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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.
In ATTAIN-2, how did Foundayo™ (orforglipron) compare with placebo in adults with obesity or overweight and type 2 diabetes?
At week 72 (treatment-regimen estimand), orforglipron 5.5, 9, and 17.2 mg reduced body weight by 5.1% to 9.6% vs 2.5% with placebo. HbA1c reduced by 1.22% to 1.66% vs 0.47% with placebo. Orforglipron’s safety was consistent with injectable GLP-1 RAs.
See important safety information, including boxed warning, in the attached prescribing information.
Content Overview
ATTAIN-2 Overview
ATTAIN-2 is a phase 3, 72-week, randomized, double-blind, placebo-controlled trial comparing the efficacy and safety of orforglipron as monotherapy with placebo in adults with obesity or overweight and type 2 diabetes (T2D).1
This study was conducted with an investigational orforglipron capsule formulation and compared doses of 1 mg, 3 mg, 6 mg, 12 mg, 24 mg, and 36 mg with placebo.1
This response presents efficacy and safety data ffrom the investigational orforglipron capsule formulation 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.2
Study Design
The ATTAIN-2 trial randomized 1613 participants across Argentina, Australia, Brazil, China, Czech Republic, Germany, Greece, India, Republic of Korea, and the United States in a 2:1:1:1 ratio to receive either
During the study, orforglipron was administered once daily without restrictions on food and water intake.1,3
ATTAIN-2 Study Design Overview presents an overview of the study design, including the different treatment arms and dose escalation strategy for orforglipron.
Figure 1 description: ATTAIN-2 was a phase 3, 72-week, double-blind, placebo-controlled trial that randomized 1613 adults with obesity or overweight and type 2 diabetes in a 2:1:1:1 ratio to receive placebo or orforglipron (5.5 mg, 9 mg, or 17.2 mg) once daily. Orforglipron-treated participants followed a dose escalation regimen (starting at 0.8 mg and increasing every 4 weeks to 2.5 mg, 5.5 mg, 9 mg, 14.5 mg, and 17.2 mg as applicable) until the assigned dose was reached. Dose reduction was allowed if gastrointestinal symptoms persisted despite mitigations. Participants received individualized counseling healthy diet and physical activity, with emphasis on mindful eating, portion control, fiber-rich foods, and culturally and personally tailored choices.
Abbreviations: OFG = orforglipron; PBO = placebo; QD = once daily.
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Key Inclusion and Exclusion Criteria
Key inclusion and exclusion criteria for the ATTAIN-2 study are presented in Key Inclusion and Exclusion Criteria in ATTAIN-2.
Key Inclusion Criteria |
Key Exclusion Criteria |
|
|
Abbreviations: BMI = body mass index; DDP-4 = dipeptidyl peptidase-4; eGFR = estimated glomerular filtration rate; GLP-1 = glucagon-like peptide-1; HbA1c = glycated hemoglobin; MEN-2 = multiple endocrine neoplasia syndrome type 2; MTC = medullary thyroid cancer; OAM = oral antihyperglycemic medication; T1D = type 1 diabetes; T2D = type 2 diabetes.
aFor example, laser photocoagulation or intravitreal injections of anti-vascular endothelial growth factor inhibitors.
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Baseline Demographics and Clinical Characteristics of Participants
In the ATTAIN-2 study, baseline demographics and clinical characteristics were similar between orforglipron and placebo treatment groups. At baseline, participants had a mean
- age of 56.8 years
- body weight of 101.4 kg
- body mass index (BMI) of 35.6 kg/m2, and
- glycated hemoglobin (HbA1c) of 8.05%.1
Furthermore, at baseline, participants had a median duration of
- obesity of 15.9 years, and
- diabetes of 6.9 years.1
In the overall study population, 46.9% of enrolled participants were female.1
In the overall study population, 224 (13.9%) of participants were treated with sulfonylureas and 517 (32.1%) participants were treated with SGLT-2 inhibitors.1
More information on baseline demographics and clinical characteristics of participants in the ATTAIN-2 study can be found in the Appendix .
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Discontinuations
A total of 1444 (89.5%) participants completed the ATTAIN-2 study, and 1284 (79.6%) participants completed the study treatment throughout the 72-week treatment period.1
The most common reasons for treatment discontinuations were withdrawal by subject (due to personal reasons not related to the trial, scheduling conflicts, or relocation to another part of the country) and adverse events. The proportion of participants who discontinued treatment due to adverse events was between
- 6.1% and 9.9% for the orforglipron treatment groups, and
- 4.1% in the placebo group.1
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Efficacy Results
Efficacy Estimand and Treatment-Regimen Estimand
Two statistical estimands, efficacy or treatment-regimen, were used to evaluate efficacy data in ATTAIN-2.
