Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as LY3437943
Retatrutide · 24 trials · 17 indications
A composite endpoint includes nonfatal myocardial infarction (MI), nonfatal stroke, cardiovascular (CV) death, or hospitalization or urgent visit due to heart failure (HF).
ESKD is defined as the following individual components: persistent eGFR \<15 mL/min/1.73 m\^2 confirmed by 2 measurements at least 4 weeks apart at the central laboratory, initiation of dialysis for at least 28 days, receiving a kidney transplant. Sustained decline in eGFR (≥40%) will be confirmed by a repeated measure at least 4 weeks after the first result.
The GFR in milliliter/minute per1.73 square meter (mL/min/1.73 m²) using iohexol clearance (mGFR-measured glomerular filtration rate)
Least squares (LS) means were calculated using a mixed-effects model for repeated measures (MMRM) for post-baseline measures: Variable = Treatment\*Time + Baseline BMI (\< 36kg/m2 vs. \>=36 kg/m2)\*Time + Sex (Female vs. Male)\*Time + Baseline\*Time.
Change in HbA1c (%) from baseline in LY3437943 relative to placebo. HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least squares (LS) mean was calculated using mixed model repeated measures (MMRM) for post-baseline measures: Variable = Treatment\*Time + Strata\*Time + Baseline\*Time.
Time-to-event of recovery of PG concentration from 48 mg/dL to 70 mg/dL.
Change from baseline in total cDI for comparison of retatrutide with placebo
PK: AUC0-24 of Ethinyl Estradiol
PK: Cmax of Ethinyl Estradiol
PK: Tmax of Ethinyl Estradiol
PK: AUC0-24 of Drospirenone
PK: Cmax of Drospirenone
PK: Tmax of Drospirenone
A summary of TEAEs, SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module
PK: AUC\[0-∞\] of Midazolam
PK: Cmax of Midazolam
PK: AUC\[0-∞\] of Warfarin
PK: AUC\[0-∞\] of Caffeine
A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module
| Arm | Type | Description |
|---|---|---|
| Retatrutide Dose Escalation 1 | EXPERIMENTAL | Participants will receive retatrutide subcutaneously (SC) |
| Retatrutide Dose Escalation 2 | EXPERIMENTAL | Participants will receive retatrutide SC |
| Retatrutide Dose Escalation 3 | EXPERIMENTAL | Participants will receive retatrutide SC |
| Retatrutide Dose 1 | EXPERIMENTAL | Participants will receive retatrutide subcutaneously (SC) |
| Retatrutide Dose 2 | EXPERIMENTAL | Participants will receive retatrutide SC |
| Placebo | PLACEBO_COMPARATOR | Participants will receive placebo SC |
| Retatrutide | EXPERIMENTAL | Participants will receive Retatrutide subcutaneously (SC) |
| Retatrutide Dose 1 to Retatrutide Dose 2 | EXPERIMENTAL | Participants will receive retatrutide dose 1 administered SC for 80 weeks, then retatrutide dose 2 administered SC for an additional 36 weeks |
| Retatrutide Dose 1 to Placebo | PLACEBO_COMPARATOR | Participants will receive retatrutide dose 1 administered SC for 80 weeks, then placebo administered SC for an additional 36 weeks |
| Tirzepatide | ACTIVE_COMPARATOR | Participants will receive tirzepatide administered SC |
| Retatrutide Dose Level 1 | EXPERIMENTAL | Participants will receive retatrutide administered subcutaneously (SC). |
| Retatrutide Dose Level 2 | EXPERIMENTAL | Participants will receive retatrutide administered SC. |
| Retatrutide Dose Level 3 | EXPERIMENTAL | Participants will receive retatrutide administered SC. |
| Retatrutide Dose 3 | EXPERIMENTAL | Participants will receive retatrutide administered SC. |
| Semaglutide | ACTIVE_COMPARATOR | Participants will receive semaglutide administered SC. |
| Retatrutide Extension Period | EXPERIMENTAL | Participants will receive retatrutide after the placebo-controlled 80 week treatment period for an additional 24 weeks. |
| 1 milligram (mg) LY3437943 | EXPERIMENTAL | Participants received 1 mg LY3437943 administered as SC injection QW. |
| 4 mg LY3437943 (2 mg) | EXPERIMENTAL | Participants received 2 mg LY3437943 starting dose followed by 4 mg LY3437943 administered as SC injection QW. |
| 4 mg LY3437943 | EXPERIMENTAL | Participants received 4 mg LY3437943 administered as SC injection QW. |
