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Foundayo ™ (orforglipron) tablet
0.8 mg / 2.5 mg / 5.5 mg / 9 mg / 14.5 mg / 17.2 mg
This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.
How do you switch patients from other glucagon-like peptide-1 receptor agonist (GLP-1 RA) medications to Foundayo™ (orforglipron)?
Lilly cannot recommend how to switch from other GLP-1 RA medications to orforglipron. Data from ATTAIN-MAINTAIN are described in this response. Healthcare providers should determine the best course for each patient when considering medication changes.
See important safety information, including boxed warning, in the attached prescribing information.
Content Overview
General Considerations Before Switching Patients to Orforglipron From Other GLP-1 RA Medications
General Considerations Before Switching Patients to Orforglipron From Other GLP-1 RA Medications
The orforglipron US Prescribing Information does not include recommendations on switching from other glucagon-like peptide-1 receptor agonist (GLP-1 RA) medications to orforglipron.1
Eli Lilly and Company cannot provide information on
- how to switch a patient from other GLP-1 RA medications to orforglipron
- dose equivalence between other GLP-1 RA medications and orforglipron, or
- washout periods between discontinuing another GLP‑1 RA and initiating orforglipron.
The healthcare practitioner should consider the potential risks and benefits of treatment options and monitor them appropriately.
The ATTAIN-MAINTAIN study evaluated the use of orforglipron for weight maintenance after an initial treatment with injectable semaglutide (1.7 mg or 2.4 mg) or tirzepatide (10 mg or 15 mg).2
ATTAIN-MAINTAIN evaluated a specific switching scenario that may not represent clinical practice scenarios. This study does not allow general conclusions on how to switch from other GLP-1 RA medications to orforglipron. Data from ATTAIN-MAINTAIN are described in this response.
Eli Lilly and Company has not evaluated the efficacy and safety of orforglipron following treatment with GLP-1 RA medications other than injectable semaglutide and tirzepatide. No studies have evaluated the use of orforglipron following oral semaglutide.
Follow the orforglipron starting dosage and escalation described in the US prescribing information to reduce the risk of gastrointestinal adverse reactions.1
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How Were Participants Switched from Injectable Semaglutide or Tirzepatide to Orforglipron in ATTAIN‑MAINTAIN?
This response presents efficacy and safety data from the investigational orforglipron capsule formulation (1 mg, 3 mg, 6 mg, 12 mg, 24 mg, and 36 mg) shown as equivalent doses of once-daily orforglipron tablets (0.8 mg, 2.5 mg, 5.5 mg, 9 mg, 14.5 mg, and 17.2 mg) approved in the United States.1-3
ATTAIN-MAINTAIN was a 52-week, phase 3b, randomized, double-blind, placebo-controlled trial comparing the efficacy and safety of once-daily orforglipron versus placebo for maintenance of body weight reduction in adults with obesity, or overweight with weight-related comorbidities who previously completed the SURMOUNT-5 head-to-head trial.2
Please refer to the Appendix for a SURMOUNT-5 study overview.
Participants in ATTAIN-MAINTAIN switched from a maximum tolerated dose (MTD) of injectable semaglutide (1.7 mg or 2.4 mg) or tirzepatide (10 mg or 15 mg) to a 9 mg dose of oral orforglipron, which was then increased every 4 weeks until reaching 17.2 mg or MTD (14.5 mg or 17.2 mg).2,3
What Was the Study Design of ATTAIN-MAINTAIN?
