Company

Eli Lilly

Tirzepatide, retatrutide. Leading dual and triple agonist pipeline in obesity and cardiometabolic.

58 signals

Next earnings: 30 July 2026

Market access

Drug	Indication	Brazil	China	France	Germany	Italy	Japan	Korea	Mexico	Spain	UAE	UK
Trulicity dulaglutide	T2D
Foundayo orforglipron	T2D	-	-	-	-	-	-	-	-	-	-	-
Mounjaro tirzepatide	T2D
Zepbound tirzepatide	obesity	-	-					-	-		-

View full market access tracker

Disease Area

Source

58 of 58 signals

ClinicalTrials20 Apr 2026·Phase 3

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Event-Driven Study to Investigate the Effect of Retatrutide on the Incidence of Major Adverse Cardiovascular Events and Major Adverse Kidney Events in Participants With Body Mass Index ≥27 kg/m2 and Atherosclerotic Cardiovascular Disease and/or Chronic Kidney Disease

Phase 3 cardiovascular and kidney outcomes trial testing retatrutide in adults with BMI ≥27 kg/m² and atherosclerotic cardiovascular disease and/or chronic kidney disease. Enrollment targets 10,000 participants in a double-blind, placebo-controlled, event-driven design running approximately 5 years through February 2029. Eli Lilly advances retatrutide into major outcomes territory, competing directly with established GLP-1 agents that already hold cardiovascular indications like Wegovy and future tirzepatide expansions. This represents the largest cardiovascular outcomes program for any triple agonist to date.

CardiovascularKidneyWeight lossEli Lilly

ClinicalTrials20 Apr 2026·Phase 3

A Phase 3b Study to Investigate the Efficacy and Safety of Different Retatrutide Dose Escalation Schemes in Participants Without Type 2 Diabetes Who Have Obesity or Overweight: A Randomized, Controlled, Double-Blind Trial

Phase 3b trial evaluating different retatrutide dose escalation strategies in adults with obesity or overweight without type 2 diabetes. Target enrollment is 600 participants with approximately 113 weeks study duration in a randomized, double-blind, controlled design. Eli Lilly is testing optimization of their triple agonist dosing in the weight management indication, building on tirzepatide's success in the same population. This represents systematic dose-finding work for retatrutide ahead of potential regulatory filings.

GLP-1Weight lossEli Lilly

ClinicalTrials20 Apr 2026·Phase 3

A Master Protocol to Investigate the Efficacy and Safety of Orforglipron Tablet Once Daily Compared With Placebo in Participants With Obesity or Overweight With and Without Type 2 Diabetes

Phase 3 trial testing orforglipron versus placebo in people with obesity or overweight, with and without type 2 diabetes, measuring HbA1c change as primary endpoint. Enrolling 600 participants with 18-month study duration, part of larger master protocol study. Eli Lilly advances the first approved small-molecule oral GLP-1 into obesity indication, expanding beyond its April 2026 type 2 diabetes approval. This represents a direct challenge to Novo Nordisk's oral semaglutide, which gained FDA approval for obesity in January 2026.

GLP-1Weight lossType 2 diabetesEli Lilly

ClinicalTrials17 Apr 2026·Phase 3● 8/10iHigh impact

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Retatrutide Once Weekly in Participants Who Have Obesity or Overweight and Chronic Low Back Pain

Phase 3 trial evaluating retatrutide for chronic low back pain in people with obesity or overweight, targeting dual primary endpoints of pain intensity reduction and weight loss. 586-person placebo-controlled study expected to complete September 2027, investigating a novel indication beyond traditional metabolic endpoints. Eli Lilly is exploring pain management as a potential expansion for their triple agonist, representing the first major trial of a GLP-1-based therapy specifically for chronic pain conditions.

GLP-1Weight lossOtherEli Lilly

ClinicalTrials17 Apr 2026·Phase 3● 7/10i

A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Once Weekly Eloralintide in Adult Participants With Persistent Obesity or Overweight Treated With a Weekly Incretin, With and Without Type 2 Diabetes

Phase 3 randomized placebo-controlled trial testing once-weekly eloralintide in adults with persistent obesity or overweight on stable incretin therapy, with or without type 2 diabetes. Enrolling 900 participants over 80 weeks, targeting percent change in body weight from baseline. Eli Lilly is exploring combination therapy for people who have insufficient weight loss on existing GLP-1 agents, addressing a growing clinical need as incretin adoption expands. The add-on approach represents a different strategy from Novo Nordisk's CagriSema fixed-dose combination currently in Phase 3.

GLP-1Weight lossDrug comparisonsEli Lilly

ClinicalTrials17 Apr 2026·Phase 3● 8/10iHigh impact

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Event-Driven Study to Investigate the Effect of Orforglipron on the Incidence of Major Adverse Cardiovascular Events in Participants With Established Atherosclerotic Cardiovascular Disease and/or Chronic Kidney Disease

Phase 3 cardiovascular outcomes trial testing orforglipron versus placebo in people with established atherosclerotic cardiovascular disease and/or chronic kidney disease. Event-driven study enrolling 7,140 participants with expected completion in August 2031, approximately 5 years duration. This positions Eli Lilly to compete directly with Novo Nordisk's cardiovascular claims for semaglutide by establishing orforglipron as the first small-molecule oral GLP-1 with proven cardiovascular benefits. The trial targets a high-risk population already established for GLP-1 cardiovascular benefit validation.

GLP-1CardiovascularEli Lilly

ClinicalTrials17 Apr 2026·Phase 3● 8/10iHigh impact

A Phase 3, Open-Label Study of Once Daily LY3502970 Compared With Insulin Glargine in Adult Participants With Type 2 Diabetes and Obesity or Overweight at Increased Cardiovascular Risk

Phase 3 open-label trial compared once-daily oral orforglipron versus insulin glargine in people with type 2 diabetes and obesity or overweight at increased cardiovascular risk. The study enrolled 2,749 participants with primary endpoint of time to first major adverse cardiovascular event, completed in March 2026. Eli Lilly is positioning orforglipron as a cardiovascular outcomes option in high-risk populations, directly competing with established insulin therapy in this indication. This represents the first cardiovascular outcomes trial for orforglipron following its April 2026 FDA approval for type 2 diabetes.

