Orforglipron: A Non-Peptide Oral GLP-1 Receptor Agonist in Clinical Development

This content is provided by Superpower Health for educational and informational purposes only. Superpower Health does not prescribe, sell, or facilitate access to orforglipron. Orforglipron is an investigational medication not yet FDA-approved for human use. It is not available through Superpower or by prescription; access is limited to clinical trial enrollment. This page is not a substitute for medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider.

GLP-1 receptor agonists have transformed obesity and diabetes pharmacotherapy over the past decade. But every compound in that class until recently shared a structural limitation: they are peptides. Peptides are digested in the gastrointestinal tract, which is why semaglutide and tirzepatide are injected, and why the oral form of semaglutide (Rybelsus) requires fasted administration with only a small sip of water to bypass the digestive environment. The question researchers began asking was whether a small molecule could activate the same receptor without any of those delivery constraints.

Orforglipron is Eli Lilly's answer to that question. It is the most clinically advanced oral non-peptide GLP-1 receptor agonist in development, with Phase 3 data now published across four trials. This article covers how orforglipron works, why its chemistry differs from oral semaglutide, what the ATTAIN and ACHIEVE trial programs have found, and what the regulatory timeline looks like as of April 2026.

Key Takeaways

• Regulatory Status: Not FDA-approved as of April 2026. The ATTAIN Phase 3 obesity program and ACHIEVE-1 Phase 3 type 2 diabetes trial have published results. An NDA submission was anticipated for 2025 with a potential approval decision in 2026. Superpower does not offer orforglipron.
• Research Stage: Phase 3 complete (ATTAIN-1: 72-week obesity trial; ATTAIN-2: 72-week obesity with type 2 diabetes trial; ACHIEVE-1: 40-week early type 2 diabetes trial). Phase 2 data published in The New England Journal of Medicine in 2023 and The Lancet in 2023.
• Availability: Not available by prescription in the United States. Access limited to clinical trial enrollment. Superpower does not offer this compound. For current trial information, see ClinicalTrials.gov.
• Prescribing information: View compound reference data (PubChem CID 162538677)
• How it works: Activates the GLP-1 receptor via non-peptide small-molecule binding, stimulating insulin secretion, suppressing glucagon, and reducing appetite without requiring injection or fasted dosing.
• What the research shows: In the ATTAIN-1 Phase 3 trial, orforglipron 36 mg produced 11.2% mean weight loss at 72 weeks versus 2.1% for placebo in adults with obesity without type 2 diabetes. In ACHIEVE-1, it reduced HbA1c by up to 1.48 percentage points versus 0.41 for placebo at 40 weeks in early type 2 diabetes.

What Is Orforglipron?

Orforglipron (development name LY3502970) is a once-daily oral non-peptide glucagon-like peptide-1 (GLP-1) receptor agonist developed by Eli Lilly and Company. Unlike semaglutide, tirzepatide, and all other GLP-1 receptor agonists currently approved or in late-stage development, orforglipron is not a peptide: it is a synthetic small molecule. This structural distinction determines nearly every practical difference between orforglipron and its drug-class predecessors, beginning with how it is absorbed and how it can be taken.

As of April 2026, orforglipron is investigational only. It has not received FDA approval for any indication. The compound is not available through commercial pharmacies, compounding pharmacies, or telehealth providers. Access is limited to enrollment in registered clinical trials.

How Orforglipron Works

GLP-1 receptor agonism: the shared mechanism

GLP-1 (glucagon-like peptide-1) is an incretin hormone secreted by L-cells in the small intestine following meals. Its receptor, the GLP-1 receptor, is expressed in pancreatic beta cells, the hypothalamus, the brainstem, the stomach, and several other tissues. When the receptor is activated, it signals through cyclic AMP (cAMP) to stimulate glucose-dependent insulin secretion, suppress glucagon release, slow gastric emptying, and engage hypothalamic circuits that reduce appetite and food intake. This combination of effects drives both glycemic control and weight reduction. GLP-1 receptor agonists like semaglutide and tirzepatide produce their metabolic effects by persistently activating this receptor at supraphysiological levels, maintaining the signaling that native GLP-1 produces only transiently after meals. The canonical synthesis of this receptor biology is a 2018 review by Drucker in Cell Metabolism, which covers cAMP-mediated insulin secretion, glucagon suppression, delayed gastric emptying, and central satiety signaling in a single reference that remains the authoritative background for any explanation of how GLP-1 agonism produces its metabolic effects.