The ATTAIN-MAINTAIN trial was conducted at 29 sites in the United States. The study examined 2 separate cohorts based on their prior treatment in SURMOUNT-5, including
- tirzepatide MTD 10 mg or 15 mg (cohort 1), or
- semaglutide MTD 1.7 mg or 2.4 mg (cohort 2).2
Both cohorts were analyzed independently.2
In the SURMOUNT-5 trial, participants with obesity or overweight and without type 2 diabetes (T2D) were randomized to receive tirzepatide or semaglutide for 72 weeks. After completion of SURMOUNT-5, eligible participants were provided the option to enroll in the ATTAIN-MAINTAIN trial.2,4
The ATTAIN-MAINTAIN trial included
- a screening period of up to 2 weeks (after completion of SURMOUNT-5)
- a 52-week treatment period, and
- a safety follow-up of 2 weeks.2
Following randomization, participants were initiated on blinded orforglipron 9 mg or matching placebo once daily, in a 3:2 ratio, with initiation occurring ideally within 14 days of last dose of study treatment in SURMOUNT-5. The orforglipron dose was increased every 4 weeks until 17.2 mg or MTD (14.5 mg or 17.2 mg) was reached, which was then maintained for the remainder of the 52-week study. Starting at week 24, rescue therapy with orforglipron was initiated for participants in the placebo group who regained ≥50% of the weight lost during SURMOUNT-5.2,3
All participants received lifestyle counseling on healthy diet and physical activity.2
ATTAIN-MAINTAIN Study Design provides a schematic representation of the study design for ATTAIN-MAINTAIN.
Figure 1 description: SURMOUNT-5 was a 72-week study that evaluated the efficacy and safety of tirzepatide vs injectable semaglutide in participants with obesity or overweight with obesity-related complications, without type 2 diabetes. Participants were randomized in a 1:1 ratio to receive tirzepatide or semaglutide as an adjunct to a reduced calorie diet and increased physical activity. Participants who completed SURMOUNT-5 were eligible to enroll in ATTAIN-MAINTAIN. ATTAIN-MAINTAIN was a 52-week, randomized, double blind, placebo-controlled trial that evaluated the efficacy and safety of orforglipron in the maintenance of body weight reduction. Participants previously treated with tirzepatide in SURMOUNT-5 were enrolled in cohort 1, and participants previously treated with semaglutide were enrolled in cohort 2; the cohorts were analyzed independently. The ATTAIN-MAINTAIN trial included a screening period of up to 2 weeks following completion of SURMOUNT 5, a 52-week treatment period, and a 2-week safety follow up. Participants were randomized in a 3:2 ratio to receive blinded orforglipron or placebo once daily. Orforglipron was initiated at 9 mg, and the dose was increased every 4 weeks until reaching 17.2 mg or MTD (14.5 mg or 17.2 mg). All participants were instructed to maintain a healthy diet and physical activity throughout the ATTAIN MAINTAIN treatment period.
Abbreviations: MTD = maximum tolerated dose; OFG = orforglipron; PBO = placebo; QD = once daily; Sema = semaglutide; TZP = tirzepatide.
What Were the Key Inclusion and Exclusion Criteria in ATTAIN-MAINTAIN?
Key inclusion and exclusion criteria for the ATTAIN-MAINTAIN study are presented in Key Inclusion and Exclusion Criteria in ATTAIN-MAINTAIN.
Key Inclusion Criteria |
Key Exclusion Criteria |
|
|
Abbreviations: BMI = body mass index; MEN2 = multiple endocrine neoplasia type 2; MTC = medullary thyroid cancer; T1D = type 1 diabetes; T2D = type 2 diabetes.
aParticipants with a history of gestational diabetes were eligible to participate in ATTAIN-MAINTAIN.
bParticipants were eligible if the following procedures were performed >1 year before visit 1: liposuction, abdominoplasty, or cryolipolysis.
cExcept for use of injectable tirzepatide or semaglutide treatment provided by the SURMOUNT-5 study.
What Were the Key Primary and Secondary Endpoints in ATTAIN-MAINTAIN?
For both cohorts, the primary endpoint was the percent maintenance of body weight reduction in SURMOUNT-5 for participants who achieved a body weight plateau (ie, <5% body weight change from weeks 60 to 72 in the SURMOUNT-5 study).2
For each participant, this value was calculated by dividing the total weight loss achieved between the start of SURMOUNT-5 and the end of ATTAIN-MAINTAIN (week 52) by the total weight loss achieved between the start of SURMOUNT-5 and the baseline of ATTAIN-MAINTAIN (week 0).2
Key secondary endpoints were
- assessment (yes/no) of maintaining at least 80% of body weight reduction (in plateau participants)
- percent change in body weight from SURMOUNT-5 baseline (all participants), and
- percent maintenance of body weight reduction (all participants).2
What Were the Baseline Demographics and Clinical Characteristics of Participants in ATTAIN-MAINTAIN?
