California telemedicine • GLP-1 / GIP / glucagon research
Retatrutide Therapy in California
Physician-guided review for an investigational next-generation metabolic therapy targeting GLP-1, GIP, and glucagon pathways.
Retatrutide is a triple hormone receptor agonist being studied for weight management, glycemic control, liver fat reduction, insulin resistance, and cardiometabolic risk markers. MyFlowMD provides physician-guided review and education for California patients interested in advanced metabolic care. Treatment decisions depend on clinical appropriateness, availability, medical history, and clinician review.
What is retatrutide?
Retatrutide, also known as LY3437943, is a single peptide designed to activate three hormone receptor pathways involved in appetite, glucose regulation, lipid metabolism, and energy balance:
- GLP-1 receptor
- GIP receptor
- Glucagon receptor
It is not simply a stronger GLP-1. The glucagon receptor component may contribute to effects on liver fat, fatty-acid oxidation, lipid metabolism, and energy expenditure, but those mechanisms should not be overstated as guaranteed clinical outcomes for individual patients.
Published peer-reviewed evidence summary
The strongest published human evidence for retatrutide currently supports substantial effects on weight loss, glycemic control, liver fat, insulin resistance, body composition, and several cardiometabolic markers. Trial results are averages from selected research populations and are not guarantees for individual patients.
Weight loss
Up to approximately 24.2% mean body-weight reduction at 48 weeks in a phase 2 obesity trial.
Type 2 diabetes
HbA1c reductions around 1.7–2.0 percentage points were reported in published phase 2 and phase 3 trials.
Liver fat
Approximately 86% relative reduction in liver fat at 48 weeks was reported in a MASLD phase 2a substudy.
Insulin resistance
HOMA2-IR improvement up to approximately 69% was reported in the MASLD analysis.
Body composition
Body-composition data show substantial fat-mass reduction. Current evidence should not be framed as unique muscle preservation.
Cardiometabolic markers
Trials reported improvements in waist circumference, triglycerides, blood pressure, glucose, insulin, and lipid markers.
Obesity / weight loss: phase 2 trial
In a randomized phase 2 trial of 338 adults with obesity or overweight plus a weight-related condition, without diabetes, mean weight loss at 48 weeks reached approximately 17.1% with 4 mg, 22.8% with 8 mg, and 24.2% with 12 mg, compared with approximately 2.1% with placebo. Weight loss was still progressing at 48 weeks. Improvements were also reported in waist circumference, blood pressure, fasting glucose, HbA1c, fasting insulin, triglycerides, and lipid markers.
Source: Jastreboff AM, Kaplan LM, Frias JP, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. New England Journal of Medicine. 2023;389:514-526. DOI: 10.1056/NEJMoa2301972.
Type 2 diabetes: phase 2 trial
In a randomized phase 2 trial in adults with type 2 diabetes, retatrutide produced clinically meaningful improvements in glycemic control and body weight. HbA1c reductions approached approximately 2 percentage points, and weight loss approached approximately 17% at higher-dose regimens.
Source: Rosenstock J, Frias J, Jastreboff AM, et al. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes. The Lancet. 2023;402:529-544. DOI: 10.1016/S0140-6736(23)01053-X.
Type 2 diabetes: phase 3 trial
In the TRANSCEND-T2D-1 phase 3 trial, adults with inadequately controlled type 2 diabetes treated with diet and exercise alone received retatrutide or placebo for 40 weeks. Retatrutide reduced HbA1c by approximately 1.7 to 2.0 percentage points depending on dose, and the 12 mg group lost approximately 16.8% of body weight. The weight-loss trajectory had not clearly plateaued at 40 weeks.
Source: Bajaj HS, Welch M, Shah P, et al. Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1). The Lancet. 2026. DOI: 10.1016/S0140-6736(26)00967-0.
MASLD / liver fat: phase 2a substudy
In a MASLD substudy using MRI-based liver-fat measurement, the 12 mg dose produced approximately 86% mean relative reduction in liver fat at 48 weeks. Liver fat below 5% was achieved in approximately 89% of participants receiving 8 mg and 93% receiving 12 mg. The study also reported improvements in fasting insulin, C-peptide, HOMA2-IR, triglycerides, adiponectin, leptin, and selected liver injury or fibrogenesis-related biomarkers.
These liver-fat findings are biologically interesting, but they should not be interpreted as proof of fibrosis regression, MASH resolution, or long-term liver outcome benefit.
Source: Sanyal AJ, Kaplan LM, Frias JP, et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nature Medicine. 2024. DOI: 10.1038/s41591-024-03018-2.
Body composition
A body-composition substudy in people with type 2 diabetes found that retatrutide produced substantial total fat-mass reduction. Some lean-mass loss occurred, as expected with major weight loss. Current evidence does not establish that retatrutide uniquely preserves skeletal muscle.
Source: Coskun T, Wu Q, Schloot NC, et al. Effects of retatrutide on body composition in people with type 2 diabetes. The Lancet Diabetes & Endocrinology. 2025;13(8):674–684. DOI: 10.1016/S2213-8587(25)00092-0.
Early human proof-of-concept
The original phase 1b study in people with type 2 diabetes demonstrated early signals for glucose lowering, HbA1c lowering, weight reduction, and pharmacokinetics compatible with once-weekly dosing. Because it was small and early-stage, it should be treated as proof-of-concept evidence rather than definitive therapeutic evidence.
Source: Urva S, Coskun T, Loh MT, et al. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes. The Lancet. 2022;400:1869–1881. DOI: 10.1016/S0140-6736(22)02033-5.
Clinical review and safety screening matter
Retatrutide research is promising, but individual treatment decisions should be based on clinical fit, medication availability, contraindications, medical history, and clinician review. GLP-1-related therapies may not be appropriate for patients with certain thyroid cancer syndromes, pancreatitis history, gallbladder disease, pregnancy status, significant gastrointestinal disease, kidney concerns, diabetes medication risks, or other individual factors.
MyFlowMD begins with intake and physician-guided review before treatment decisions. Results vary, and no medication is guaranteed to produce a specific outcome.
Interested in advanced GLP-1 options?
Start with a free consultation. MyFlowMD can review your goals, medical history, and available options through California telemedicine.
References
- Jastreboff AM, Kaplan LM, Frias JP, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. New England Journal of Medicine. 2023;389:514-526. DOI: 10.1056/NEJMoa2301972.
- Rosenstock J, Frias J, Jastreboff AM, et al. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes. The Lancet. 2023;402:529-544. DOI: 10.1016/S0140-6736(23)01053-X.
- Bajaj HS, Welch M, Shah P, et al. Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1). The Lancet. 2026. DOI: 10.1016/S0140-6736(26)00967-0.
- Sanyal AJ, Kaplan LM, Frias JP, et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nature Medicine. 2024. DOI: 10.1038/s41591-024-03018-2.
- Coskun T, Wu Q, Schloot NC, et al. Effects of retatrutide on body composition in people with type 2 diabetes. The Lancet Diabetes & Endocrinology. 2025;13(8):674–684. DOI: 10.1016/S2213-8587(25)00092-0.
- Urva S, Coskun T, Loh MT, et al. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes. The Lancet. 2022;400:1869–1881. DOI: 10.1016/S0140-6736(22)02033-5.