- The treatment-regimen estimand represents the estimated average treatment effect regardless of adherence to study intervention or initiation of prohibited weight management treatments (or glycemic rescue therapy for glycemic endpoints only)
- The efficacy estimand represents efficacy had all randomized participants remained on study intervention (with possible dose interruptions and/or modifications) for 72 weeks without initiating prohibited weight management treatments (and glycemic rescue therapy for glycemic endpoints only).1
The treatment-regimen estimand was the primary estimand, with the efficacy estimand considered supportive. There was no adjustment for multiple comparisons between estimands, nor for any other analyses beyond the primary and key secondary objectives.1
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Weight-Related Primary and Key Secondary Endpoint Results
The primary objective of the study was to demonstrate that orforglipron (5.5 mg, 9 mg, 17.2 mg) is superior to placebo in the mean percent change in body weight from baseline at 72 weeks.1,2
In ATTAIN-2, treatment with orforglipron met the primary endpoint of superior body weight reduction compared with placebo.1
At week 72, for the treatment-regimen estimand, mean percent change from baseline in body weight was
- -5.1% with orforglipron 5.5 mg
- -7.0% with orforglipron 9 mg
- -9.6% with orforglipron 17.2 mg, and
- -2.5% with placebo (p<.001 for all orforglipron doses vs placebo; Treatment-Regimen and Efficacy Estimand for Weight-Related Primary and Secondary Efficacy Endpoints in ATTAIN-2).1,2
Percent change in body weight over time for the efficacy estimand is presented in Percent Change in Body Weight From Baseline To Week 72 in ATTAIN-2.
Figure description: In ATTAIN-2, percent change from baseline in body weight at week 72 was -5.5%, -7.8%, and -10.5% with orforglipron 5.5 mg, 9 mg, and 17.2 mg, respectively, and -2.2% with placebo.
Abbreviations: ETD = estimated treatment difference; MMRM = mixed model for repeated measures; OFG = orforglipron; PBO = placebo.
Notes: Data are presented as model-based estimates (95% CI), along with ETD (95% CI) between orforglipron groups and placebo based on MMRM analysis (efficacy estimand). The curves shown from week 0 to week 72 are based on observed mean with standard errors using the efficacy estimand datapoints set, including all datapoints obtained during the treatment period and up to the earliest date of discontinuation of study treatment or initiation of prohibited weight management treatments.
***p<.0001 vs placebo, adjusted for multiplicity at week 72.
Key secondary endpoints at week 72 related to body weight and adjusted for multiplicity included the percentage of participants with body weight reduction thresholds of
As presented in Treatment-Regimen and Efficacy Estimand for Weight-Related Primary and Secondary Efficacy Endpoints in ATTAIN-2, all weight-related key secondary endpoints were met in the ATTAIN-2 study.1
|
Treatment-Regimen Estimand |
Efficacy Estimand |
||||||
Parametera |
OFG 5.5 mg |
OFG 9 mg |
OFG 17.2 mg |
Placebo |
OFG 5.5 mg |
OFG 9 mg |
OFG 17.2 mg |
Placebo |
Primary endpoint: body weight, kg |
||||||||
Baseline |
102.3 |
102.7 |
99.8 |
101.2 |
102.3 |
102.7 |
99.8 |
101.2 |
Change in body weight from baseline, % |
-5.1 |
-7.0 |
-9.6 |
-2.5 |
-5.5 |
-7.8 |
-10.5 |
-2.2 |
ETD vs placebo (95% CI) |
-2.7 (-3.7, -1.6)* |
-4.5 (-5·5, -3·6)* |
-7.1 (-8.2, -6.1)* |
NA |
-3.3 (-4.1, -2.5)* |
-5.6 (-6.5, -4.7)* |
-8.3 (-9.3, -7.3)* |
NA |
Secondary endpoint: proportion of participants with weight reduction threshold at week 72, % |
||||||||
≥5% |
47.7* |
54.6* |
67.2* |
26.6 |
49.8* |
60.2* |
72.8* |
24.4 |
≥10% |
22.6* |
31.2* |
45.6* |
9.0 |
23.9* |
35.5* |
50.1* |
7.0 |
≥15%b |
6.8 |
14.4* |
26.0* |
3.0 |
7.3 |
17.7* |
28.4* |
1.9 |
Abbreviations: ANCOVA = analysis of covariance; ETD = estimated treatment difference; MMRM= mixed model for repeated measures; NA = not applicable; OFG = orforglipron.