Why orforglipron's small-molecule structure matters

The central challenge of oral GLP-1 agonism is that peptides are digested in the stomach and small intestine before they can reach systemic circulation. Native GLP-1 has a plasma half-life of approximately two minutes. Semaglutide, engineered with fatty acid conjugation and albumin binding, has a half-life long enough for once-weekly injection, but the peptide backbone still requires a specialized delivery strategy for oral use. Oral semaglutide (Rybelsus) uses a co-formulation with SNAC (sodium N-[8-(2-hydroxybenzoyl) aminocaprylate]), an absorption enhancer that protects semaglutide from gastric degradation and enables transcellular stomach absorption. This mechanism was characterized by Buckley and colleagues in a study published in Science Translational Medicine in 2018 and reviewed in the context of oral GLP-1 drug development by Bucheit and colleagues in a 2020 paper in Diabetes Technology and Therapeutics. A 2022 review by Aroda and colleagues in Reviews in Endocrine and Metabolic Disorders further documented why peptide-based oral GLP-1 therapies require fasted dosing and absorption-enhancer co-formulation, setting up the contrast with orforglipron's small-molecule simplicity. The mechanism works, but it comes with a pharmacological constraint: the SNAC-enabled window of absorption is narrow, which is why Rybelsus must be taken on an empty stomach with only up to 4 oz of water, followed by a 30-minute wait before food or other medications. Missing this protocol substantially reduces bioavailability.

Orforglipron sidesteps the problem entirely. As a small molecule, it does not have a peptide backbone to digest. It does not require an absorption enhancer. It does not require fasted administration. The pharmacological characterization of this non-peptide binding mode was established by Sloop and colleagues at Eli Lilly in a study published in Science Translational Medicine in 2024, which described orforglipron's high-affinity GLP-1 receptor binding, its distinct intracellular signaling profile relative to peptide agonists, and the finding that low receptor occupancy by orforglipron is sufficient to yield a full biological response. Phase 1a pharmacokinetic data published by Pratt and colleagues in Diabetes, Obesity and Metabolism in 2023 confirmed an extended half-life of approximately 24 to 68 hours across the dose range studied, dose-proportional pharmacokinetics, and the feasibility of once-daily dosing without food or water restrictions. A subsequent Phase 1b multiple-ascending-dose study in adults with type 2 diabetes, published by Pratt and colleagues in Diabetes, Obesity and Metabolism in 2024, further confirmed that orforglipron could be dosed once daily without food or water restrictions while maintaining glycemic effect, supporting the unrestricted-dosing framing that distinguishes it from oral semaglutide.

Orforglipron versus oral semaglutide: the practical difference

Both orforglipron and oral semaglutide (Rybelsus) activate the GLP-1 receptor. Their mechanisms of entry into the body are fundamentally different, with direct downstream implications for how patients take them. Oral semaglutide requires fasted administration, a 30-minute post-dose waiting period before eating or drinking, and strict adherence to this protocol for each dose. Orforglipron has none of these requirements. It can be taken with or without food. This distinction is not cosmetic: in a class defined by its weekly injectable competitors, the real-world adherence advantage of a pill with no dosing constraints is substantial. A 2025 retrospective cohort study by Rodriguez and colleagues published in JAMA Network Open found that one-year discontinuation among adults using injectable GLP-1 receptor agonists was 64.8% in patients without type 2 diabetes and 46.5% in those with type 2 diabetes, highlighting how difficult adherence is even with effective agents. The logistical simplicity of an unrestricted daily pill may translate to meaningfully better real-world persistence, though that hypothesis requires prospective data to confirm.

What the Phase 2 and Phase 3 Trials Show

Phase 2 obesity readout: 36 weeks, 272 participants

The foundational Phase 2 efficacy data in obesity comes from a 36-week randomized, double-blind, placebo-controlled trial published in The New England Journal of Medicine in 2023 by Wharton and colleagues. That study enrolled 272 adults with obesity or overweight plus at least one weight-related condition, without type 2 diabetes, and randomized them to four orforglipron doses (12, 24, 36, or 45 mg once daily) or placebo for 36 weeks. At the highest dose, participants achieved a mean body weight reduction of 14.7% from baseline versus 2.3% for placebo by week 36. Weight reductions across the four dose groups ranged from 9.4% to 14.7%. Between 46% and 75% of orforglipron participants achieved at least 10% weight reduction by week 36, compared to 9% on placebo. Gastrointestinal adverse events were the most common side effects, rated mild to moderate in the majority of participants, and occurring predominantly during the dose-escalation phase; 10% to 17% of orforglipron participants discontinued due to adverse events versus 2% on placebo. These findings established orforglipron as capable of producing weight loss in the range of injectable GLP-1 class agents, from a once-daily pill with no dosing constraints.

