholesterol"

Non-HDL cholesterol is the total amount of blood cholesterol carried by all particles that can clog arteries, calculated by subtracting 'good' HDL cholesterol from total cholesterol; think of it as counting all the cars that can cause traffic jams rather than just one type. It matters to investors because higher non-HDL levels predict greater risk of heart disease across populations, which can influence healthcare costs, workforce productivity, insurance liabilities, and demand for drugs or medical services.

triglycerides medical

"key cardiovascular risk factors, including non-HDL cholesterol, triglycerides and systolic blood pressure."

Triglycerides are the main form of fat carried in the bloodstream, made from excess calories and used by the body for energy or stored in fat tissue; think of them as the oil reserves that fuel the body. They matter to investors because high or low levels influence demand for drugs, diagnostics, and healthcare services, affect regulatory reviews and insurance costs, and signal population health trends that can change market size and company risk.

systolic blood pressure medical

"risk factors, including non-HDL cholesterol, triglycerides and systolic blood pressure."

Systolic blood pressure is the top number in a blood pressure reading, measuring the pressure in your arteries when your heart beats and pumps blood. It indicates how forcefully the heart pushes blood through the body. For investors, it can symbolize the maximum stress or intensity in a system, helping to assess overall health risks or stability.

placebo medical

"weight loss at 40 weeks compared to placebo, using both the efficacy"

A placebo is an inactive pill, injection or procedure that looks and feels like the real treatment but contains no therapeutic ingredient, often called a sugar pill. Investors care because comparing a drug to a placebo reveals whether observed benefits come from the medicine itself or from expectation; clear superiority over placebo reduces regulatory and commercial risk, much like a blind taste test proves a new recipe really tastes better.

estimand technical

"compared to placebo, using both the efficacy and treatment-regimen estimands."

An estimand is the specific question a clinical study is designed to answer about a treatment’s effect — essentially the exact outcome the researchers will measure after deciding how to handle things that happen during the study, such as patients leaving, starting other treatments, or changing doses. For investors, the estimand matters because it determines how trial results should be interpreted and compared, like knowing whether a scoreboard counts only players who stayed the whole game or everyone who started it, which affects risk and valuation judgments.

dysesthesia medical

"Incidence of dysesthesia occurred in 4.5%, 2.3% and 4.4%"

Dysesthesia is a medical condition in which people feel unpleasant, abnormal sensations—such as burning, electric shocks, itching, or numbness—that can occur without any external cause or from a light touch. For investors, reports of dysesthesia matter because they signal potential safety or tolerability issues for drugs, medical devices, or treatments; such side effects can affect regulatory approval, labeling, market acceptance, and ultimately a product’s commercial prospects, similar to a consumer product gaining a reputation for causing discomfort.

AI-generated analysis. Not financial advice.

For the primary endpoint, retatrutide lowered A1C by an average of 1.7% to 2.0% across doses at 40 weeks in TRANSCEND-T2D-1

Participants taking retatrutide 12 mg lost an average of 36.6 lbs (16.8%)

No weight loss plateau was observed with retatrutide, with participants continuing their weight loss trajectory through 40 weeks

INDIANAPOLIS, March 19, 2026 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced positive topline results from TRANSCEND-T2D-1, a Phase 3 clinical trial evaluating the efficacy and safety of retatrutide, an investigational first-in-class GIP, GLP-1 and glucagon triple hormone receptor agonist, as an adjunct to diet and exercise. The trial enrolled adults diagnosed with type 2 diabetes with inadequate glycemic control with diet and exercise alone, and a mean duration of diabetes of 2.5 years. In the study, retatrutide met the primary and all key secondary endpoints, delivering superior A1C reduction and weight loss at 40 weeks compared to placebo, using both the efficacy and treatment-regimen estimands.^1,2 For the primary endpoint, participants taking retatrutide achieved average A1C reductions of up to 2.0%, using the efficacy estimand. For a key secondary endpoint, participants taking retatrutide lost up to an average of 36.6 lbs (16.8%), using the efficacy estimand. Weight loss continued through the end of the treatment period.