GLP-1Type 2 diabetesWeight lossCardiovascularEli Lilly

PubMed17 Apr 2026·Diabetes, obesity & metabolism● 4/10i

Pharmacokinetic Bioequivalence of Orforglipron Tablets and Capsules in Healthy Participants With Obesity or Overweight.

Orforglipron tablets and capsules demonstrated pharmacokinetic bioequivalence across six dose levels in 429 healthy adults with obesity or overweight. Phase 1, multicenter, open-label study with multiple-dose escalation over 7 days at each dose strength. This establishes formulation flexibility for Eli Lilly's newly approved small-molecule oral GLP-1, potentially supporting manufacturing scale-up and future dose optimization strategies. Safety profiles were similar between formulations with mostly mild adverse events.

GLP-1Type 2 diabetesEli Lilly

PubMed17 Apr 2026·Diabetes, obesity & metabolism● 7/10i

Use of Glucagon-Like Peptide-1 Receptor Agonists and Risk of Parkinson's Disease: Scandinavian Cohort Study.

GLP-1 receptor agonists reduced Parkinson's disease risk by 19% versus sulfonylureas in adults with type 2 diabetes, with incidence rates of 5.2 versus 8.0 per 10,000 person-years. Scandinavian cohort study of 347,026 new users across three countries, with liraglutide accounting for 73% of GLP-1 exposure followed by semaglutide at 13%. This provides the first large-scale evidence for neuroprotective effects beyond weight loss and glycemic control in the GLP-1 class. The observational design cannot establish causation, requiring validation in randomized trials.

GLP-1Brain/NeuroType 2 diabetesNovo Nordisk Eli Lilly

PubMed17 Apr 2026·Annals of internal medicine● 7/10i

Effect of Incretin-Based and Nonpharmacologic Weight Loss on Body Composition : A Systematic Review.

Incretin-based therapies caused muscle-related losses that exceeded expected benchmarks in two-thirds of studies, with a median 34.9% of total weight loss coming from muscle-based tissue rather than the expected 25% threshold. Systematic review of 36 randomized controlled trials with median 71 participants and 26-week duration across liraglutide, semaglutide, tirzepatide, and dulaglutide. This quantifies a clinically important side effect profile that has received limited systematic evaluation despite widespread prescribing of these agents for weight management. The analysis was limited by heterogeneous measurement methods that prevented meta-analysis.

Weight lossGLP-1Side effectsNovo Nordisk Eli Lilly

PubMed17 Apr 2026·Current obesity reports● 5/10i

Metabolic Dysfunction-Associated Steatotic Liver Disease and Respiratory Disorders: A Systematic Review of Clinical and Pathophysiological Associations.

MASLD prevalence was high among people with COPD and obstructive sleep apnea, and was associated with worse respiratory phenotypes, increased exacerbations, and higher respiratory mortality. Systematic review of 22 studies (21 observational, 1 Mendelian randomization) examining MASLD-respiratory disease associations. This establishes MASLD as a marker of systemic metabolic dysfunction that extends beyond liver disease, potentially expanding the addressable patient population for metabolic therapies targeting liver-lung axis crosstalk. Mendelian randomization studies did not consistently support causal relationships except for OSA.

Weight lossLiver/NASHOtherEli Lilly

ClinicalTrials16 Apr 2026·Phase 3● 8/10iHigh impact

A Master Protocol to Investigate the Efficacy and Safety of Orforglipron Tablet Once Daily Compared With Placebo in Participants With Obesity or Overweight With and Without Type 2 Diabetes

Phase 3 master protocol testing oral orforglipron versus placebo in adults with obesity or overweight, with or without type 2 diabetes. Enrolling 1,200 participants across two sub-studies, expected completion August 2027, placebo-controlled design. Eli Lilly advances orforglipron into obesity treatment following its April 2026 FDA approval for type 2 diabetes, representing the first small-molecule oral GLP-1 to enter weight management. This positions Eli Lilly to challenge Novo Nordisk's dominance in oral GLP-1 obesity treatment, where oral semaglutide gained approval in January 2026.

GLP-1Weight lossType 2 diabetesEli Lilly Novo Nordisk

ClinicalTrials16 Apr 2026·Phase 3● 7/10i

A Master Protocol to Investigate the Efficacy and Safety of Orforglipron Tablet Once Daily Compared With Placebo in Participants With Obesity or Overweight With and Without Type 2 Diabetes

Orforglipron, Eli Lilly's oral small-molecule GLP-1 receptor agonist, is being tested against placebo for weight management in people with obesity or overweight without type 2 diabetes. The phase 3 trial targets 600 participants over 18 months, measuring percent change in body weight as the primary endpoint. This represents Eli Lilly's push to expand orforglipron beyond its April 2026 FDA approval for type 2 diabetes into the weight management market, competing directly with Novo Nordisk's approved oral semaglutide for obesity. The trial is part of a broader master protocol evaluating orforglipron across multiple obesity-related populations.

GLP-1Weight lossEli Lilly

PubMed16 Apr 2026·Diabetes, obesity & metabolism● 7/10i

Cardiometabolic Profiles of Oral and Subcutaneous Glucagon-Like Peptide-1 Receptor Mono-Agonists in Adults With Overweight or Obesity: A Systematic Review and Network Meta-Analysis.

Semaglutide 7.2 mg achieved the highest cardiometabolic efficacy index (0.86), followed by orforglipron 36 mg (0.68) and semaglutide 2.4 mg (0.66), all producing placebo-adjusted weight reductions ≥10%. Network meta-analysis of 19 RCTs with 13,117 adults with overweight or obesity, evaluating composite outcomes across seven cardiometabolic parameters. This provides the first head-to-head comparison of oral orforglipron against both approved and investigational semaglutide doses across multiple cardiometabolic endpoints, with orforglipron showing competitive performance despite being the first small-molecule oral GLP-1.