Notes: *p<.001 (two-sided) for superiority vs placebo, adjusted for multiplicity at week 72.
aData are presented as model-based estimates for changes from baseline to week 72, along with ETD (95% CI) between the OFG groups and placebo based on ANCOVA analysis (treatment-regimen estimand) and MMRM analysis (efficacy estimand). The CIs have not been adjusted for multiplicity and should not be used for hypothesis testing. For the percentage of participants with efficacy thresholds at week 72, data are presented as model-based estimate from logistic regression. Percentages were calculated by combining the percentages of participants who met the target in imputed data sets with the use of Rubin’s rules.
bPercentage of participants with weight reduction threshold ≥15% for OFG 5.5 mg vs placebo was not a key secondary endpoint. This endpoint was not adjusted for multiplicity and p values were not included for this endpoint.
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Secondary Endpoint Results Related to Glycemic Control
Key secondary endpoints at week 72 related to glycemic control and adjusted for multiplicity included
- mean change in HbA1c on all orforglipron doses
- percentage of participants with HbA1c threshold of <7% and ≤6.5% on all orforglipron doses, and
- mean change in fasting serum glucose (FSG) on all orforglipron doses.1
At week 72, for the treatment-regimen estimand, mean change from baseline in HbA1c were
- -1.22% with orforglipron 5.5 mg
- -1.50% with orforglipron 9 mg
- -1.66% with orforglipron 17.2 mg, and
- -0.47% with placebo (p<.001 for all doses vs placebo; Treatment-Regimen and Efficacy Estimand for Glycemia-Related Secondary Efficacy Endpoints in ATTAIN-2).1,2
Mean change in HbA1c over time for the efficacy estimand is presented in HbA1c Changes Over Time in ATTAIN-2.1
Please refer to Treatment-Regimen and Efficacy Estimand for Glycemia-Related Secondary Efficacy Endpoints in ATTAIN-2 for changes in FSG from baseline to week 72 and efficacy results for the efficacy estimand.
Figure description: In ATTAIN-2, change from baseline in HbA1c at week 72 was -1.29%, -1.60%, and -1.79% with orforglipron 5.5 mg, 9 mg, and 17.2 mg, respectively, and -0.14% with placebo.
Notes: Data are presented as model-based estimates (95% CI), along with ETD (95% CI) between orforglipron groups and placebo based on MMRM analysis (efficacy estimand). The curves shown from week 0 to week 72 are based on observed mean with standard errors using the efficacy estimand datapoints set, including all datapoints obtained during the treatment period and up to the earliest date of discontinuation of study treatment or initiation of prohibited weight management treatments or glycemic rescue therapy, including prohibited glycemic therapy.
Abbreviations: ETD = estimated treatment difference; HbA1c = glycated hemoglobin; MMRM = mixed model for repeated measures; OFG = orforglipron; PBO = placebo.
|
Treatment-Regimen Estimand |
Efficacy Estimand |
||||||
Parametera |
OFG 5.5 mg |
OFG 9 mg |
OFG 17.2 mg |
Placebo |
OFG 5.5 mg |
OFG 9 mg |
OFG 17.2 mg |
Placebo |
HbA1c, % |
||||||||
Baseline |
8.03 |
8.08 |
8.05 |
8.03 |
8.03 |
8.08 |
8.05 |
8.03 |
Change in HbA1c from baseline |
-1.22 |
-1.50 |
-1.66 |
-0.47 |
-1.29 |
-1.60 |
-1.79 |
-0.14 |
ETD vs placebo (95% CI) |
-0.76 (-0.93, -0.58)* |
1.03 (-1.19, -0.87)* |
-1.20 (-1.35, -1.04)* |
NA |
-1.16 (-1.34, -0.98)* |
1.46 (-1.62, -1.30)* |
-1.65 (-1.82, -1.49)* |
NA |
Proportion of participants with HbA1c threshold at week 72, % |
||||||||
<7% |
64.6* |
75.9* |
75.5* |
30.5 |
70.0* |
78.0* |
85.1* |
23.0 |
≤6.5% |
52.5* |
57.6* |
66.6* |
15.4 |
56.2* |
67.5* |
75.0* |
10.6 |
<5.7%b |
6.6 |
15.7 |
23.7 |
1.6 |
7.8 |
17.9 |
28.1 |
0.7 |
FSG, mg/dL |
||||||||
Baseline |
152.9 |
155.1 |
154.7 |
151.5 |
152.9 |
155.1 |
154.7 |
151.5 |
Change in FSG from baseline |
-30.5 |
-38.6 |
-42.4 |
-9.3 |
-33.0 |
-41.1 |
-45.8 |
1.2 |
ETD vs placebo (95% CI) |
-21.2 (-26.8, -15.6)* |
-29.2 (-34.2, -24.3)* |
33.1 (-38.3, -27.8)* |
NA |
-34.2 (-39.8, -28.6)* |
-42.3 (-47.3, -37.3)* |
-47.0 (-52.1, -41.9)* |
NA |
FSG, mmol/L |
||||||||
Baseline |
8.5 |
8.6 |
8.6 |
8.4 |
8.5 |
8.6 |
8.6 |
8.4 |
Change in FSG from baseline |
-1.7 |
-2.1 |
-2.4 |
-0.5 |
-1.8 |
-2.3 |
-2.5 |
0.1 |
ETD vs placebo (95% CI) |
-1.2 (-1.5, -0.9)* |
-1.6 (-1.9, -1.4)* |
-1.8 (-2.1, -1.5)* |
NA |
-1.9 (-2.2, -1.6)* |
-2.4 (-2.6, -2.1) |
-2.6 (-2.9, -2.3) |
NA |
Abbreviations: ANCOVA = analysis of covariance; ETD = estimated treatment difference; FSG = fasting serum glucose; HbA1c = glycated hemoglobin; MMRM=mixed model for repeated measures; NA = not applicable; OFG = orforglipron.