Phase 2 type 2 diabetes readout: glycemic and weight outcomes

A concurrent Phase 2 dose-response trial in type 2 diabetes was published in The Lancet in 2023 by Frias and colleagues. The study tested orforglipron doses of 3, 12, 24, 36, and 45 mg once daily versus both placebo and dulaglutide 1.5 mg once weekly (an approved injectable GLP-1 receptor agonist) in adults with type 2 diabetes. At the highest dose, orforglipron reduced HbA1c by up to 2.10 percentage points versus 0.43 for placebo and 1.10 for dulaglutide at 26 weeks, with body weight reductions reaching up to 10.1 kg compared to 2.2 kg for placebo and 3.9 kg for dulaglutide. Doses of 12 mg and above produced statistically significant and clinically meaningful glycemic improvements relative to dulaglutide, the injectable comparator. Gastrointestinal adverse events were reported in 44% to 70% of orforglipron recipients versus 18% of placebo recipients, consistent with the known pharmacological effects of GLP-1 receptor agonism. This cross-trial comparison between orforglipron and an injectable GLP-1 agent must be interpreted with attention to differences in study design, patient populations, and dose selection; it is provided here for scientific context only, as these are different agents with different regulatory statuses.

ACHIEVE-1: Phase 3 in early type 2 diabetes

The first published Phase 3 confirmatory trial is ACHIEVE-1, a 40-week randomized controlled trial conducted in adults with early-stage type 2 diabetes managed through diet and exercise alone, with baseline HbA1c between 7.0% and 9.5%. Published in The New England Journal of Medicine in 2025 by Rosenstock and colleagues, the trial randomized 559 participants across three orforglipron doses (3 mg, 12 mg, and 36 mg) and placebo. All three orforglipron doses produced statistically superior HbA1c reductions versus placebo, with reductions of 1.24, 1.47, and 1.48 percentage points respectively versus 0.41 for placebo. Weight loss increased with dose, ranging from 4.5% to 7.6% versus 1.7% for placebo. The most common adverse events were mild to moderate gastrointestinal symptoms; no severe hypoglycemia was reported. ACHIEVE-1 represents the first Phase 3 confirmation of orforglipron's glycemic efficacy and provides the pivotal T2D dataset for the regulatory submission.

ATTAIN-1: Phase 3 obesity without type 2 diabetes

ATTAIN-1 is the key Phase 3 obesity trial in adults without type 2 diabetes. Published in The New England Journal of Medicine in 2025, the trial randomized 3,127 adults with obesity across three orforglipron dose groups (6 mg, 12 mg, and 36 mg) and placebo over 72 weeks. At the highest dose (36 mg), participants achieved mean body weight reduction of 11.2% at 72 weeks versus 2.1% for placebo. At this dose, 54.6% of participants achieved at least 10% weight loss, 36.0% achieved at least 15%, and 18.4% achieved at least 20%. Secondary cardiometabolic endpoints, including waist circumference, systolic blood pressure, triglycerides, and non-HDL cholesterol, all improved significantly relative to placebo. Adverse events were predominantly gastrointestinal and mild to moderate in severity. ATTAIN-1 is the primary obesity efficacy anchor for orforglipron's FDA submission.

ATTAIN-2: Phase 3 obesity with type 2 diabetes

ATTAIN-2 extended the Phase 3 program to adults with both obesity and type 2 diabetes. Published in The Lancet in 2025, the 72-week trial enrolled 1,613 participants across 136 sites in ten countries and randomized them to orforglipron doses of 6 mg, 12 mg, or 36 mg versus placebo. At the 36 mg dose, participants achieved 9.6% mean body weight reduction versus 2.5% for placebo, with statistically significant improvements across lipid, glycemic, and blood pressure endpoints. The safety profile was consistent with other GLP-1 receptor agonists, with mild to moderate gastrointestinal adverse events occurring predominantly during dose escalation and discontinuation rates of 6.1% to 9.9% for orforglipron versus 4.1% for placebo. Taken together with ATTAIN-1, the ATTAIN program demonstrates consistent Phase 3 efficacy across the full obesity population spectrum, with and without comorbid type 2 diabetes.