GLP-1Weight lossDrug comparisonsEli Lilly Novo Nordisk

PubMed15 Apr 2026·Diabetes, obesity & metabolism● 5/10i

GLP-1, GIP, and Glucagon Excursions During a Mixed Meal Tolerance Test in Young and Lean South Asians Versus Europids.

South Asian adults showed biphasic glucose response to meals versus monophasic response in European adults, with sex-specific differences in GLP-1, GIP, and glucagon patterns despite similar BMI. Mixed meal tolerance test in 49 young, lean adults (24 South Asian, 25 European) over 240 minutes. This represents first detailed comparison of incretin hormone responses between these populations, revealing distinct metabolic phenotypes that could affect GLP-1 therapy responses. The findings suggest South Asians may need different dosing strategies or combination approaches for optimal glycemic control.

GLP-1Type 2 diabetesMechanismsEli Lilly

PubMed14 Apr 2026·Circulation● 7/10iPick of the week

Risk of Heart Failure Hospitalization for GLP-1 Receptor Agonists Versus DPP-4 Inhibitors or SGLT-2 Inhibitors in Patients With Type 2 Diabetes: A Target Trial Emulation.

GLP-1 receptor agonists reduced heart failure hospitalization risk by 23% versus DPP-4 inhibitors (HR 0.77) but matched SGLT-2 inhibitors (HR 1.02) in adults with type 2 diabetes. Target trial emulation of Swedish health records, 63,083 patients across two comparisons, 3-year follow-up. This provides the first direct head-to-head comparison of GLP-1RAs versus SGLT-2 inhibitors for heart failure prevention, confirming cardiovascular benefits extend beyond major adverse events to heart failure hospitalization.

GLP-1SGLT2Type 2 diabetesCardiovascularReal-world evidenceNovo Nordisk Eli Lilly

PubMed14 Apr 2026·Annals of internal medicine● 5/10i

Endocrinology: What You May Have Missed in 2025.

A review of 9 key endocrinology studies from 2025 examined treatment intensification strategies, emerging side effects of GLP-1 receptor agonists, and comparative safety data across diabetes and obesity therapies. Narrative review synthesizing published research from multiple clinical trials and observational studies. The compilation provides the first comprehensive assessment of GLP-1RA side effect concerns including nonarteritic anterior ischemic optic neuropathy alongside head-to-head comparisons of dulaglutide dose escalation versus tirzepatide switching. Limited by being a narrative review rather than systematic analysis of primary endpoints.

GLP-1SGLT2Type 2 diabetesSide effectsDrug comparisonsEli Lilly Novo Nordisk

ClinicalTrials14 Apr 2026·Phase 3● 7/10i

A Phase III, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Once-Weekly RO7795068 Administered to Participants With Obesity or Overweight and Type 2 Diabetes

RO7795068, a dual GLP-1/GIP receptor agonist from Roche, is being tested versus placebo for weight management in people with obesity or overweight and type 2 diabetes. Phase 3 trial targets 1,600 participants over 72 weeks in a randomized, double-blind, placebo-controlled design. This positions Roche to compete directly with Eli Lilly's tirzepatide (Mounjaro/Zepbound) in the dual incretin mechanism space across both diabetes and obesity indications. The trial represents Roche's first major entry into the competitive GLP-1 obesity market dominated by Novo Nordisk and Eli Lilly.

GLP-1Weight lossType 2 diabetesDrug comparisonsHoffmann-La Roche Eli Lilly

PubMed13 Apr 2026·Diabetes care● 4/10i

Clinical Potential of GIP in Type 2 Diabetes and Obesity.

Tirzepatide's dual GLP-1 and GIP receptor targeting represents the most effective incretin therapy for adults with type 2 diabetes and obesity. Narrative review exploring incretin biology and GIPR mechanisms. This analysis positions GIP receptor activity as a key differentiator driving tirzepatide's superior efficacy, potentially informing next-generation dual agonist development. The relative contribution of GIP versus GLP-1 receptor engagement in tirzepatide's effects remains unestablished.

GLP-1Type 2 diabetesWeight lossEli Lilly

ClinicalTrials13 Apr 2026·Phase 3● 8/10iHigh impact

A Phase 3, Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of Retatrutide Compared to Tirzepatide in Adults Who Have Obesity

Eli Lilly is conducting a Phase 3 head-to-head trial comparing retatrutide versus tirzepatide in adults with obesity. The double-blind study targets 800 participants over 89 weeks with primary endpoint of percent body weight change, completing December 2026. This represents the first direct comparison between Eli Lilly's next-generation triple receptor agonist retatrutide and its approved dual agonist tirzepatide in obesity. The trial positions Eli Lilly to potentially establish superiority claims for retatrutide ahead of expected regulatory submissions.

GLP-1Weight lossDrug comparisonsEli Lilly

ClinicalTrials13 Apr 2026·Phase 3● 8/10iHigh impact

A Master Protocol to Investigate the Efficacy and Safety of LY3437943 Once Weekly in Participants With Type 2 Diabetes Mellitus Who Have Obesity or Overweight: A Randomized Double-Blind, Placebo-Controlled Trial

Phase 3 trial evaluating retatrutide once weekly in adults with type 2 diabetes who have obesity or overweight, including a subset with obstructive sleep apnea. Enrolling 1,000 participants across 89 weeks with completion expected May 2026, measuring weight reduction and sleep apnea improvement versus placebo. Eli Lilly advances retatrutide into dual indication territory, competing directly with Novo Nordisk's semaglutide and their own tirzepatide in the expanding cardiometabolic space. The inclusion of sleep apnea patients follows Zepbound's December 2024 OSA approval, positioning retatrutide for multiple obesity comorbidities.