"For many people with type 2 diabetes, it is a struggle to achieve both A1C control and weight loss, since obesity has historically been harder to treat for those with type 2 diabetes," said Kenneth Custer, Ph.D., executive vice president and president, Lilly Cardiometabolic Health. "With triple agonist retatrutide, we set out to make a molecule that could help patients achieve substantial A1C reduction and weight loss. These results support the remarkable potential of this novel molecule for people living with type 2 diabetes, with up to 2% A1C improvement and nearly 17% weight loss in 40 weeks of treatment."

TRANSCEND-T2D-1 Efficacy Results

Primary Endpoint
		Retatrutide 4 mg	Retatrutide 9 mg	Retatrutide 12 mg	Placebo
Change in A1C from a baseline of 7.9% at 40 weeks	Efficacy estimand	-1.7 %	-2.0 %	-1.9 %	-0.8 %
	Treatment- regimen estimand	-1.7 %	-1.9 %	-1.9 %	-0.8 %
Key Secondary Endpoint
Percentage change in body weight at 40 weeks from a baseline of 96.9 kg (213.6 lbs; BMI of 35.8 kg/m2)	Efficacy estimand	-11.5%     (-11.1 kg;  -24.5 lbs)	-15.5%     (-15.1 kg;  -33.3 lbs)	-16.8%     (-16.6 kg;  -36.6 lbs)	-2.5%     (-2.8 kg;  -6.2 lbs)
	Treatment- regimen estimand	-11.5%    (-11.1 kg; -24.5 lbs)	-13.9%    (-13.5 kg; -29.8 lbs)	-15.3%    (-15.1 kg; -33.3 lbs)	-2.6%    (-2.7 kg; -6.0 lbs)

Retatrutide also showed clinically meaningful improvements from baseline across key cardiovascular risk factors, including non-HDL cholesterol, triglycerides and systolic blood pressure.³

Consistent with the types of adverse events seen in clinical trials for other incretin-based therapies, the most common adverse events among participants treated with retatrutide (4 mg, 9 mg, 12 mg) were nausea (16.4%, 19.5%, 26.5%, respectively vs. 3.7% with placebo), diarrhea (18.7%, 26.3%, 22.8%, respectively vs. 4.5% with placebo) and vomiting (15.7%, 15.0%, 17.6%, respectively vs. 2.2% with placebo), and occurred primarily during dose escalation. Incidence of dysesthesia occurred in 4.5%, 2.3% and 4.4% (4 mg, 9 mg and 12 mg, respectively) of patients treated with retatrutide, compared to 0.0% with placebo. These dysesthesia events were generally mild, with a majority resolving during treatment. Discontinuation rates due to adverse events were 2.2%, 4.5% and 5.1% with retatrutide 4 mg, 9 mg and 12 mg, respectively, compared to 0.0% with placebo.

Detailed TRANSCEND-T2D-1 results will be presented at the American Diabetes Association Scientific Sessions in June and published in a peer-reviewed journal. Additional results from the retatrutide clinical trial program are expected over the next year.

About retatrutide
Retatrutide is an investigational once-weekly triple hormone receptor agonist. Retatrutide is a single molecule that activates the body's receptors for glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon. Lilly is studying retatrutide in several Phase 3 clinical trials to evaluate its potential efficacy and safety in obesity and overweight with at least one weight-related medical problem, type 2 diabetes, knee osteoarthritis, moderate-to-severe obstructive sleep apnea, chronic low back pain, cardiovascular and renal outcomes, and metabolic dysfunction-associated steatotic liver disease. Retatrutide is an investigational molecule that is legally available only to participants in Lilly's clinical trials.

About TRANSCEND-T2D-1 and the TRANSCEND-T2D clinical trial program
TRANSCEND-T2D-1 (NCT06354660) is a Phase 3, 40-week, randomized, double-blind, placebo-controlled study comparing the efficacy and safety of retatrutide with placebo in adults with type 2 diabetes and inadequate glycemic control with diet and exercise alone. The study randomized 537 participants in a 1:1:1:1 ratio to receive either retatrutide 4 mg, 9 mg or 12 mg, or placebo. The objective of the study was to demonstrate that retatrutide (4 mg, 9 mg or 12 mg) is superior to placebo in A1C reduction from baseline after 40 weeks, in adults with type 2 diabetes who have not taken any anti-diabetes medications for at least 90 days prior to visit one, and are naïve to insulin therapy except for gestational diabetes. Study participants had A1C between ≥7.0% and ≤9.5% and a BMI of ≥23 kg/m² at visit one. Participants randomized to retatrutide initiated treatment with 2 mg once-weekly and increased the dose in a step-wise approach every four weeks until reaching the target dose of 4 mg (via one step at 2 mg), 9 mg (via steps at 2 mg, 4 mg and 6 mg) or 12 mg (via steps at 2 mg, 4 mg, 6 mg and 9 mg).