Beyond Weight Loss: Broader Metabolic and Cardiovascular Context

Weight and HbA1c are the primary endpoints in orforglipron's Phase 3 program, but they are not the only metabolic variables the compound and its class affect. A 2025 pooled analysis by Wharton and colleagues in Cardiovascular Diabetology reported that orforglipron improved cardiometabolic biomarkers across lipids, blood pressure, and inflammation in adults with type 2 diabetes and obesity, supporting the case that its benefits extend beyond weight. At the class level, the SELECT trial, published in 2023 by Lincoff and colleagues in the New England Journal of Medicine, demonstrated that subcutaneous semaglutide 2.4 mg reduced major adverse cardiovascular events by 20 percent in 17,604 adults with obesity and pre-existing cardiovascular disease but without diabetes, establishing the first hard-outcome evidence that GLP-1 receptor agonism can reduce cardiovascular events. A dedicated cardiovascular outcomes trial for orforglipron is ongoing; the class-level data do not yet confirm that orforglipron produces comparable event reduction, but they frame the scientific hypothesis that its ongoing CVOT program is designed to test. The liver is another tissue where the class has accumulated evidence: a 2022 systematic review by Mantovani, Byrne, and Targher in The Lancet Gastroenterology and Hepatology pooled 25 RCTs across 2,597 adults (mean age 52, mean BMI 32 kg/m², 62% with type 2 diabetes) and reported that GLP-1 receptor agonists — predominantly liraglutide and semaglutide across 10 GLP-1 RCTs — improved individual NASH histological features (steatosis, hepatocyte ballooning, lobular inflammation) and achieved NASH resolution without worsening of fibrosis, supporting a class-level hepatic effect. This evidence is generated with peptide GLP-1 agonists; whether orforglipron, as a structurally distinct small molecule, produces equivalent histological benefit has not been tested. No specific orforglipron hepatotoxicity signal has emerged in the published Phase 1, Phase 2, or Phase 3 data to date.

How Orforglipron Compares to the GLP-1 Class

Weight loss magnitude compared to injectable agents

The benchmark for injectable GLP-1 receptor agonist weight loss in obesity is the STEP 1 trial, published in The New England Journal of Medicine in 2021 by Wilding and colleagues. In STEP 1, once-weekly subcutaneous semaglutide 2.4 mg produced a mean weight loss of 14.9% at 68 weeks versus 2.4% for placebo in 1,961 adults with obesity. Orforglipron's ATTAIN-1 result of 11.2% at 72 weeks with the 36 mg dose is numerically lower than the STEP 1 semaglutide result. This cross-trial comparison carries important caveats: the two trials had different study designs, dose escalation schedules, populations, and durations, and cross-trial comparisons are unreliable for these reasons. Orforglipron and injectable semaglutide have fundamentally different regulatory statuses and evidence bases; this comparison is provided for scientific context only and does not imply equivalence. The relevant question for the pill-versus-injection decision is not which produces more weight loss at the highest Phase 3 dose in a controlled trial, but which achieves better outcomes in real-world settings where adherence, access, and logistics shape actual results.

The needle-free adherence hypothesis

Injection avoidance is consistently cited as a barrier to GLP-1 therapy initiation and persistence across patient populations. The 2022 American Gastroenterological Association clinical practice guideline on pharmacological interventions for adults with obesity, published in Gastroenterology by Grunvald and colleagues, strongly recommended pharmacotherapy in addition to lifestyle intervention for adults with BMI of 30 or above who have not achieved adequate response to lifestyle changes alone, establishing guidelines-based demand for effective oral options. If a once-daily pill without dosing restrictions achieves 11% weight loss in Phase 3, the clinical value proposition for populations who decline injectable therapy is substantial. Whether orforglipron actually converts higher adherence into comparable or superior real-world outcomes relative to weekly injections is a question that post-approval observational data will need to answer.