Notes: *p<.001 (two-sided) for superiority vs placebo, adjusted for multiplicity at week 72.
aData are presented as model-based estimates for changes from baseline to week 72, along with ETD (95% CI) between the OFG groups and placebo based on ANCOVA analysis (treatment-regimen estimand) and MMRM analysis (efficacy estimand). The CIs have not been adjusted for multiplicity and should not be used for hypothesis testing. For the percentage of participants with efficacy thresholds at week 72, data are presented as model-based estimate from logistic regression. Percentages were calculated by combining the percentages of participants who met the target in imputed data sets with the use of Rubin’s rules.
bPercentage of participants with HbA1c threshold <5.7% for all orforglipron doses vs placebo was not a key secondary endpoint. This endpoint was not adjusted for multiplicity and p values were not included for this endpoint.
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Cardiometabolic-Related Secondary Endpoint Results
Cardiometabolic-related multiplicity-adjusted secondary endpoints measured at week 72 for the pooled orforglipron doses included the mean change in
- systolic blood pressure (SBP)
- non-HDL cholesterol, and
- triglycerides.1
Furthermore, the mean change in waist circumference on orforglipron 17.2 mg was a multiplicity-adjusted secondary endpoint in the ATTAIN-2 study.1,2
At week 72, for the treatment-regimen estimand, pooled orforglipron doses led to
- -4.2 mm Hg change in SBP compared to -1.6 mmHg with placebo (p<.001 vs placebo)
- -6.2% change in non-HDL cholesterol compared to -2.5% with placebo (p<.05 vs placebo), and
- -16.0% change in triglycerides compared to -4.2% with placebo (p<.001 vs placebo).1
Orforglipron 17.2 mg led to a -8.3 cm change in waist circumference compared to -2.8 cm with placebo (p<.001 vs placebo).1,2
Please refer to Treatment-Regimen and Efficacy Estimand for Cardiometabolic-Related Secondary Efficacy Endpoints in ATTAIN-2 for more information.1
|
Treatment-Regimen Estimand |
Efficacy Estimand |
||||||||
Parametera |
OFG 5.5 mg |
OFG 9 mg |
OFG 17.2 mg |
Pooled OFG |
Placebo |
OFG 5.5 mg |
OFG 9 mg |
OFG 17.2 mg |
Pooled OFG |
Placebo |
SBP, mm Hg |
||||||||||
Baseline |
131.3 |
132.1 |
132.5 |
132.0 |
130.6 |
131.3 |
132.1 |
132.5 |
132.0 |
130.6 |
Change in SBP from baseline |
-4.0 |
-4.2 |
-4.5 |
-4·2 |
-1.6 |
-4.3 |
-4.5 |
-5.8 |
-4.9 |
-1.5 |
ETD vs placebo (95% CI)b |
-2.4 (-4.2, -0.6) |
2.6 (-4.4, -0.9) |
-2.9 (-4.7, -1.0) |
-2.6 (-4.0, -1.3)* |
NA |
-2.9 (-4.6, -1.2) |
-3.1 (-4.8, -1.3) |
-4.4 (-6.2, -2.6) |
-3.4 (-4.8, -2.1)* |
NA |
Non-HDL cholesterol, mg/dL |
||||||||||
Baseline |
120.7 |
121.4 |
121.2 |
121.1 |
122.3 |
120.7 |
121.4 |
121.2 |
121.1 |
122.3 |
Change in non-HDL cholesterol from baseline, % |
-4.4 |
-4.4 |
-9.8 |
-6.2 |
-2.5 |
-4.6 |
-6.2 |
-8.4 |
-6.4 |
-3.0 |
ETD vs placebo (95% CI)b |
-1.9 (-5.9, 2.2) |
-1.9 (-5.6, 2.0) |