The ATTAIN-MAINTAIN study enrolled 376 participants across 2 cohorts.2
In cohort 1 (tirzepatide group from SURMOUNT-5),
- mean age was 48.5 years
- 62.9% of the participants were female
- 73.8% of the participants were white, and
- mean body weight was 90.1 kg.2
In cohort 2 (semaglutide group from SURMOUNT-5),
- mean age was 48.6 years
- 68.4% of the participants were female
- 75.9% of the participants were white, and
- mean body weight was 94.4 kg.2
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Discontinuations
In ATTAIN-MAINTAIN, the most common reasons for treatment discontinuation were
- withdrawal by participant, and
- adverse events.2
What Are the Efficacy Results From ATTAIN-MAINTAIN?
Two statistical estimands, the modified treatment-regimen and efficacy estimand, were used to evaluate efficacy data in ATTAIN-MAINTAIN.2
The modified treatment-regimen estimand represents treatment effect regardless of treatment discontinuation or initiation of prohibited medications. This estimand also assumes that participants who had bariatric surgery or another weight loss procedure or took rescue orforglipron would not have received any additional improvement from their randomized study treatment.2
The efficacy estimand represents treatment effect that participants had stayed on treatment, had not taken prohibited medications, had not had bariatric surgery or any other weight management procedures and assuming that participants who took rescue orforglipron would not have received any additional improvement from their randomized study treatment.2
What Is the Efficacy of Orforglipron vs Placebo to Maintain Body Weight Reduction After Treatment With Tirzepatide (Cohort 1)?
For the primary objective, using the modified treatment-regimen estimand, participants who achieved a body weight plateau with tirzepatide in SURMOUNT-5 maintained 74.7% of their body weight reduction after transitioning to orforglipron compared with 49.2% with placebo at week 52 (p<.001; Primary and Key Secondary Efficacy Endpoints for Cohort 1 in ATTAIN-MAINTAIN (Modified Treatment-Regimen Estimand)).2
In the same patient population for the modified treatment-regimen estimand, the proportion of participants at week 52 who maintained ≥80% of the body weight reduction achieved during SURMOUNT-5 was
- 43.7% with orforglipron, and
- 16.4% with placebo (p<.001; Primary and Key Secondary Efficacy Endpoints for Cohort 1 in ATTAIN-MAINTAIN (Modified Treatment-Regimen Estimand)).2
Please refer to Primary and Key Secondary Efficacy Endpoints for Cohort 1 in ATTAIN-MAINTAIN (Modified Treatment-Regimen Estimand) for additional key secondary endpoints for the modified treatment-regimen estimand.
Parameter at week 52, % (SEM) |
Cohort 1 (TZP group from SURMOUNT-5) |
||
OFG |
PBO |
OFG vs PBO |
|
In participants who achieved body weight plateau in SURMOUNT-5a |
|||
Maintenance of body weight reduction in SURMOUNT-5 |
74.7 (4.05) |
49.2 (3.92) |
ETD (95% CI) |
Participants maintaining ≥80% of body weight reduction achieved during SURMOUNT-5 |
43.7 (4.98) |
16.4 (4.60) |
Risk difference = 27.3 |
In all participants |
|||
Percent maintenance of body weight reduction achieved in SURMOUNT-5 |
74.4 (3.63) |
49.7 (3.53) |
ETD (95% CI) |
Mean percent change in body weight from SURMOUNT-5 baselineb |
-16.5 (0.90) |
12.6 (0.91) |
ETD (95% CI) |
Abbreviations: ETD = estimated treatment difference; OFG = orforglipron; PBO = placebo; SEM = standard error of the mean; TZP = tirzepatide.