GLP-1Weight lossType 2 diabetesEli Lilly Novo Nordisk

ClinicalTrials13 Apr 2026·Phase 3● 7/10i

A Phase 3, Randomized, Multicenter, Open-label Study to Investigate the Efficacy and Safety of Retatrutide Once Weekly Compared With Semaglutide Once Weekly in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Metformin With or Without SGLT2 Inhibitor (TRANSCEND-T2D-2)

Phase 3 open-label trial comparing retatrutide with semaglutide in adults with type 2 diabetes inadequately controlled on metformin with or without SGLT2 inhibitor. The study enrolls 1,250 participants over 26 months, targeting HbA1c reduction as the primary endpoint, with completion expected August 2026. Eli Lilly positions retatrutide as a direct competitor to semaglutide in the core type 2 diabetes market, testing their triple-receptor agonist against the current GLP-1 standard. The head-to-head design provides comparative evidence needed for formulary positioning and prescriber confidence.

GLP-1Type 2 diabetesDrug comparisonsEli Lilly Novo Nordisk

PubMed13 Apr 2026·Diabetes care● 6/10i

Hepatic Events Prevention by Antihyperglycemic Therapies and Intervention Comparisons in Type 2 Diabetes: The HEPATIC-T2DM Network Meta-analysis.

GLP-1 receptor agonists showed the lowest risk of hepatic decompensation versus all other diabetes drug classes (HRs 0.16-0.91), while thiazolidinediones had the lowest hepatocellular carcinoma risk and SGLT2 inhibitors the lowest cirrhosis risk. Network meta-analysis of 46 observational studies including 7.1 million adults with type 2 diabetes. This provides the first comprehensive liver safety ranking across all major diabetes drug classes, potentially informing prescribing in patients with existing liver disease risk. All evidence is observational, limiting causal conclusions.

GLP-1SGLT2Type 2 diabetesLiver/NASHDrug comparisonsNovo Nordisk Eli Lilly

ClinicalTrials8 Apr 2026·Phase 3● 8/10iHigh impact

Efficacy and Safety of Co-administered Cagrilintide and Semaglutide (CagriSema) 2.4 mg/2.4 mg s.c. Once Weekly Versus Tirzepatide 15 mg s.c. Once Weekly in Participants With Type 2 Diabetes Inadequately Controlled on Metformin With or Without an SGLT2 Inhibitor

Phase 3 head-to-head trial compares CagriSema (dual cagrilintide and semaglutide) 2.4/2.4 mg against tirzepatide 15 mg weekly in adults with type 2 diabetes inadequately controlled on metformin with or without SGLT2 inhibitors. The randomized trial enrolled 1,000 participants with primary endpoints of HbA1c and weight change, completing in March 2026. This represents Novo Nordisk's direct challenge to Eli Lilly's tirzepatide dominance with a novel dual-agonist combination targeting both GLP-1 and amylin receptors. The head-to-head design positions CagriSema for potential differentiation in the competitive dual-agonist space.

GLP-1Type 2 diabetesDrug comparisonsNovo Nordisk Eli Lilly

ClinicalTrials8 Apr 2026·Phase 3● 8/10iHigh impact

Efficacy and Safety of Co-administered Cagrilintide and Semaglutide (CagriSema) 1.0 mg/1.0 mg s.c. Once Weekly Versus Tirzepatide 5 mg s.c. Once Weekly in Participants With Type 2 Diabetes Inadequately Controlled on Metformin, SGLT2 Inhibitor or Both

Phase 3 trial compares CagriSema (cagrilintide + semaglutide combination) 1.0 mg weekly versus tirzepatide 5 mg weekly in 1,023 adults with type 2 diabetes inadequately controlled on metformin, SGLT2 inhibitor, or both. Active comparator design with 68-week duration, completion expected June 2026. This represents Novo Nordisk's direct challenge to Eli Lilly's tirzepatide dominance, testing whether dual amylin/GLP-1 combination can match dual GIP/GLP-1 efficacy in the core type 2 diabetes market. Head-to-head positioning against tirzepatide's lowest approved dose could support differentiated commercial messaging if CagriSema demonstrates superiority.

GLP-1Type 2 diabetesDrug comparisonsNovo Nordisk Eli Lilly

PubMed7 Apr 2026·Diabetes, obesity & metabolism● 6/10i

Real-World Clinical Evidence of Tirzepatide for Metabolic Abnormalities in Subjects With Type 2 Diabetes: The Multicenter Retrospective Observational Hokkaido-TZP Study.

Tirzepatide reduced HbA1c by 1.07% and body weight by 3.1 kg over 6 months in adults with type 2 diabetes in Japanese real-world practice. Multicenter retrospective observational study of 828 patients treated for 6+ months across 10 centers in Hokkaido. The efficacy remained consistent even in patients switching from existing incretin-based medications, providing first real-world evidence of tirzepatide's effectiveness after GLP-1 failure. Discontinuation rate was 5.4% due to adverse events or other clinical reasons.

GLP-1Type 2 diabetesReal-world evidenceEli Lilly Novo Nordisk

PubMed5 Apr 2026·Obesity (Silver Spring, Md.)● 7/10i

Weight Loss With GLP-1 Agonists in Nondiabetic Adults: Systematic Review and Network Meta-Analysis.

Tirzepatide provides greater weight loss than semaglutide or liraglutide in adults with obesity without diabetes, with maximum tolerated doses achieving the largest reductions followed by tirzepatide 15mg, 10mg, semaglutide 2.4mg, tirzepatide 5mg, and liraglutide 3mg. Network meta-analysis of 15 RCTs, 14,059 patients. This is the first head-to-head comparison across all three FDA-approved obesity medications in adults without diabetes, establishing tirzepatide's superiority over existing GLP-1 options.

GLP-1Weight lossDrug comparisonsEli Lilly Novo Nordisk

PubMed2 Apr 2026·The New England journal of medicine● 6/10i

GLP-1 Receptor Agonists.

GLP-1 receptor agonists reduce cardiovascular risk and slow renal failure progression in high-risk patients with type 2 diabetes through large-scale randomized controlled trials. Review article in NEJM summarizing established mechanisms and clinical benefits. Confirms cardiovascular and kidney benefits already incorporated into current prescribing guidelines and reimbursement decisions. Highlights ongoing concerns about muscle and bone mass loss as potential long-term safety considerations.