-7.4 (-11.0, -3.7) |
-3.8 (-6.6, -0.8)** |
NA |
-1.7 (-5.7, 2.4) |
-3.3 (-7.0, 0.5) |
-5.7 (-9.3, -1.8) |
-3.6 (-6.4, -0.6)** |
NA |
Triglycerides, mg/dL |
||||||||||
Baseline |
157.4 |
164.4 |
157.2 |
159.6 |
162.8 |
157.4 |
164.4 |
157.2 |
159.6 |
162.8 |
Change in triglycerides from baseline, % |
-13.5 |
-14.7 |
-19.6 |
-16.0 |
-4.2 |
-15.3 |
-16.0 |
-21.3 |
-17.6 |
-4.7 |
ETD vs placebo (95% CI)b |
-9.7 (-14.7, -4.4) |
-10.9 (-15.5, -6.0) |
-16.1 (-20.5, -11.4) |
-12.2 (-15.9, -8.4)* |
NA |
-11.2 (-16.1, -6.0) |
-11.9 (-16.8, -6.7) |
-17.4 (-22.0, -12.6) |
-13.5 (-17.2, -9.7)* |
NA |
Waist circumference, cm |
||||||||||
Baseline |
116.8 |
116.2 |
114.7 |
NA |
115.0 |
116.8 |
116.2 |
114.7 |
NA |
115.0 |
Change in waist circumference from baseline |
-5.4 |
-6.3 |
-8.3 |
NA |
-2.8 |
-5.6 |
-7.2 |
-9.2 |
NA |
-2.7 |
ETD vs placebo (95% CI)c |
-2.6 (-3.6, -1.5) |
-3.5 (-4.5, -2.5) |
5.5 (-6.5, -4.5)* |
NA |
NA |
-3.0 (-3.9, -2.1) |
-4.5 (-5.4, -3.5) |
-6.5 (-7.5, -5.5)* |
NA |
NA |
Abbreviations: ANCOVA = analysis of covariance; ETD = estimated treatment difference; HDL = high-density lipoprotein; SBP = systolic blood pressure; MMRM=mixed model for repeated measures; NA = not applicable; OFG = orforglipron.
*p<.001; **p<.05 vs placebo, adjusted for multiplicity at week 72.
aData are presented as model-based estimates for changes from baseline to week 72, along with ETD (95% CI) between the OFG groups and placebo based on ANCOVA analysis (treatment-regimen estimand) and MMRM analysis (efficacy estimand). The CIs have not been adjusted for multiplicity and should not be used for hypothesis testing.
bChange from baseline to week 72 in SBP, non-HDL cholesterol, and triglyceride for orforglipron 5.5 mg, 9 mg, or 17.2 mg vs placebo were not key secondary endpoints. These endpoints were not adjusted for multiplicity and p values were not included for these endpoints.
cChange from baseline to week 72 in waist circumference for orforglipron 5.5 mg and 9 mg vs placebo were not key secondary endpoints. These endpoints were not adjusted for multiplicity and p values were not included for these endpoints.
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Safety Results
The overall safety profile of orforglipron in ATTAIN-2 was consistent with
- the established glucagon-like peptide-1 (GLP-1) receptor agonist class, and
- findings from previous phase 3 orforglipron clinical studies.1
There was no imbalance between the orforglipron and placebo treatment groups in the overall incidence of reported adverse events (AEs).1
The most commonly reported AEs were gastrointestinal-related and generally mild to moderate in severity. These events occurred more commonly in orforglipron treatment groups mainly during dose escalation.1
An overview of AEs and AEs that occurred in ≥5% of participants are presented in Overview of Adverse Events in ATTAIN-2 and TEAEs Occurring in ≥5% of Participants in ATTAIN-2.