Notes: p<.001 (two-sided) for superiority vs placebo, adjusted for multiplicity at week 52.
aBody weight plateau was defined as <5% body weight change from weeks 60 to 72 in the SURMOUNT-5 study.
bModel-based estimate.
Additional sensitivity analyses, based on the efficacy estimand, evaluated body weight changes from the start of SURMOUNT-5 to the end of ATTAIN-MAINTAIN for participants who received tirzepatide followed by orforglipron.2
As shown in Absolute Weight Over Time From SURMOUNT-5 to ATTAIN-MAINTAIN in Participants Switched From Tirzepatide to Orforglipron (Efficacy Estimand), participants on tirzepatide (cohort 1) randomized only to orforglipron in ATTAIN-MAINTAIN had a mean body weight of
- 115.8 kg at SURMOUNT-5 baseline
- 90.9 kg at the start of ATTAIN-MAINTAIN, and
- 95.9 kg at the end of ATTAIN-MAINTAIN (week 52, model-based estimate [MBE]).2
From the beginning of SURMOUNT-5 to the end of ATTAIN-MAINTAIN, these participants (ie, switched from tirzepatide to orforglipron) had
- a mean MBE body weight reduction of 16.8%, and
- an absolute body weight reduction of 19.6 kg.2
This represents a difference in percent weight changes of approximately 5% and an average difference in weight of approximately 5 kg from baseline.2
Figure 2 description: Among cohort 1 participants randomized only to orforglipron in ATTAIN-MAINTAIN, the mean body weight was 115.8 kg at baseline in SURMOUNT-5. At the beginning of ATTAIN-MAINTAIN, participants had a mean body weight of 90.9 kg and a mean body weight, based on model-based estimate, of 95.9 kg at week 52.
Notes: Data analyzed using the efficacy estimand. Data presented in line plots are observed mean (SEM). Data for 52ᵃ are MBE (SEM) for the mean actual value of body weight based on MMRM analysis. Dashes beginning at week 24 include participants eligible for rescue therapy. Data in ATTAIN-MAINTAIN after rescue orforglipron were imputed with worst value observed before start of rescue. All other data are MBE (SEM) of mITT population.
Abbreviations: BL = baseline; MBE = model-based estimate; mITT = modified intent-to-treat; MMRM = mixed model for repeated measures; MTD = maximum tolerated dose; OFG = orforglipron; SEM = standard error of the mean; TZP = tirzepatide.
In ATTAIN-MAINTAIN, participants from cohort 1 who switched from tirzepatide to orforglipron reported an average change in waist circumference from randomization of approximately 3 cm.2
Preservation of reductions in cardiometabolic risk factors such as glycated hemoglobin (HbA1c), insulin levels, fasting serum glucose, markers of lipids such as triglycerides and non-HDL, and systolic blood pressure were also observed.2
What Is the Efficacy of Orforglipron vs Placebo to Maintain Body Weight Reduction After Treatment With Semaglutide (Cohort 2)?
For the primary objective, using the modified treatment-regimen estimand, participants who achieved a body weight plateau with semaglutide in SURMOUNT 5 maintained 79.3% of body weight reduction after transitioning to orforglipron orforglipron with 37.6% with placebo at week 52 (p<.001; Primary and Key Secondary Efficacy Endpoints for Cohort 2 in ATTAIN-MAINTAIN (Modified Treatment-Regimen Estimand)).2
In the same patient population for the modified treatment-regimen estimand, the proportion of participants who maintained ≥80% of the body weight reduction achieved during SURMOUNT-5 was
- 55% with orforglipron, and
- 6.9% with placebo (p<.001; Primary and Key Secondary Efficacy Endpoints for Cohort 2 in ATTAIN-MAINTAIN (Modified Treatment-Regimen Estimand)).2
Please refer to Primary and Key Secondary Efficacy Endpoints for Cohort 2 in ATTAIN-MAINTAIN (Modified Treatment-Regimen Estimand) for additional key secondary endpoints for the modified treatment-regimen estimand.
