K4 Elite
K4 Elite
Retatrutide (LY3437943) is a once-weekly single-peptide agonist of the GIP, GLP-1 and glucagon receptors developed by Eli Lilly. It has been studied in randomised, double-blind, placebo-controlled Phase 2 trials in adults with obesity (NEJM 2023) and type 2 diabetes (Lancet 2023), a Phase 2a MASLD substudy (Nature Medicine 2024), and a Phase 3 programme (TRIUMPH obesity trials; TRANSCEND type 2 diabetes trials), of which TRANSCEND-T2D-1 is peer-reviewed (Lancet 2026) and TRIUMPH-1 has so far been reported only in a sponsor press release. It is investigational and not approved by any regulator.
Each row records what a published study did: who it enrolled, the regimen it administered to those subjects, and what it reported. These are historical study descriptions, not protocols to follow.
| Study | Population | Regimen as reported | Primary findings |
|---|---|---|---|
| Jastreboff et al., NEJM 2023 (Phase 2, obesity) Registry: NCT04881760
|
Adults with BMI >=30, or 27 to <30 plus at least one weight-related condition, without diabetes (n=338) | Participants were randomly assigned to subcutaneous retatrutide 1 mg, 4 mg (initial dose 2 mg or 4 mg), 8 mg (initial dose 2 mg or 4 mg) or 12 mg (initial dose 2 mg), or placebo, once weekly for 48 weeks. | Least-squares mean percentage change in body weight at 24 weeks was -7.2% (1 mg), -12.9% (4 mg), -17.3% (8 mg) and -17.5% (12 mg) versus -1.6% with placebo; at 48 weeks it was -8.7%, -17.1%, -22.8% and -24.2% versus -2.1%. |
| Rosenstock et al., Lancet 2023 (Phase 2, type 2 diabetes) Registry: NCT04867785
|
Adults aged 18-75 with type 2 diabetes, HbA1c 7.0-10.5%, BMI 25-50 kg/m2, on diet/exercise or stable metformin (n=281 randomised) | Participants received once-weekly injections of placebo, dulaglutide 1.5 mg, or retatrutide maintenance doses of 0.5 mg, 4 mg (starting dose 2 mg), 4 mg (no escalation), 8 mg (starting dose 2 mg), 8 mg (starting dose 4 mg) or 12 mg (starting dose 2 mg) for 36 weeks. | At 24 weeks, least-squares mean change in HbA1c ranged from -0.43% (0.5 mg) to -2.02% (12 mg escalation group) versus -0.01% with placebo and -1.41% with dulaglutide 1.5 mg; body weight decreased dose-dependently by up to 16.94% at 36 weeks. |
| Sanyal et al., Nature Medicine 2024 (Phase 2a MASLD substudy) Registry: NCT04881760
|
Participants from the Phase 2 obesity trial with metabolic dysfunction-associated steatotic liver disease and >=10% liver fat (n=98) | Participants were randomly assigned to 48 weeks of once-weekly subcutaneous retatrutide (1, 4, 8 or 12 mg) or placebo. | Mean relative change from baseline in liver fat at 24 weeks was -42.9% (1 mg), -57.0% (4 mg), -81.4% (8 mg), -82.4% (12 mg) and +0.3% (placebo). |
| TRANSCEND-T2D-1, Lancet 2026 (Phase 3, type 2 diabetes) Registry: NCT06354660
|
Adults with type 2 diabetes inadequately controlled by diet and exercise, HbA1c 7.0-9.5%, BMI >=23 kg/m2 (n=537 randomised; 48 sites in USA, Mexico, India) | Participants were randomly assigned 1:1:1:1 to retatrutide 4 mg, 9 mg or 12 mg, or placebo, by once-weekly subcutaneous injection for 40 weeks. | Mean change in HbA1c from baseline to week 40 was -1.69% (4 mg), -1.86% (9 mg) and -1.94% (12 mg) versus -0.81% with placebo; mean body-weight change was -11.5%, -13.9% and -15.3% versus -2.6%. |
| TRIUMPH-1 (Phase 3, obesity) — sponsor topline press release, May 2026; not yet peer-reviewed Registry: NCT05929066
|
Adults with obesity, or overweight with at least one weight-related comorbidity, without diabetes (n=2,339 randomised) | Participants were randomised 1:1:1:1 to retatrutide 4 mg, 9 mg or 12 mg, or placebo, once weekly for 80 weeks; retatrutide arms initiated at 2 mg with step-wise escalation every four weeks to the target dose. A pre-specified extension to 104 weeks enrolled 532 participants with BMI >=35. | Sponsor-reported efficacy-estimand percentage change in body weight at 80 weeks was -19.0% (4 mg), -25.9% (9 mg) and -28.3% (12 mg) versus -2.2% with placebo; treatment-regimen estimand values were -17.6%, -23.7%, -25.0% and -3.9%. |
Effects recorded in the cited reports. Frequencies are those the source reported, in the population that source studied.