Adverse Eventa |
OFG 5.5 mg |
OFG 9 mg |
OFG 17.2 mg |
Placebo |
Overall |
Participants with ≥1 TEAE |
270 (82.3) |
290 (87.6) |
284 (88.5) |
545 (86.8) |
1389 (86.4) |
Serious AEs |
24 (7.3) |
34 (10.3) |
35 (10.9) |
55 (8.8) |
148 (9.2) |
Deathsb |
0 (0.0) |
4 (1.2) |
2 (0.6) |
4 (0.6) |
10 (0.6) |
AEs leading to discontinuation of study drug |
20 (6.1) |
35 (10.6) |
34 (10.6) |
29 (4.6) |
118 (7.3) |
Nausea |
2 (0.6) |
8 (2.4) |
6 (1.9) |
0 (0.0) |
16 (1.0) |
Vomiting |
5 (1.5) |
5 (1.5) |
4 (1.2) |
0 (0.0) |
14 (0.9) |
Diarrhea |
2 (0.6) |
5 (1.5) |
3 (0.9) |
1 (0.2) |
11 (0.7) |
Abdominal pain |
0 (0.0) |
1 (0.3) |
1 (0.3) |
1 (0.2) |
3 (0.2) |
Abbreviations: AE = adverse event; OFG = orforglipron; TEAE = treatment-emergent adverse event.
Notes: Includes data from all participants who were randomly assigned to the study and had at least one dose of study intervention.
aData are n (%).
bDeaths are also included as serious AEs and discontinuations due to AEs. One of the deaths in the 17.2 mg group was due to cardiopulmonary arrest. For the other 5 deaths in the orforglipron groups (4 in the 9 mg group and 1 in the 17.2 mg group), the cause was undetermined. In all these cases, either no autopsy was conducted or autopsy data were not available, and no further information regarding the cause of death was available. In the placebo group, 1 death was due to myocardial infarction, and 3 others had noncardiovascular causes.
Adverse Eventa |
OFG 5.5 mg |
OFG 9 mg |
OFG 17.2 mg |
Placebo |
Overall |
Nausea |
66 (20.1) |
103 (31.1) |
117 (36.4) |
53 (8.4) |
339 (21.1) |
Diarrhea |
70 (21.3) |
82 (24.8) |
88 (27.4) |
94 (15.0) |
334 (20.8) |
Constipation |
58 (17.7) |
70 (21.1) |
72 (22.4) |
49 (7.8) |
249 (15.5) |
Vomiting |
42 (12.8) |
67 (20.2) |
74 (23.1) |
24 (3.8) |
207 (12.9) |
Dyspepsia |
30 (9.1) |
51 (15.4) |
35 (10.9) |
22 (3.5) |
138 (8.6) |
Decreased appetite |
27 (8.2) |
30 (9.1) |
49 (15.3) |
18 (2.9) |
124 (7.7) |
Eructation |
21 (6.4) |
38 (11.5) |
28 (8.7) |
4 (0.6) |
91 (5.7) |
Headache |
17 (5.2) |
19 (5.7) |
22 (6.9) |
33 (5.3) |
91 (5.7) |
Abdominal pain |
19 (5.8) |
20 (6.0) |
18 (5.6) |
17 (2.7) |
74 (4.6) |
Dizziness |
19 (5.8) |
11 (3.3) |
22 (6.9) |
18 (2.9) |
70 (4.4) |
Abbreviation: OFG = orforglipron; TEAE = treatment-emergent adverse event.
Notes: Includes data from all participants who were randomly assigned to the study and had at least one dose of study intervention.
aData are n (%).
There were 3 cases of adjudication-confirmed pancreatitis reported during ATTAIN-2 in
Over the 72-week treatment period in ATTAIN-2, there
- were decreases in mean alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the orforglipron treatment groups, and
- was no hepatic safety signal observed.1
In ATTAIN-2, postbaseline ALT or AST ≥3x or ≥5x times the upper limit of normal (ULN) were comparable across all treatment groups.1
A total of 4 participants (3 orforglipron-treated participants and one placebo-treated participant) had ALT or AST ≥10X ULN with one of the orforglipron-treated participants also reporting total bilirubin >2x ULN.1
All cases were related to gallbladder disease and its complications in the 3 orforglipron-treated participants.1
There were no cases of medullary thyroid cancer, and 1 case of pancreatic neoplasm (in a placebo-treated participant) was reported.1
There was 1 case of severe hypoglycemia (defined as an event characterized by altered mental status, physical status, or both that the participant was unable to resolve without assistance) reported in a participant receiving orforglipron 5.5 mg.1,2
This participant unintentionally missed their morning meal after taking study drug and metformin.1
There were 21 participants who reported level 2 hypoglycemia (blood glucose <54 mg/dL [3.0 mmol/L]) while on study treatment.1
There was a higher incidence of level 2 hypoglycemia in the orforglipron treatment groups which occurred mainly in participants taking sulfonylureas at baseline.1
At week 72, the mean pulse rate increased by
- 3.0 to 4.4 beats per minute across orforglipron groups, and
- 0 beats per minute in the placebo group.1
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Enclosed Prescribing Information
References
The published reference below is available by contacting 1-800-LillyRx (1-800-545-5979).