Parameter at week 52, % (SEM) |
Cohort 2 (SEMA group from SURMOUNT-5) |
||
OFG |
PBO |
OFG vs PBO |
|
In participants who achieved body weight plateau in SURMOUNT-5a |
|||
Maintenance of body weight reduction achieved in SURMOUNT-5 |
79.3 (4.42) |
37.6 (7.46) |
ETD (95% CI) |
Participants maintaining ≥80% of body weight reduction achieved during SURMOUNT-5 |
55.0 (5.08) |
6.9 (3.77) |
Risk difference = 48.1 |
In all participants |
|||
Maintenance of body weight reduction achieved in SURMOUNT-5 |
85.9 (4.60) |
40.2 (7.87) |
ETD (95% CI) |
Change in body weight from SURMOUNT-5 baselineb |
-14.9 (0.94) |
-7.9 (0.81) |
ETD (95% CI) |
Abbreviations: ETD = estimated treatment difference; OFG = orforglipron; PBO = placebo; SEMA = semaglutide; SEM = standard error of the mean.
Notes: p<.001 (two-sided) for superiority vs placebo, adjusted for multiplicity at week 52.
aBody weight plateau was defined as <5% body weight change from weeks 60 to 72 in the SURMOUNT-5 study.
bModel-based estimate.
Additional sensitivity analyses, based on the efficacy estimand, evaluated body weight changes over time from the start of SURMOUNT-5 to the end of ATTAIN-MAINTAIN for participants who received semaglutide followed by orforglipron.2
As shown in Absolute Weight Over Time From SURMOUNT-5 to ATTAIN-MAINTAIN in Participants Switched From Semaglutide to Orforglipron (Efficacy Estimand), for the efficacy estimand, participants on semaglutide (cohort 2) randomized only to orforglipron in ATTAIN-MAINTAIN had a mean body weight of
- 113.5 kg at SURMOUNT-5 baseline
- 95.0 kg at the start of ATTAIN-MAINTAIN, and
- 95.9 kg at the end of ATTAIN-MAINTAIN (week 52, MBE).2
From the beginning of SURMOUNT-5 to the end of ATTAIN-MAINTAIN, participants treated with semaglutide and then to orforglipron for 52 weeks had a
- mean MBE body weight reduction of 15.1%, and
- absolute body weight reduction of 17.1 kg.2
This represents a difference in percent weight change of approximately 1% and an average difference in weight of approximately 1 kg from baseline.2
Figure 3 description: Among cohort 2 participants randomized only to orforglipron in ATTAIN-MAINTAIN, the mean body weight was 113.5 kg at baseline in SURMOUNT-5. At the start of ATTAIN-MAINTAIN, participants has a mean body weight of 95.0 kg and a mean body weight, based on model-based estimate, of 95.9 kg at week 52.
Notes: Data analyzed using efficacy estimand. Data presented in line plots are observed mean (SEM). Data for 52ᵃ are MBE (SEM) for the mean actual value of body weight based on MMRM analysis. Dashes beginning at week 24 include participants eligible for rescue therapy. Data in ATTAIN-MAINTAIN after rescue orforglipron were imputed with worst value observed before start of rescue. All other data are MBE (SEM) of mITT population.
Abbreviations: BL = baseline; MBE = model-based estimate; mITT=modified intent-to-treat; MMRM=mixed-model for repeated measures; MTD=maximum tolerated dose; OFG=orforglipron; SEM = standard error of the mean; Sema=semaglutide.
In ATTAIN-MAINTAIN, participants from cohort 2 who switched from semaglutide to orforglipron reported an average change in waist circumference from randomization of approximately 1 cm.2
Preservation of reductions in cardiometabolic risk factors such as glycated hemoglobin (HbA1c), insulin levels, fasting serum glucose, markers of lipids such as triglycerides and non-HDL, and systolic blood pressure were also observed.2
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What Safety Results are Available from Switching Patients from Injectable GLP-1 RA to Orforglipron?