Orforglipron versus danuglipron

Orforglipron is not the only oral small-molecule GLP-1 receptor agonist that has been tested in clinical trials. Pfizer developed danuglipron, a twice-daily oral non-peptide GLP-1 receptor agonist. The Phase 1 proof-of-concept work by Saxena and colleagues, a randomized, placebo-controlled, multiple-ascending-dose phase 1 trial in 98 adults with type 2 diabetes on background metformin over 28 days, published in Nature Medicine in 2021, demonstrated dose-dependent reductions in fasting plasma glucose and body weight with mostly mild adverse events (predominantly nausea, dyspepsia, and vomiting), establishing the feasibility of small-molecule GLP-1 receptor agonism in humans and setting the stage for the broader class. A 2025 Phase 2b obesity trial by Buckeridge and colleagues in Diabetes, Obesity and Metabolism (n = 626 randomized; danuglipron 40–200 mg twice daily over 26 or 32 weeks) reported statistically significant placebo-corrected weight reductions ranging from approximately 5.0% to 12.9%, but only 39.3% of participants completed treatment, with approximately 38% discontinuing due to adverse events — predominantly nausea and vomiting — and Pfizer subsequently halted the danuglipron obesity program in 2024. A 2023 systematic review and meta-analysis by Karakasis and colleagues in Metabolism pooled 7 RCTs of orforglipron and danuglipron (n = 1,037), reporting a mean HbA1c reduction of −1.03 percentage points vs control in adults with type 2 diabetes (95% CI −1.29 to −0.77; p < 0.001), a −3.26 kg weight reduction in T2D (95% CI −4.79 to −1.72; p < 0.001) and a −7.52 kg reduction in adults with obesity (95% CI −14.63 to −0.41; p = 0.038). Gastrointestinal adverse events were significantly increased (OR 2.57; p < 0.001), as were AE-driven discontinuations (OR 2.89; p = 0.016), with neutral effects on severe hypoglycaemia (OR 0.34; p = 0.11) and serious adverse events (OR 0.95; p = 0.91). The wide weight-loss confidence interval in obesity reflects a small and heterogeneous obesity evidence base at the time of the meta-analysis. Orforglipron's once-daily dosing schedule and its Phase 3 tolerability data, showing predominantly mild to moderate gastrointestinal events with manageable discontinuation rates, differentiate it from the danuglipron experience, though the compounds cannot be directly compared without head-to-head trial data. The discontinuation of danuglipron does not imply that the oral small-molecule GLP-1 class as a whole has a tolerability ceiling; it suggests that compound-specific pharmacological properties matter within the class. A 2025 systematic review in Pharmacological Reviews by Kokkorakis and colleagues situated both orforglipron and danuglipron within the broader pipeline of emerging obesity pharmacotherapies, including incretin analogs and small-molecule GLP-1 receptor agonists in development.

Side Effects and Tolerability

The side effect profile of orforglipron across Phase 2 and Phase 3 trials is consistent with the established pharmacology of GLP-1 receptor agonism. The following is drawn from clinical trial data; it is not a complete list of potential adverse effects, and individual experiences vary. A licensed provider will evaluate your specific clinical situation before any prescribing decision. A 2025 network meta-analysis by Ismaiel and colleagues in International Journal of Obesity quantified the gastrointestinal adverse-event profile across GLP-1 receptor agonists in non-diabetic adults with obesity, providing an honest reference point for how orforglipron's tolerability compares to other agents in the class.

Common (reported in Phase 2 and Phase 3 studies):

• Nausea: the most frequently reported adverse event, typically mild to moderate, occurring most often during dose escalation
• Vomiting: reported across dose groups, generally self-limited
• Diarrhea: consistent with GLP-1 receptor agonist class effects on gastric motility
• Constipation: less common than nausea and vomiting but reported across trials
• Decreased appetite: pharmacologically expected given GLP-1 receptor agonism of hypothalamic satiety circuits

Less common but reported:

• Treatment discontinuation due to adverse events: occurred in 10% to 17% of participants in the Phase 2 obesity trial at the highest doses; 6.1% to 9.9% in ATTAIN-2; rates varied by dose and trial across the Phase 3 program
• Abdominal pain and discomfort: reported in a minority of participants, generally during dose escalation
• Elevated liver enzymes: long-term hepatic safety data beyond Phase 3 trial durations is not yet available

No severe hypoglycemia was reported in ACHIEVE-1, consistent with the glucose-dependent mechanism of GLP-1 receptor agonism: insulin secretion is stimulated only when glucose levels are elevated, which reduces hypoglycemia risk compared to insulin or sulfonylurea therapy. As an investigational compound, orforglipron's complete long-term safety profile has not been established.