1Horn DB, Ryan DH, Giljanovic Kis S, et al; ATTAIN-2 Trial Investigators. Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial. Lancet. 2025;406(10522):2927-2944. https://doi.org/10.1016/S0140-6736(25)02165-8
2Foundayo [package insert]. Indianapolis, IN: Eli Lilly and Company; 2026.
3Ma X, Liu R, Pratt EJ, et al. Effect of food consumption on the pharmacokinetics, safety, and tolerability of once-daily orally administered orforglipron (LY3502970), a non-peptide GLP-1 receptor agonist. Diabetes Ther. 2024;15:819-832. https://doi.org/10.1007/s13300-024-01554-1
4Data on file, Eli Lilly and Company and/or one of its subsidiaries.
Appendix
Baseline Demographics and Clinical Characteristics
Parametera |
OFG 5.5 mg |
OFG 9 mg |
OFG 17.2 mg |
Placebo |
Age, years |
56.8 ± 10.4 |
56.2 ± 10.5 |
58.1 ± 10.8 |
56.5 ± 10.9 |
Female, n (%) |
150 (45.6) |
155 (46.7) |
154 (47.8) |
298 (47.3) |
Race or ethnic groupb, n (%) |
||||
American Indian or Alaska Native |
0 (0.0) |
2 (0.6) |
1 (0.3) |
2 (0.3) |
Asian |
58 (17.6) |
55 (16.6) |
54 (16.8) |
112 (17.8) |
Black or African American |
21 (6.4) |
19 (5.7) |
28 (8.7) |
37 (5.9) |
White |
238 (72.3) |
235 (70.8) |
228 (70.8) |
442 (70.2) |
Native Hawaiian or Other Pacific Islander |
2 (0.6) |
1 (0.3) |
0 (0.0) |
3 (0.5) |
Multiple |
5 (1.5) |
12 (3.6) |
6 (1.9) |
22 (3.5) |
Hispanic or Latino |
102 (31.0) |
95 (28.6) |
97 (30.1) |
194 (30.8) |
Duration of obesity, years |
18.7 ± 13.2 |
17.2 ± 12.0 |
18.0 ± 12.3 |
18.3 ± 12.9 |
Duration of diabetes, years |
9.3 ± 7.1 |
7.7 ± 6.3 |
9.1 ± 7.0 |
8.2 ± 6.3 |
Body weight, kg |
102.3 ± 22.7 |
102.7 ± 21.3 |
99.8 ± 23.0 |
101.2 ± 22.6 |
BMI, kg/m² |
35.9 ± 7.0 |
36.1 ± 6.3 |
35.1 ± 6.5 |
35.5 ± 6.5 |
BMI category, n (%) |
||||
<30 |
67 (20.4) |
52 (15.7) |
83 (25.8) |
124 (19.7) |
≥30 to <35 |
108 (32.8) |
111 (33.4) |
97 (30.1) |
222 (35.2) |
≥35 to <40 |
85 (25.8) |
90 (27.1) |
83 (25.8) |
151 (24.0) |
≥40 |
69 (21.0) |
79 (23.8) |
59 (18.3) |
133 (21.1) |
Waist circumference, cm |
116.8 ± 15.1 |
116.2 ± 13.4 |
114.7 ± 15.1 |
115.0 ± 14.6 |
Blood pressure, mmHg |
||||
Systolic |
131.3 ± 14.7 |
132.1 ± 15.0 |
132.5 ± 13.7 |
130.6 ± 14.1 |
Diastolic |
81.6 ± 10.4 |
82.1 ± 10.0 |
81.8 ± 10.1 |
81.0 ± 9.1 |
Pulse, bpm |
75.9 ± 11.4 |
73.7 ± 10.7 |
74.6 ± 10.5 |
74.2 ± 10.5 |
Lipid parameters, mg/dL |
||||
Total cholesterol |
173.1 ± 42.8 |
172.6 ± 45.5 |
173.6 ± 46.7 |
173.2 ± 46.2 |
Non-HDL cholesterol |
128.0 ± 43.1 |
128.5 ± 44.7 |
129.1 ± 45.7 |
129.7 ± 45.6 |
HDL cholesterol |
44.9 ± 11.4 |
44.0 ± 10.4 |
44.4 ± 11.0 |
43.4 ± 11.0 |
LDL cholesterol |
92.5 ± 37.7 |
91.3 ± 36.9 |
94.3 ± 39.9 |
93.4 ± 40.3 |
Triglycerides |
185.9 ± 151.9 |
189.4 ± 130.4 |
177.9 ± 98.4 |
189.4 ± 152.6 |
eGFRc, mL/min/1.73 m² |
82.3 ± 20.9 |
83.9 ± 21.0 |
82.2 ± 22.5 |