GLP-1Type 2 diabetesWeight lossCardiovascularKidneySide effectsNovo Nordisk Eli Lilly

PubMed1 Apr 2026·Obesity science & practice● 5/10i

Targeting Multiple Gut-Brain Pathways in Obesity: Rationale for Combination Pharmacotherapy.

Gut hormone analogs (GLP-1s like semaglutide, tirzepatide) and naltrexone-bupropion combination target different brain pathways in obesity treatment, creating mechanistic rationale for combination therapy. Narrative review synthesizing existing evidence on gut-brain axis mechanisms. This establishes the scientific foundation for combining GLP-1 receptor agonists with naltrexone-bupropion in patients with inadequate response to monotherapy.

GLP-1Weight lossMechanismsNovo Nordisk Eli Lilly

PubMed1 Apr 2026·Diabetes, obesity & metabolism● 4/10i

Effect of empagliflozin on urinary albumin excretion and hypoxic biomarkers in early diabetic kidney disease: A randomised double-blind, placebo-controlled trial.

Empagliflozin showed a declining trend in albumin creatinine ratio versus placebo but failed to reach statistical significance at 24 weeks in adults with type 2 diabetes and microalbuminuria. Randomized controlled trial of 79 patients over 24 weeks comparing empagliflozin 10mg daily to placebo. This provides new mechanistic insight into SGLT2 inhibitor kidney protection through suppression of hypoxia-induced angiogenic factors VEGF and ANGPTL2, offering biological explanation for established renal benefits. The primary endpoint missed statistical significance despite early positive trends.

SGLT2Type 2 diabetesKidneyBoehringer Ingelheim Eli Lilly

PubMed1 Apr 2026·Obesity (Silver Spring, Md.)● 7/10i

Comparative Efficacy of Metabolic/Bariatric Surgery Versus GLP-1 Receptor Agonists: A Network Meta-Analysis of Randomized Controlled Trials.

Metabolic/bariatric surgery produces 10.3% greater total weight loss than GLP-1 receptor agonists at under 2 years, with the gap narrowing but persisting at longer follow-up. Network meta-analysis of 30 RCTs, 20,015 patients. This provides the first head-to-head comparison across all available GLP-1 therapies versus surgery, confirming surgery's superiority while positioning tirzepatide as the closest non-surgical alternative. Comparisons were indirect through lifestyle intervention as common comparator.

GLP-1Weight lossEli Lilly

PubMed1 Apr 2026·Diabetes, obesity & metabolism● 5/10i

Tirzepatide on physical function in adults with overweight or obesity: A systematic review and meta-analysis.

Tirzepatide 10-15mg weekly improved patient-reported physical function by 2.26 points on SF-36 and 10.10 points on IWQOL-Lite-CT versus placebo in adults with overweight or obesity. Meta-analysis of 6 RCTs, 4,531 participants, moderate evidence quality. This provides the first systematic evidence that GLP-1/GIP dual agonists enhance physical capacity beyond weight loss, addressing a key quality-of-life endpoint for payer discussions. Extremely high heterogeneity between studies (I2 = 99.8%) limits confidence in the pooled estimates.

GLP-1Weight lossEli Lilly

PubMed1 Apr 2026·Obesity (Silver Spring, Md.)● 7/10i

Disparities in Prescription of Long-Acting GLP-1s.

Black and Hispanic patients with obesity were 49% and 47% less likely to receive semaglutide or tirzepatide compared to White patients, disparities that largely disappeared after Massachusetts Medicaid expanded coverage. Retrospective analysis of 2,060 patients at a tertiary care center, January and April 2024. This provides the first evidence that state Medicaid coverage policy directly eliminates racial prescribing disparities for GLP-1 medications. Analysis limited to single health system in Massachusetts.

GLP-1Pricing/accessNovo Nordisk Eli Lilly

PubMed1 Apr 2026·Diabetes, obesity & metabolism● 6/10i

A treat-to-target approach for obesity management: A post hoc analysis of the SURMOUNT-5 trial.

About 23-34% of patients with obesity treated with tirzepatide and 14-21% treated with semaglutide reached proposed treat-to-target thresholds for waist-to-height ratio or BMI reduction. Post hoc analysis of SURMOUNT-5 trial, 751 patients, 72 weeks. This provides the first structured target framework for obesity treatment goals, moving beyond simple weight loss percentages to defined metabolic risk thresholds. The analysis was post hoc rather than a prespecified endpoint.

GLP-1Weight lossDrug comparisonsEli Lilly Novo Nordisk

PubMed1 Apr 2026·Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery● 7/10i

Cardiovascular outcomes and mortality of bariatric surgery versus glucagon-like peptide-1 receptor agonists: a systematic review and meta-analysis.

Bariatric surgery reduced mortality by 43%, major cardiovascular events by 35%, and heart failure by 55% compared to GLP-1 receptor agonists in adults with obesity. Meta-analysis of 5 observational cohorts, 39,569 patients. This provides the first head-to-head comparison of these major obesity treatments on hard cardiovascular outcomes, showing substantial advantages for surgery. Observational design limits causal inference due to potential confounding and selection bias.

GLP-1CardiovascularWeight lossNovo Nordisk Eli Lilly

PubMed1 Apr 2026·International journal of obesity (2005)● 6/10i

Efficacy of GLP-1 analog peptides, semaglutide, tirzepatide, and retatrutide on MC4R deficient obesity and their comparison.

Tirzepatide achieved 31.6% weight reduction versus 19.7% for semaglutide and 24.1% for retatrutide in MC4R knockout mice, a model of severe genetic obesity. Preclinical study, 21-day treatment duration in mice deficient in melanocortin pathways. This provides the first head-to-head comparison of major GLP-1 therapies in severe genetic obesity, suggesting these agents work through MC4R-independent mechanisms.

GLP-1Weight lossDrug comparisonsEli Lilly Novo Nordisk

PubMed1 Apr 2026·Diabetes, obesity & metabolism● 6/10i

GLP-1 receptor agonists and cardiovascular outcomes in Asian, Black or African American, and White populations: An updated meta-analysis including the SOUL trial.