Who Orforglipron Is Being Studied For

The ATTAIN and ACHIEVE clinical trial programs define the populations in which orforglipron's efficacy and safety have been evaluated. Based on these designs:

• Adults with obesity (BMI of 30 or above) or overweight (BMI of 27 or above) with at least one weight-related condition, without type 2 diabetes (ATTAIN-1 and the 2023 Phase 2 obesity trial)
• Adults with obesity or overweight and comorbid type 2 diabetes (ATTAIN-2)
• Adults with early-stage type 2 diabetes not yet requiring pharmacotherapy beyond lifestyle intervention (ACHIEVE-1)

The compound is not studied or approved for type 1 diabetes. Individuals who declined injectable GLP-1 therapy due to needle aversion or dosing complexity represent the population whose potential benefit from an oral unrestricted pill is theoretically highest, but this hypothesis has not been tested prospectively in head-to-head enrollment studies.

Regulatory Status and Timeline

As of April 2026, orforglipron is not FDA-approved for any indication. It is an investigational drug available only within registered clinical trial settings. The compound is not available through commercial pharmacies, specialty pharmacies, or compounding pharmacies in the United States. No prescription pathway exists outside of clinical trial enrollment.

Eli Lilly has publicly indicated that FDA submission for orforglipron was anticipated in 2025, with a potential review and approval decision possible in 2026, contingent on the completeness of the regulatory submission and the FDA review timeline. Regulatory approval is not guaranteed. The Phase 3 program supporting the submission includes ACHIEVE-1 (T2D), ATTAIN-1 (obesity without T2D), and ATTAIN-2 (obesity with T2D); additional trials evaluating cardiovascular outcomes and other endpoints are ongoing as of April 2026. Orforglipron is not listed on the WADA Prohibited List as of April 2026; athletes subject to anti-doping testing should confirm current status with their governing body before any participation in clinical trials involving this compound.

For individuals interested in trial participation, current enrollment information is maintained at ClinicalTrials.gov. Superpower does not facilitate clinical trial enrollment.

Understanding Your Metabolic Baseline

Orforglipron's mechanism operates across multiple metabolic systems simultaneously: insulin secretion, glucagon suppression, gastric emptying, lipid metabolism, and body weight regulation. For anyone considering participation in a clinical trial or simply seeking to understand where their own metabolic health stands, the biomarkers that orforglipron's Phase 3 trials tracked as primary and secondary endpoints provide a useful map of what matters:

• Hemoglobin A1c (HbA1c): The primary glycemic endpoint in all orforglipron diabetes trials. HbA1c reflects average blood glucose over approximately three months and is the clinical benchmark for type 2 diabetes management. Baseline HbA1c determines whether and how elevated blood sugar is affecting metabolic health before any intervention is considered.
• Fasting glucose: A direct measure of blood sugar in the fasted state. Used alongside HbA1c to characterize glycemic control and assess insulin sensitivity. Tracked across all orforglipron trials as a secondary endpoint.
• Fasting insulin: Elevated fasting insulin, in the context of normal or elevated glucose, indicates insulin resistance: the pancreas is producing more insulin to maintain glycemic control. Understanding baseline insulin sensitivity is relevant for anyone in the metabolic risk categories that orforglipron targets.
• Triglycerides: A secondary cardiometabolic endpoint in the ATTAIN trials. GLP-1 receptor agonism is associated with triglyceride reductions, likely through reduced hepatic VLDL production and improved insulin sensitivity. Baseline triglycerides characterize cardiovascular risk and metabolic health independent of weight.
• LDL cholesterol: Tracked as a secondary endpoint across Phase 3. Weight loss from GLP-1 therapy is associated with modest LDL improvements; baseline lipid status is essential context for understanding cardiometabolic risk.
• HDL cholesterol: Tracked alongside LDL across the ATTAIN program. Low HDL is a component of metabolic syndrome and an independent cardiovascular risk factor. Establishing baseline HDL provides a reference point for tracking how metabolic health changes over time.
• High-sensitivity CRP (hs-CRP): A marker of systemic inflammation. GLP-1 receptor agonists have been associated with reductions in inflammatory markers in some analyses. Baseline hs-CRP captures the inflammatory component of metabolic disease that weight and glucose measures alone may not fully characterize.