| 8 mg LY3437943 (2 mg) | EXPERIMENTAL | Participants received 2 mg LY3437943 starting dose followed by 4 mg LY3437943 and then 8 mg LY3437943 administered as SC injection QW. |
| 8 mg LY3437943 (4 mg) | EXPERIMENTAL | Participants received 4 mg LY3437943 starting dose followed by 8 mg LY3437943 administered as SC injection QW. |
| 12 mg LY3437943 (2 mg) | EXPERIMENTAL | Participants received 2 mg LY3437943 starting dose followed by 4 mg LY3437943, 8 mg LY3437943 and then 12 mg LY3437943 administered as SC injection QW. |
| 0.5 milligrams (mg) LY3437943 | EXPERIMENTAL | Participants received 0.5 mg LY3437943 administered as SC (subcutaneous) injection once weekly (QW). |
| 4 mg LY3437943 (4 mg) | EXPERIMENTAL | Participants received 4 mg LY3437943 administered as SC injection QW. |
| 1.5 mg Dulaglutide | ACTIVE_COMPARATOR | Participants received 1.5 mg dulaglutide administered as SC single-dose pen injection QW. |
| LY3437943 | EXPERIMENTAL | LY3437943 administered subcutaneously (SC) |
| LY3437943 + Combined Oral Contraceptive (COC) | EXPERIMENTAL | The COC ethinyl estradiol and drospirenone administered orally in combination with LY3437943 administered subcutaneously (SC). |
| LY3437943 + Drug Cocktail | EXPERIMENTAL | Midazolam in combination with warfarin and caffeine (drug cocktail) administered orally followed by LY3437943 administered subcutaneously (SC) in week 1. At weeks 8, 12, \& 16, the LY3437943 will be administered SC on Day 1 followed by midazolam in combination with warfarin and caffeine (drug cocktail) administered orally on Day 2. |
| Dulaglutide | ACTIVE_COMPARATOR | Dulaglutide administered SC |
| Name | Type | Description |
|---|---|---|
| Retatrutide | DRUG | Administered SC |
| Placebo | DRUG | Administered SC |
| Tirzepatide | DRUG | Administered SC |
| Semaglutide | DRUG | Administered SC. |
| LY3437943 | DRUG | Administered SC |
| Dulaglutide | DRUG | Administered SC |
| Ethinyl Estradiol | DRUG | Administered orally |
| Drospirenone | DRUG | Administered orally |
| Midazolam | DRUG | Administered orally. |
| Warfarin | DRUG | Administered orally. |
| Caffeine | DRUG | Administered orally. |
Inclusion Criteria: * Have a Body Mass Index (BMI) at screening * ≥ 30 kilogram per square meter (kg/m2) OR * ≥ 27 kg/m2 with presence of at least one of the following weight-related conditions at screening: high blood pressure, abnormal levels of lipid, obstructive sleep apnea, heart disease ...
Retatrutide is an investigational small molecule developed by Eli Lilly and Company for obesity, overweight, type 2 diabetes mellitus, and atherosclerotic cardiovascular disease. It is in Phase 3 clinical development and has been studied in randomized, double-blind, placebo-controlled trials. It is not yet approved for any indication.
Retatrutide targets GIPR, GLP1R, and GCGR, acting as an agonist at all three receptors. This triple agonist profile distinguishes it from single or dual incretin therapies. The combined receptor activity is the basis for its investigation in metabolic and cardiovascular conditions.
Retatrutide is being studied for obesity, overweight, type 2 diabetes mellitus, and atherosclerotic cardiovascular disease. Clinical trials have also enrolled participants with chronic low back pain alongside obesity or overweight. It remains investigational and has not been approved for any of these uses.
Retatrutide is developed by Eli Lilly and Company, which trades on the New York Stock Exchange under the ticker LLY. Lilly sponsors the clinical trial program, including the Phase 3 obesity studies and the Phase 1 type 2 diabetes study.
Retatrutide is in Phase 3 clinical development. Eight trials have been conducted in total, with five currently active and three completed. The program includes Phase 3 studies in obesity and overweight and a Phase 1 study in type 2 diabetes mellitus.
Retatrutide trials include NCT07357415 and NCT07232719 in obesity or overweight, NCT07035093 in obesity or overweight with chronic low back pain, and NCT06982859 in type 2 diabetes mellitus. These studies are randomized, double-blind, and placebo-controlled, with total enrollment across the program of about 10,000 participants.