GLP-1 receptor agonists reduced cardiovascular risk by 27% in Asian populations versus 14% in White populations, with similar but non-significant effects in Black or African American populations. Meta-analysis of 9 trials including 74,703 participants with type 2 diabetes or overweight/obesity. This provides the first robust evidence of differential GLP-1RA cardiovascular benefits across racial groups, with Asian populations showing significantly greater relative risk reduction. The finding emerges from inclusion of the recent SOUL trial data.

GLP-1CardiovascularNovo Nordisk Eli Lilly

PubMed1 Apr 2026·Diabetes, obesity & metabolism● 5/10i

Effect of lixisenatide on arterial stiffness in people with type 2 diabetes and kidney disease: Results of a randomised controlled trial.

Lixisenatide showed no effect on aortic pulse wave velocity, a cardiovascular risk marker, in adults with type 2 diabetes and chronic kidney disease after 24 weeks versus placebo. Randomized controlled trial of 90 patients, 24 weeks, double-blind design with placebo control. This provides mechanistic insight into why short-acting GLP-1 receptor agonists like lixisenatide showed neutral cardiovascular outcomes in trials while longer-acting agents demonstrated benefits. The study was limited to a single center with modest sample size.

GLP-1CardiovascularKidneyType 2 diabetesSanofi Novo Nordisk Eli Lilly

FDA1 Apr 2026·New Drug Approval (NDA/BLA)● 10/10iHigh impact

FDA Approves Foundayo (Orforglipron) — New Drug Approval (NDA/BLA)

FDA approved orforglipron (Foundayo, Eli Lilly) for type 2 diabetes -- a once-daily oral small-molecule GLP-1 receptor agonist. Orforglipron is the first non-peptide oral GLP-1 approved in the US; oral semaglutide (Rybelsus, Novo Nordisk) has been approved for T2D since 2019 and expanded to obesity in January 2026. Unlike Rybelsus, orforglipron requires no fasting or water volume restrictions before dosing.

GLP-1Type 2 diabetesPricing/accessEli Lilly Novo Nordisk

FDA1 Apr 2026·FDA Press Release● 8/10iHigh impact

FDA Approves First New Molecular Entity Under National Priority Voucher Program

FDA approved Foundayo (orforglipron) on April 1, 2026, marking the fifth approval under the Commissioner's National Priority Voucher pilot program. This represents approval of the first small-molecule oral GLP-1 receptor agonist, distinct from the peptide-based oral semaglutide (Rybelsus) approved by FDA in 2019. Eli Lilly gains competitive positioning in the oral GLP-1 space with a differentiated mechanism that requires no fasting restrictions. The approval leverages FDA's expedited voucher pathway designed to incentivize development of treatments addressing unmet medical needs.

GLP-1Type 2 diabetesEli Lilly

PubMed31 Mar 2026·Journal of the American College of Cardiology● 6/10i

Obesity and Heart Failure With Reduced Ejection Fraction: A Review.

Most patients with heart failure with reduced ejection fraction have overweight or obesity, but weight loss interventions remain unexplored in this population despite proven safety and efficacy in heart failure with preserved ejection fraction. This JACC review synthesizes existing evidence across multiple studies. The analysis reveals a critical research gap as no novel obesity pharmacotherapies are currently being evaluated specifically in patients with HFrEF, despite mechanistic rationale suggesting potential benefit.

GLP-1Weight lossCardiovascularNovo Nordisk Eli Lilly

PubMed30 Mar 2026·BMJ open diabetes research & care● 6/10i

Safety and efficacy of switching from dulaglutide to tirzepatide across clinically relevant baseline characteristics in participants with T2D: subgroup analysis of SURPASS-SWITCH.

Switching from dulaglutide to tirzepatide provided superior HbA1c reduction (greater in high baseline HbA1c, low BMI) and weight loss (greater in non-Hispanic populations) across all patient subgroups at 40 weeks. Phase IV RCT, open-label, active-controlled, adults with type 2 diabetes on stable dulaglutide for 6+ months. This is the first head-to-head switching study between GLP-1 agents, establishing tirzepatide's superiority over Novo's dulaglutide across diverse patient populations.

GLP-1Type 2 diabetesDrug comparisonsEli Lilly Novo Nordisk

PubMed28 Mar 2026·JAMA cardiology● 8/10iHigh impact

Cardiorenal Outcomes With Tirzepatide Compared With Dulaglutide in Patients With Diabetes and Cardiovascular Disease: A Post Hoc Analysis of the SURPASS-CVOT Randomized Clinical Trial.

Tirzepatide reduced a 6-component cardiorenal composite endpoint by 16% versus dulaglutide (23.7% vs 27.4%, HR 0.84) in people with type 2 diabetes and cardiovascular disease. Post hoc analysis of SURPASS-CVOT double-blind RCT, 13,165 patients, median 46.9 months follow-up. This provides the first head-to-head cardiorenal comparison between tirzepatide and a GLP-1 agonist in high-risk cardiovascular patients, extending beyond the primary non-inferiority finding. Gastrointestinal adverse events were higher with tirzepatide (42.5% vs 35.9%).

GLP-1CardiovascularKidneyType 2 diabetesDrug comparisonsEli Lilly Novo Nordisk

ClinicalTrials24 Mar 2026·Phase 3● 7/10i

A Master Protocol to Investigate the Efficacy and Safety of Orforglipron Once Daily in Participants With Hypertension and Obesity or Overweight: Randomized, Double-Blind, Placebo-Controlled Trials (ATTAIN-HYPERTENSION)

Phase 3 master protocol evaluates once-daily orforglipron for hypertension treatment in people with obesity or overweight across two independent studies. The placebo-controlled framework targets 974 participants with completion expected September 2027. Eli Lilly is expanding orforglipron beyond its approved type 2 diabetes indication, testing the first small-molecule oral GLP-1 in cardiovascular indication territory dominated by Novo Nordisk's Wegovy. This represents a direct challenge to semaglutide's expanding label into cardiometabolic conditions.

GLP-1CardiovascularWeight lossEli Lilly

PubMed23 Mar 2026·Diabetes, obesity & metabolism● 8/10iHigh impact

GLP-1 Receptor/Dual Agonists for Weight Loss: A Systematic Review and Network Meta-Analysis of RCTs.