Refer to Adverse Events in ATTAIN-MAINTAIN (Before Rescue Safety Set) for an overview of adverse events (AEs) that occurred during ATTAIN-MAINTAIN.
Across both cohorts, 4.8% to 7.3% of the participants who received orforglipron MTD discontinued the study drug due to AEs.2
Nausea, constipation, vomiting, and diarrhea were the most frequently reported AEs among patients receiving orforglipron ( Adverse Events That Emerged During Treatment and Occurred in ≥5% of Participants in Any Treatment Group in ATTAIN-MAINTAIN (Before Rescue Safety Set)).2
The overall incidence of gastrointestinal (GI) adverse events (AE) (including nausea, vomiting, or diarrhea) during the first 4 weeks of ATTAIN-MAINTAIN was
- 10.5% in cohort 1 (tirzepatide to orforglipron), and
- 9.5% in cohort 2 (semaglutide to orforglipron).2
Most of the GI AEs were mild to moderate in severity. No dose de-escalations had to be performed during the first 4 weeks in patients switching directly from tirzepatide or semaglutide to orforglipron 9 mg.2,3
Serious adverse events were reported by <2% of participants across both cohorts, including
- 3 participants in the orforglipron group in cohort 1, and
- 1 participant each in the orforglipron and placebo group in cohort 2 ( Adverse Events That Emerged During Treatment and Occurred in ≥5% of Participants in Any Treatment Group in ATTAIN-MAINTAIN (Before Rescue Safety Set)).2
No liver safety signals were detected. One death occurred during the study, in the orforglipron group in cohort 2, but was not considered related to the study treatment.2
Adverse event |
Cohort 1 (TZP to OFG) |
Cohort 2 (SEMA to OFG) |
||
OFG (N=124) |
PBO (N=80) |
OFG (N=105) |
PBO (N=66) |
|
Any AE emerging during treatment |
85 (68.5) |
47 (58.8) |
65 (61.9) |
35 (53.0) |
Deathsa |
0 |
0 |
1 (1.0) |
0 |
SAEs |
3 (2.4) |
0 |
1 (1.0) |
1 (1.5) |
AEs leading to discontinuation of study treatment |
9 (7.3) |
2 (2.5) |
5 (4.8) |
2 (3.0) |
Gastrointestinal disorders leading to discontinuation of study treatment |
3 (2.4) |
0 |
1 (1.0) |
0 |
AEs of special interest emerging during treatment |
||||
0 |
0 |
0 |
1 (1.5) |
|
Malignanciesb |
1 (0.8) |
0 |
0 |
0 |
Pancreatitis (adjudication-confirmed) |
1 (0.8) |
0 |
0 |
0 |
MACE (adjudication-confirmed)b |
0 |
0 |
1 (1.0) |
0 |
Cardiac disordersd |
0 |
0 |
0 |
0 |
Gastrointestinal eventsb |
3 (2.4) |
0 |
2 (1.9) |
1 (1.5) |
Gallbladder diseaseb |
0 |
0 |
0 |
0 |
Acute renal eventsb |
0 |
0 |
0 |
0 |
Major depressive disorder/suicidal ideation or behaviorb |
0 |
0 |
0 |
0 |
Hypersensitivityb |
0 |
0 |
0 |
0 |
Other AEs emerging during treatment |
||||
Cholelithiasis |
1 (0.8) |
0 |
0 |
1 (1.5) |
Abbreviations: AE = adverse event; ALT = alanine aminotransferase; AST = aspartate aminotransferase; MACE = major adverse cardiovascular event; OFG = orforglipron; PBO = placebo; SAE = serious adverse event; SEMA = semaglutide; TZP = tirzepatide.