The TRANSCEND-T2D Phase 3 clinical trial program is evaluating the safety and efficacy of retatrutide for the treatment of adults with type 2 diabetes across three global registrational trials. The program, which began in 2024, has enrolled more than 2,050 participants and additional results are anticipated over the next year.

Endnotes and References 

1. The efficacy estimand represents efficacy had all randomized participants remained on study intervention (with possible dose interruptions and/or dose modifications) for 40 weeks without initiating additional antihyperglycemic medications (>14 days of use). 
2. The treatment-regimen estimand represents the estimated average treatment effect regardless of adherence to study intervention or initiation of additional antihyperglycemic medications. 
3. Reduction in non-HDL cholesterol, triglycerides and systolic blood pressure with retatrutide was controlled for family-wise type 1 error in all dose groups except for 4 mg.

About Lilly
Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news, or follow us on Facebook, Instagram and LinkedIn. P-LLY

Cautionary Statement Regarding Forward-Looking Statements
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about retatrutide as a potential treatment for adults with type 2 diabetes, potential efficacy and tolerability of retatrutide, and the timeline for future readouts, presentations, and other milestones relating to retatrutide and its clinical trials and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there is no guarantee that planned or ongoing studies will be completed as planned, that future study results will be consistent with expectations or study results to date, that retatrutide will prove to be a safe and effective treatment for type 2 diabetes or other potential indications, that retatrutide will receive regulatory approval, or that Lilly will execute its strategy as expected. For further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, see Lilly's Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release. 

Trademarks and Trade Names 
All trademarks or trade names referred to in this press release are the property of the company, or, to the extent trademarks or trade names belonging to other companies are referenced in this press release, the property of their respective owners. Solely for convenience, the trademarks and trade names in this press release are referred to without the ^® and ™ symbols, but such references should not be construed as any indicator that the company or, to the extent applicable, their respective owners will not assert, to the fullest extent under applicable law, the company's or their rights thereto. We do not intend the use or display of other companies' trademarks and trade names to imply a relationship with, or endorsement or sponsorship of us by, any other companies.

Refer to:	Niki Biro; niki_biro@lilly.com; 317-358-9074 (Media)
	Michael Czapar; czapar_michael_c@lilly.com; 317-617-0983 (Investors)

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SOURCE Eli Lilly and Company

FAQ

What did Lilly (LLY) announce on March 19, 2026 about retatrutide in TRANSCEND-T2D-1?

Lilly announced that retatrutide met primary and key secondary endpoints with substantial A1C and weight reductions. According to the company, retatrutide produced up to 2.0% A1C reduction and up to 16.8% weight loss (36.6 lbs) at 40 weeks versus placebo.

How much weight did patients on retatrutide 12 mg lose in TRANSCEND-T2D-1 (LLY)?

Patients on retatrutide 12 mg lost an average of 36.6 lbs (16.8%) at 40 weeks. According to the company, weight loss showed no plateau and continued through the 40-week treatment period.

What A1C improvements were reported for retatrutide in the TRANSCEND-T2D-1 trial (LLY)?

Retatrutide lowered A1C by up to 2.0 percentage points at 40 weeks across doses. According to the company, reductions ranged approximately from 1.7% to 2.0% using the efficacy estimand.

What were the most common side effects of retatrutide in TRANSCEND-T2D-1 (LLY)?

The most common side effects were gastrointestinal: nausea, diarrhea and vomiting, occurring mainly during dose escalation. According to the company, nausea rates reached 26.5% at the highest dose versus 3.7% for placebo.

When will detailed TRANSCEND-T2D-1 data for retatrutide (LLY) be presented and published?

Detailed results will be presented at the American Diabetes Association Scientific Sessions in June and submitted for peer review. According to the company, full trial data will also be published in a peer-reviewed journal thereafter.