Tirzepatide achieved 7.17-fold greater likelihood of ≥5% weight loss versus placebo in adults with type 2 diabetes, outperforming subcutaneous semaglutide (4.74-fold) and oral semaglutide (2.85-fold). Network meta-analysis of 127 RCTs, 58,976 participants across seven GLP-1 receptor agonists. This provides the first comprehensive head-to-head comparison showing tirzepatide's superior weight loss efficacy across both diabetes and non-diabetes populations. Higher nausea and vomiting rates occurred with tirzepatide versus semaglutide formulations.

GLP-1Weight lossType 2 diabetesDrug comparisonsEli Lilly Novo Nordisk

PubMed21 Mar 2026·Lancet (London, England)● 8/10iHigh impact

Efficacy and safety of once-daily oral orforglipron compared with oral semaglutide in adults with type 2 diabetes (ACHIEVE-3): a multinational, multicentre, non-inferiority, open-label, randomised, phase 3 trial.

Orforglipron 12 mg and 36 mg achieved superior HbA1c reduction versus oral semaglutide 7 mg and 14 mg, with treatment differences ranging from -0.24% to -0.68%. Phase 3 RCT with 1,698 adults with type 2 diabetes inadequately controlled on metformin, 52-week duration, head-to-head comparison. This provides the first head-to-head data showing an oral non-peptide GLP-1 receptor agonist outperforming oral semaglutide in glycemic control. Higher gastrointestinal side effects and discontinuation rates with orforglipron (9-10% vs 4-5%) may limit uptake despite superior efficacy.

GLP-1Type 2 diabetesDrug comparisonsEli Lilly Novo Nordisk

ClinicalTrials20 Mar 2026·Phase 3● 6/10i

A Phase 3 Study to Investigate the Efficacy and Safety of Orforglipron Once Daily in Participants Who Have Obesity or Overweight and Osteoarthritis of the Knee: A Multicenter, Randomized, Double-Blind, Parallel-Arm, Placebo-Controlled Trial

Phase 3 trial evaluating orforglipron once daily in people with obesity or overweight and osteoarthritis of the knee. The study targets 800 participants over 74 weeks in a placebo-controlled design, measuring pain reduction via the WOMAC Pain Subscale. This represents Eli Lilly's push to expand orforglipron beyond type 2 diabetes into new indications where GLP-1s show promise. The trial combines weight loss with joint pain relief, targeting a large patient population not directly addressed by current obesity medications.

GLP-1Weight lossEli Lilly

ClinicalTrials20 Mar 2026·Phase 3● 7/10i

A Master Protocol to Investigate the Efficacy and Safety of Orforglipron Tablet Once Daily Compared With Placebo in Female Participants With Stress Urinary Incontinence Who Have Obesity or Overweight

Orforglipron is being tested in women with stress urinary incontinence who have obesity or overweight in two phase 3 studies under a master protocol. The trials will enroll 1,000 participants with 58-week follow-up, comparing daily oral orforglipron to placebo. This represents a novel indication expansion for Eli Lilly's small-molecule GLP-1 beyond diabetes and weight management, targeting a large underserved population where weight loss could provide therapeutic benefit. This marks the first major GLP-1 trial in urological conditions, potentially opening a new market segment.

GLP-1OtherEli Lilly

ClinicalTrials19 Mar 2026·Phase 3● 9/10iHigh impact

Efficacy and Safety of Tirzepatide Once Weekly in Participants Without Type 2 Diabetes Who Have Obesity or Are Overweight With Weight-Related Comorbidities: A Randomized, Double-Blind, Placebo-Controlled Trial (SURMOUNT-1)

Phase 3 SURMOUNT-1 tests once-weekly tirzepatide at three doses versus placebo in adults without type 2 diabetes who have obesity or are overweight with comorbidities. The randomized, double-blind trial targets 2,539 participants with primary efficacy assessment at 72 weeks. This represents tirzepatide's pivotal obesity trial against placebo, potentially supporting Eli Lilly's bid to compete directly with Wegovy in the non-diabetic obesity market. A prediabetes subgroup continues long-term to assess diabetes prevention.

Weight lossGLP-1Eli Lilly

FDA19 Mar 2026·Supplemental Approval — Efficacy● 6/10i

FDA Approves Wegovy (Semaglutide) — Supplemental Approval — Efficacy

FDA approved a supplemental efficacy application for Wegovy (semaglutide, Novo Nordisk) on March 19, 2026. This represents a label expansion for the already-approved obesity drug, adding new efficacy data or indication refinements to the existing NDA. Novo Nordisk continues to strengthen Wegovy's competitive position in the obesity market against Eli Lilly's Zepbound through additional clinical evidence.

GLP-1Weight lossNovo Nordisk Eli Lilly

ClinicalTrials3 Mar 2026·Phase 3● 7/10i

A Phase 3b, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Retatrutide Treatment in the Maintenance of Weight Reduction in Individuals With Obesity

Phase 3b trial evaluates retatrutide's ability to maintain weight loss in people with obesity through an 80-week open-label lead-in followed by 36-week randomized withdrawal to placebo or continued treatment. The study enrolls 643 participants with completion expected in April 2028, testing two retatrutide doses against placebo switch. This addresses a critical commercial question for Eli Lilly: whether people can maintain weight loss after achieving it, a key payer concern for obesity drugs. The withdrawal design mirrors successful maintenance studies that supported Wegovy's market access positioning.

Weight lossGLP-1Eli Lilly

ClinicalTrials17 Feb 2026·Phase 3● 8/10iHigh impact

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Evaluating the Efficacy and Safety of Tirzepatide Once Weekly Compared to Placebo in Adult Participants With Type 1 Diabetes and Obesity or Overweight

Phase 3 trial evaluating tirzepatide once weekly versus placebo in 905 adults with type 1 diabetes and obesity or overweight, measuring HbA1c change as primary endpoint. Double-blind, placebo-controlled study expected to complete November 2026, currently active but not recruiting. Eli Lilly is testing tirzepatide in type 1 diabetes, a population where GLP-1 agonists have limited evidence and where weight management remains an unmet need alongside glycemic control. This represents expansion into a new diabetes indication where insulin remains the cornerstone therapy.