Notes: Data are number of participants (%). Safety endpoints were evaluated using the Safety Analysis Set before rescue (SAS-Before Rescue), which included data from all participants who were randomly assigned to the study and had received at least one dose of the study intervention. Data obtained after rescue were excluded.
aCause of death was reported as follows: cardiovascular/stroke in cohort 2 participant randomized to orforglipron; Deaths were also counted as SAEs and discontinuation due to AEs.
bEvents that were classified as severe AEs or SAEs.
cDefined as elevated transaminases, bilirubin, gamma-glutamyl transferase, AST, ALT, liver function or hepatic steatosis by study investigator.
dEvents that were classified as severe or serious arrhythmias and cardiac conduction disorders.
Adverse Event |
OFG |
PBO |
Cohort 1 (TZP to OFG) |
N=124 |
N=80 |
Constipation |
15 (12.1) |
4 (5.0) |
Nausea |
29 (23.4) |
4 (5.0) |
Diarrhea |
9 (7.3) |
9 (11.2) |
Vomiting |
14 (11.3) |
1 (1.2) |
Fatigue |
7 (5.6) |
0 |
Upper respiratory tract infection |
8 (6.5) |
4 (5.0) |
Abdominal distension |
7 (5.6) |
5 (6.2) |
Hypertension |
3 (2.4) |
4 (5.0) |
Influenza |
4 (3.2) |
5 (6.2) |
Flatulence |
2 (1.6) |
5 (6.2) |
Cohort 2 (SEMA to OFG) |
N=105 |
N=66 |
Constipation |
15 (14.3) |
2 (3.0) |
Nausea |
14 (13.3) |
2 (3.0) |
Diarrhea |
8 (7.6) |
2 (3.0) |
Vomiting |
5 (4.8) |
4 (6.1) |
Upper respiratory tract infection |
8 (7.6) |
7 (10.6) |
Headache |
8 (7.6) |
1 (1.5) |
Increased appetite |
1 (1.0) |
4 (6.1) |
Abbreviations: OFG = orforglipron; PBO = placebo; SEMA = semaglutide; TZP = tirzepatide.
Notes: Data are number of participants (%). Safety endpoints were evaluated using the Safety Analysis Set before rescue (SAS-Before Rescue), which included data from all participants who were randomly assigned to the study and had received at least one dose of the study intervention. Data obtained after rescue were excluded.
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Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Foundayo [package insert]. Indianapolis, IN: Eli Lilly and Company; 2026.
2Aronne LJ, Horn DB, Le Roux CW, et al. Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial. Nat Med. Published online May 12, 2026. https://doi.org/10.1038/s41591-026-04386-7
3Ma X, Li YG, Raha S, et al. Pharmacokinetic bioequivalence of orforglipron tablets and capsules in healthy participants with obesity or overweight. Diabetes Obes Metab. Published online April 17, 2026. https://doi.org/10.1111/dom.70783
4Aronne LJ, Horn DB, le Roux CW, et al; SURMOUNT-5 Trial Investigators. Tirzepatide as compared with semaglutide for the treatment of obesity. N Engl J Med. 2025;393:26-36. https://www.doi.org/10.1056/NEJMoa2416394
Appendix
SURMOUNT-5 Study Overview
SURMOUNT-5 (NCT05822830) was a 72-week, multi-center, randomized, open-label, phase 3b trial evaluating the efficacy and safety of tirzepatide compared with semaglutide in adults with obesity, or overweight with at least one of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea (OSA) or cardiovascular disease, who did not have diabetes.4
Participants in both treatment groups received counseling on a reduced-calorie diet and increased physical activity. The trial randomized 751 participants across the US and Puerto Rico in a 1:1 ratio to receive maximum tolerated dose (MTD) of tirzepatide (10 mg or 15 mg) or semaglutide (1.7 mg or 2.4 mg). With tirzepatide, 89.3% received at least one dose of the 15 mg dose and with semaglutide 92.8% received at least one dose of the 2.4 mg dose.4
The primary objective of the study was to demonstrate tirzepatide’s superiority in percentage change from baseline in body weight at 72 weeks compared to semaglutide. 4
In the SURMOUNT-5 trial, participants treated with tirzepatide achieved an average weight reduction of 20.2% compared to 13.7% with semaglutide at 72 weeks.4
Date of Last Review: May 07, 2026