| Effect | Frequency / context | Source |
|---|---|---|
| Gastrointestinal events (nausea, diarrhoea, vomiting, constipation) | Most common adverse events in the Phase 2 obesity trial; dose-related, mostly mild to moderate, and partially mitigated by a 2 mg rather than 4 mg starting dose (Jastreboff et al., NEJM 2023). | Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial ↗ |
| Gastrointestinal events (mild-to-moderate) | Reported in 67 of 190 (35%) retatrutide participants (range 13% at 0.5 mg to 50% at 8 mg fast escalation) versus 13% placebo and 35% dulaglutide 1.5 mg in the Phase 2 type 2 diabetes trial (Rosenstock et al., Lancet 2023). | Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA ↗ |
| Nausea | 28.6% (4 mg), 38.4% (9 mg), 42.4% (12 mg) vs 14.8% placebo over 80 weeks (TRIUMPH-1, sponsor press release). | Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial (Eli Lilly press release, 21 May 2026) ↗ |
| Diarrhoea | 25.2% (4 mg), 34.1% (9 mg), 32.0% (12 mg) vs 13.5% placebo (TRIUMPH-1, sponsor press release). | Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial (Eli Lilly press release, 21 May 2026) ↗ |
| Constipation | 23.8% (4 mg), 25.9% (9 mg), 26.1% (12 mg) vs 10.9% placebo (TRIUMPH-1, sponsor press release). | Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial (Eli Lilly press release, 21 May 2026) ↗ |
| Vomiting | 10.6% (4 mg), 22.8% (9 mg), 25.3% (12 mg) vs 4.8% placebo (TRIUMPH-1, sponsor press release). | Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial (Eli Lilly press release, 21 May 2026) ↗ |
| Dysesthesia (altered skin sensation) | 5.1% (4 mg), 12.3% (9 mg), 12.5% (12 mg) vs 0.9% placebo in TRIUMPH-1; described by the sponsor as generally mild to moderate, with the majority resolving during treatment. This signal was not described in the Phase 2 abstracts. | Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial (Eli Lilly press release, 21 May 2026) ↗ |
| Urinary tract infection | 7.5% (4 mg), 8.8% (9 mg), 8.4% (12 mg) vs 5.3% placebo (TRIUMPH-1, sponsor press release). | Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial (Eli Lilly press release, 21 May 2026) ↗ |
| Discontinuation due to adverse events | 4.1% (4 mg), 6.9% (9 mg), 11.3% (12 mg) vs 4.9% placebo in TRIUMPH-1 (sponsor press release); 2-5% with retatrutide vs 0% placebo in TRANSCEND-T2D-1 (Lancet 2026). | Efficacy and safety of retatrutide ... (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial ↗ |
| Increase in heart rate | Dose-dependent increases in heart rate peaked at 24 weeks and declined thereafter in the Phase 2 obesity trial (Jastreboff et al., NEJM 2023). | Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial ↗ |
| Hypoglycaemia | No severe hypoglycaemia was reported in the Phase 2 type 2 diabetes trial (Lancet 2023) or in TRANSCEND-T2D-1 (Lancet 2026). | Efficacy and safety of retatrutide ... (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial ↗ |
Interactions documented in trial reports, prescribing information or pharmacology references.
| Agent | Type | Note | Source |
|---|---|---|---|
| Metformin (background therapy) | study co-administration | In the Phase 2 type 2 diabetes trial, participants were treated with diet and exercise alone or a stable dose of metformin (>=1000 mg once daily); no formal interaction study is described in the abstract. | Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA ↗ |
Exclusions and label contraindications recorded in the cited sources.