GLP-1Type 1 diabetesWeight lossEli Lilly

ClinicalTrials12 Jan 2026·Phase 3● 8/10iHigh impact

A Phase 3, Randomized, Double-blind, Placebo-Controlled Study to Investigate the Effect of Tirzepatide on the Reduction of Morbidity and Mortality in Adults With Obesity

Phase 3 cardiovascular outcomes trial testing tirzepatide versus placebo in 15,374 adults with obesity, measuring time to first major adverse cardiovascular event (death, MI, stroke, coronary revascularization, or heart failure). The randomized, double-blind, placebo-controlled study completed enrollment with expected results in October 2027. This represents Eli Lilly's bid to establish tirzepatide's cardiovascular benefits in obesity, directly competing with Novo Nordisk's Wegovy which gained MACE indication approval in March 2024. The massive enrollment suggests Lilly is positioning for a broad obesity cardiovascular claim to differentiate from Novo's narrower obesity plus established CVD indication.

GLP-1Weight lossCardiovascularEli Lilly Novo Nordisk

ClinicalTrials12 Dec 2025·Phase 3● 8/10iHigh impact

Efficacy and Safety of Cagrilintide s.c. in Combination With Semaglutide s.c. (CagriSema s.c.) Once Weekly for Weight Management and Long-term Weight Maintenance in Participants With Obesity

Novo Nordisk is testing CagriSema (cagrilintide plus semaglutide combination) against placebo in 609 people with obesity across a 3-year phase 3 trial for weight management and long-term maintenance. The study includes a main phase followed by an extension where all participants receive active treatment at different doses. This represents Novo's dual-hormone strategy to extend beyond single GLP-1 therapy, competing directly with Eli Lilly's tirzepatide franchise in obesity. The 3-year duration targets the critical question of sustained weight loss that regulators and payers prioritize.

Weight lossGLP-1Novo Nordisk Eli Lilly

ClinicalTrials5 Nov 2025·Phase 3● 8/10iHigh impact

A Phase 3, Randomized, Double-Blind Study to Investigate the Efficacy and Safety of Once-Daily Oral Orforglipron Compared With Placebo in Adult Participants With Obesity or Overweight With Weight-Related Comorbidities (ATTAIN-1)

ATTAIN-1 is testing orforglipron, Eli Lilly's oral small-molecule GLP-1 receptor agonist, versus placebo in 3,127 adults with obesity or overweight with weight-related comorbidities. This 72-week phase 3 trial with 2-year extension for people with prediabetes is placebo-controlled and has completed enrollment. Eli Lilly is building the clinical foundation for orforglipron in obesity, following its April 2026 FDA approval for type 2 diabetes where it differentiated from Novo Nordisk's oral semaglutide with no dosing restrictions. This represents Eli Lilly's entry into oral GLP-1 obesity treatment, directly challenging Novo Nordisk's pending high-dose oral semaglutide for obesity approved in January 2026.

GLP-1Weight lossEli Lilly Novo Nordisk

ClinicalTrials29 Sept 2025·Phase 3● 6/10i

A Master Protocol to Investigate the Efficacy and Safety of Orforglipron Once Daily in Participants Who Have Obstructive Sleep Apnea and Obesity or Overweight: A Randomized, Double-Blind, Placebo-Controlled Trial

Eli Lilly is testing orforglipron, its oral small-molecule GLP-1, in adults with moderate-to-severe obstructive sleep apnea and obesity or overweight across two parallel studies. The phase 3 master protocol will enroll 600 participants through November 2026, comparing orforglipron to placebo with sleep apnea severity as the primary endpoint. This represents Eli Lilly's move into sleep medicine with orforglipron, targeting an indication where Zepbound recently gained FDA approval in December 2024. The dual-study design separates participants by PAP therapy use, suggesting potential for differentiated positioning across OSA treatment patterns.

GLP-1Weight lossOtherEli Lilly

ClinicalTrials23 Jul 2025·Phase 3● 8/10iHigh impact

A Randomized, Double-Blind, Phase 3 Study to Investigate the Efficacy and Safety of LY3437943 Once Weekly Compared to Placebo in Participants With Severe Obesity and Established Cardiovascular Disease

Phase 3 randomized, double-blind, placebo-controlled study evaluates retatrutide once weekly in people with severe obesity and established cardiovascular disease. The trial targets 1,800 participants over 113 weeks, with primary endpoint of percent change in body weight from baseline. Eli Lilly is advancing retatrutide, a triple agonist (GLP-1/GIP/glucagon), into a high-risk cardiovascular population that represents a significant commercial opportunity beyond standard obesity treatment. This positions retatrutide as a potential competitor to Wegovy, which gained cardiovascular risk reduction approval in March 2024 for people with obesity and established CVD.

Weight lossCardiovascularGLP-1Eli Lilly

ClinicalTrials18 Apr 2025·Phase 3● 8/10iHigh impact

A Master Protocol to Investigate the Efficacy and Safety of LY3437943 Once Weekly in Participants Without Type 2 Diabetes Who Have Obesity or Overweight: A Randomized, Double-Blind, Placebo-Controlled Trial (TRIUMPH-1)

TRIUMPH-1 is a Phase 3 master protocol testing retatrutide (Eli Lilly's triple agonist) in 2,300 people with obesity or overweight without type 2 diabetes, including subsets with knee osteoarthritis and obstructive sleep apnea. The 89-week double-blind, placebo-controlled trial with optional 24-week extension measures weight change, osteoarthritis pain scores, and sleep apnea severity. Eli Lilly is positioning retatrutide across multiple obesity-related conditions beyond weight management, directly competing with Novo Nordisk's Wegovy in the obesity market. This comprehensive approach targets three distinct indications within one protocol, reflecting Lilly's strategy to establish retatrutide as a multi-indication obesity therapy.

Weight lossCardiovascularEli Lilly Novo Nordisk