Knowing your metabolic baseline is not conditional on access to an investigational drug. The biomarkers associated with metabolic health and weight are measurable now, regardless of what treatments are or are not available to you. Superpower's approach to preventive health starts with comprehensive biomarker testing, because objective data is the prerequisite for any informed clinical decision.

IMPORTANT SAFETY INFORMATION

Orforglipron (LY3502970) is NOT FDA-approved for any indication. As of April 2026, it is an investigational new drug evaluated in clinical trials only. It is not a Category 2 bulk drug substance and has no legal compounding pathway. It is not available through commercial pharmacies, compounding pharmacies, specialty pharmacies, or telehealth prescribing services in the United States. Orforglipron has completed Phase 2 and Phase 3 trials in obesity and type 2 diabetes; Phase 3 results have been published, and an NDA submission was anticipated in 2025. As of April 2026, no NDA approval has been granted. Superpower is a technology platform; Superpower does not prescribe, sell, compound, or facilitate access to orforglipron.

Do not use orforglipron if you: have a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2); have a history of pancreatitis; have severe gastroparesis or other significant gastrointestinal motility disorders; are pregnant, may become pregnant, or are breastfeeding (safety in pregnancy has not been established); have type 1 diabetes (not studied); are under 18 years of age (pediatric safety not established); have severe renal or hepatic impairment (not studied); or have known hypersensitivity to orforglipron or any formulation component.

Warnings (class-level GLP-1 receptor agonist considerations, extrapolated from approved GLP-1 agonist labeling): class-associated preclinical finding of thyroid C-cell tumors in rodents at clinically relevant exposures; class-associated signals for acute pancreatitis, acute gallbladder disease, and hypoglycemia (particularly when used with insulin or sulfonylureas); gastroparesis exacerbation; possible dehydration-induced acute kidney injury secondary to severe GI symptoms; potential delayed gastric emptying with implications for perioperative aspiration risk. Whether these class-level signals apply to orforglipron specifically will be addressed in the FDA-approved labeling upon approval, if granted.

Common side effects reported in Phase 2 and Phase 3 clinical trials: nausea, vomiting, diarrhea, constipation, decreased appetite, abdominal pain, dyspepsia, eructation. These were predominantly mild to moderate in severity and most frequent during dose escalation phases. Treatment discontinuation due to adverse events ranged from approximately 6% to 17% across trials and dose levels.

Long-term data limitations: Cardiovascular outcomes, long-term thyroid safety, pancreatitis incidence beyond trial durations, and effects in special populations (renal and hepatic impairment, pregnancy, pediatrics) have not been fully characterized in completed trials. The long-term durability of weight loss and the extent of weight regain after discontinuation have not been established in peer-reviewed publications as of April 2026.

Compound reference: PubChem CID 162538677. No FDA-approved prescribing information exists; upon approval, DailyMed will carry the authoritative label. For current trial enrollment, visit ClinicalTrials.gov. This is not a complete list of risks.

Additional Questions

How does orforglipron compare to semaglutide for weight loss?

In the STEP 1 trial, injectable semaglutide 2.4 mg produced mean weight loss of 14.9% at 68 weeks. Orforglipron's highest Phase 3 dose produced 11.2% at 72 weeks in ATTAIN-1. These two figures come from different trials with different designs, populations, and dose escalation schedules; direct comparison is unreliable. Orforglipron and semaglutide also have fundamentally different regulatory statuses: semaglutide is FDA-approved, orforglipron is investigational. This comparison is for scientific context only.

Can I get orforglipron without a prescription?

No. Orforglipron is not available by prescription or over the counter. As of April 2026, it is accessible only through registered clinical trial enrollment. No commercial, compounding, or telehealth pathway exists for orforglipron. Superpower does not offer this compound.

What is the ATTAIN program?

ATTAIN is the Phase 3 obesity clinical trial program for orforglipron. It includes ATTAIN-1 (72 weeks in adults with obesity without type 2 diabetes; 3,127 participants) and ATTAIN-2 (72 weeks in adults with obesity and type 2 diabetes; 1,613 participants). Both trials have published results as of 2025. A separate Phase 3 program, ACHIEVE, evaluated orforglipron in type 2 diabetes; ACHIEVE-1 was published in 2025.