82.7 ± 21.5 |
HbA1c, % |
8.03 ± 0.73 |
8.08 ± 0.76 |
8.05 ± 0.73 |
8.03 ± 0.75 |
HbA1c, mmol/mol |
64.3 ± 8.0 |
64.8 ± 8.4 |
64.5 ± 8.0 |
64.3 ± 8.2 |
hsCRP, mg/L |
5.0 ± 8.4 |
5.8 ± 13.4 |
4.4 ± 9.0 |
5.5 ± 10.0 |
Antihyperglycemic drug class, n (%) |
||||
Biguanides |
282 (85.7) |
275 (82.8) |
270 (83.9) |
524 (83.2) |
Sulfonylureas |
40 (12.2) |
51 (15.4) |
50 (15.5) |
83 (13.2) |
SGLT-2 inhibitors |
105 (31.9) |
97 (29.2) |
109 (33.9) |
206 (32.7) |
Thiazolidinediones |
15 (4.6) |
14 (4.2) |
16 (5.0) |
32 (5.1) |
AGIs |
0 (0.0) |
4 (1.2) |
2 (0.6) |
4 (0.6) |
Other |
0 (0.0) |
0 (0.0) |
1 (0.3) |
2 (0.3) |
Number of oral antihyperglycemic drugs, n (%) |
||||
0 |
31 (9.4) |
35 (10.5) |
35 (10.9) |
73 (11.6) |
1 |
176 (53.5) |
172 (51.8) |
146 (45.3) |
311 (49.4) |
2 |
103 (31.3) |
106 (31.9) |
121 (37.6) |
204 (32.4) |
≥3 |
19 (5.8) |
19 (5.7) |
20 (6.2) |
42 (6.7) |
Comorbidities, n (%) |
||||
Hypertension |
252 (76.6) |
233 (70.2) |
246 (76.4) |
470 (74.6) |
Dyslipidemia |
232 (70.5) |
242 (72.9) |
225 (69.9) |
441 (70.0) |
Coronary artery disease |
19 (5.8) |
21 (6.3) |
27 (8.4) |
49 (7.8) |
Cerebrovascular disease |
14 (4.3) |
19 (5.7) |
17 (5.3) |
32 (5.1) |
Obstructive sleep apnea |
49 (14.9) |
45 (13.6) |
34 (10.6) |
86 (13.7) |
Osteoarthritis |
71 (21.6) |
57 (17.2) |
78 (24.2) |
112 (17.8) |
Anxiety or depression |
45 (13.7) |
50 (15.1) |
42 (13.0) |
86 (13.7) |
MASLD |
96 (29.2) |
100 (30.1) |
96 (29.8) |
173 (27.5) |
Asthma or COPD |
28 (8.5) |
37 (11.1) |
23 (7.1) |
48 (7.6) |
PCOS |
3 (2.0) |
1 (0.6) |
4 (2.6) |
6 (2.0) |
Gout or hyperuricemia |
36 (10.9) |
39 (11.7) |
45 (14.0) |
81 (12.9) |
Renal disease |
34 (10.3) |
37 (11.1) |
31 (9.6) |
78 (12.4) |
Number of comorbidities, n (%) |
||||
None |
16 (4.9) |
21 (6.3) |
17 (5.3) |
43 (6.8) |
1-2 |
142 (43.2) |
143 (43.1) |
145 (45.0) |
272 (43.2) |
3-4 |
124 (37.7) |
129 (38.9) |
111 (34.5) |
224 (35.6) |
≥5 |
47 (14.3) |
39 (11.7) |
49 (15.2) |
91 (14.4) |
Abbreviations: AGI = α-glucosidase inhibitor; BMI = body mass index; bpm = beats per minute; CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration; COPD = chronic obstructive pulmonary disease; eGFR = estimated glomerular filtration rate; HbA1c = glycated hemoglobin; HDL = high-density lipoprotein; hsCRP = high-sensitivity C-reactive protein; LDL = low-density lipoprotein; MASLD = metabolic dysfunction-associated steatotic liver disease; OFG = orforglipron; PCOS = polycystic ovarian syndrome; SGLT-2 = sodium-glucose cotransporter-2.
aData are mean ± SD, unless otherwise noted.
bRace or ethnicity was reported by the participants.
cThe value for eGFR was calculated according to the cystatin C-based CKD-EPI equation.
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Date of Last Review: April 01, 2026